Breast Cancer : Drug Summary | MIMS Philippines

Agent Affecting Bone Metabolism

Drug

Dosage

Remarks

Raloxifene

Risk reduction for invasive breast cancer in postmenopausal women:
60 mg PO 24 hourly

Adverse Reactions

Hot flushes, leg cramps, peripheral edema, endometrial fluid accumulation, thromboembolic events (deep venous thrombosis [DVT], pulmonary embolism)
Rare: Headache, rashes, hypertension, mild breast symptoms, GI disturbance, thrombocytopenia

Special Instructions

Contraindicated in women with history of thromboembolic disorders, hepatic and severe renal impairment
Use with caution in women with risk factors for stroke and venous thromboembolism, in moderate renal impairment

Supportive Therapy for Bone Metastasis

Drug	Dosage	Remarks
Denosumab	120 mg SC into thigh, abdomen or upper arm every 4-6 weeks	Adverse Reactions Dermatologic effects (alopecia, hyperhidrosis); Musculoskeletal effects (musculoskeletal pain, osteonecrosis of the jaw [ONJ]); Metabolic effects (hypocalcemia, hypophosphatemia); Other effects (dyspnea, diarrhea, new primary malignancy, tooth extraction) Special Instructions Calcium and vitamin D supplementation is recommended Avoid use in patients with hypocalcemia Use with caution in patients with severe renal and hepatic impairment, impaired immune system
Ibandronic acid (Ibandronate)	Prophylaxis of skeletal events in patients with breast cancer and bone metastases: 50 mg PO 24 hourly or 6 mg IV infusion over at least 15 minutes every 3-4 weeks	Adverse Reactions GI effects (dyspepsia, abdominal pain, diarrhea, nausea/vomiting); Other effects (back pain, headache) Special Instructions Calcium and vitamin D supplementation is recommended if with inadequate dietary intake Avoid in patients with severe renal impairment and disturbances of bone and mineral metabolism Consider periodic reevaluation of the need for continued therapy with bisphosphonate especially in patients who have been treated for >5 years Administer with plain water 60 minutes before first food, beverage or medication of the day; swallow the tablet whole in an upright position; do not chew, crush or suck; do not lie down for 60 minutes following administration to facilitate drug delivery to stomach and to avoid esophageal irritation
Pamidronate (Disodium pamidronate)	Osteolytic lesions and bone pain in bone metastases associated with breast cancer: 90 mg IV infusion every 4 weeks	Adverse Reactions Metabolic effects (hypocalcemia, hypophosphatemia, hypokalemia, hypomagnesemia, increased serum creatinine); CNS effects (agitation, confusion, dizziness, lethargy, insomnia, somnolence, seizures, hallucinations); CV effects (hypotension, hypertension); Hematologic effects (lymphocytopenia, thrombocytopenia, anemia); Other effects (flu-like symptoms, ONJ, femoral fractures) Special Instructions Use with caution in patients with hypercalcemia, post-thyroid surgery, cardiac disease, preexisting/at risk for renal impairment, precipitated convulsions, ONJ, musculoskeletal pain Use with caution in patients who require mental alertness (ie driving, machine operation)
Zoledronic acid (Zoledronate)	Bone metastases associated with solid tumors: 4 mg IV infusion over at least 15 minutes every 3-4 weeks	Adverse Reactions Musculoskeletal effects (increased bone pain from mineralization defect, back pain, myalgia); GI effects (diarrhea, nausea/vomiting); CNS effects (headache, dizziness); Other effects (dyspnea, depression, eye pain, hypocalcemia, fever, fatigue) Special Instructions Avoid in patients with severe renal impairment, hepatic impairment, musculoskeletal pain, ONJ, atypical fractures of the femur Use with caution in patients who require mental alertness (ie driving, machine operation), patients with Aspirin-sensitive asthma, mild-moderate renal failure

Anabolic Agent

Drug

Dosage

Remarks

Nandrolone

25-50 mg IM every 2-3 weeks

Adverse Reactions

Virilization in women, suppression of ovarian activity, atrophy of breasts and endometrial tissue, amenorrhea; Other effects (water and salt retention, edema, increased vascularity of the skin and bone growth)

Special Instructions

Use with caution in patients with renal or hepatic dysfunction, hypertension, epilepsy, migraine; diabetic patients may need dose adjustments of antidiabetic drugs
Avoid in patients with nephrosis or nephrotic phase of nephritis, cardiac and renal failure, liver disease with impaired bilirubin excretion, hepatic carcinoma, edema

Androgens & Related Synthetic Drugs

Drug

Dosage

Remarks

Fluoxymesterone

Up to 40 mg PO 24 hourly

Adverse Reactions

Amenorrhea, menstrual irregularities, gonadotropin secretion inhibition, virilization; Hepatic effects (alterations in LFTs, cholestatic jaundice); CNS effects (headache, depression, anxiety); Other effects (edema, nausea, changes in libido, hypercalcemia, acne, fluid and electrolyte retention, accelerated bone maturation, clotting factor suppression)

Special Instructions

Observe for signs of virilization
Use with caution in patients with history of severe heart, liver and kidney disease
Avoid in patients who are or may become pregnant

Cancer Hormone Therapy

Antiestrogen Agents¹
Drug	Dosage	Remarks
Elacestrant	345 mg PO 24 hourly until disease progression or unacceptable toxicity	Adverse Reactions Metabolic/endocrine effects (increased cholesterol, triglycerides, decreased sodium, hot flush); GI effects (nausea/vomiting, diarrhea, constipation, abdominal pain, dyspepsia, decreased appetite); Hepatic effects (increased AST, ALT); CNS effects (headache, fatigue); Other effects (musculoskeletal pain, decreased hemoglobin, increased creatinine) Special Instructions Take with food Avoid use in patients with severe hepatic impairment Use with caution in patients with moderate hepatic impairment Monitor lipid profile before initiating treatment and periodically thereafter
Fulvestrant	250 mg slow IM injection, 1 in each buttock on days 1, 15, 29, then once monthly thereafter	Adverse Reactions Local injection site reactions, asthenia, nausea, elevated hepatic enzymes Special Instructions Avoid in patients with severe hepatic impairment Use with caution in patients with mild to moderate hepatic impairment, severe renal impairment, bleeding diatheses, thrombocytopenia, on anticoagulants, potential risk of osteoporosis; thrombolic events in patients with advanced breast cancer
Tamoxifen	20 mg/day PO in single dose or 40 mg/day PO divided 12 hourly	Adverse Reactions CV effects (edema, chest pain, hypertension); GI effects (nausea, weight loss, diarrhea, abdominal pain); CNS effects (fatigue, dizziness, insomnia, depression); Dermatologic effects (rash, alopecia); Other effects (menstrual disorder, hot flushes, weakness, vaginal discharge, leukopenia, thrombocytopenia, hypercholesterolemia, pain) Special Instructions Use with caution in patients with history of DVT or pulmonary embolism Associated with increased risk of uterine or endometrial cancer
Toremifene	60 mg PO 24 hourly	Adverse Reactions GI effects (nausea/vomiting, constipation, loss of appetite); Respiratory effects (dyspnea, pulmonary embolism); CNS effects (fatigue, headache, dizziness, insomnia, depression, vertigo); Dermatologic effects (skin discoloration, sweating, pruritus); Gynecologic effects (vaginal discharge, endometrial changes); Other effects (abnormal vision, hot flushes, asthenia, increased weight, jaundice, thrombophlebitis) Special Instructions Use with caution in patients with uncompensated heart failure, severe angina pectoris, increased risk for endometrial cancer, bone metastases Monitor CBC, serum calcium concentration, LFTs
Enzyme Inhibitors
Anastrazole	1 mg PO 24 hourly Duration of treatment as adjuvant therapy: 5 years	Adverse Reactions GI effects (nausea/vomiting. changes in weight, abdominal pain, bowel movement changes); CNS effects (fatigue, headache, dizziness, depression); CV effects (hypertension, edema); Dermatologic effects (alopecia, rash, pruritus); Other effects (cough, dyspnea, infection, decreased bone mineral density, weakness, hot flushes, hypercholesterolemia) Special Instructions Take doses with breakfast and dinner If medication is missed for ≥3 days, restart at lowest dose and increase to current dose Treatment should be maintained at maximum tolerated dose Maintain adequate hydration Avoid in patients with severe renal or hepatic impairment Use with caution in patients with supraventricular cardiac conduction abnormalities, patients with seizures, COPD, asthma, risk of GI bleeding or in patients with bladder outlet obstruction, mild to moderate liver or renal dysfunction No dosage adjustment is needed in the elderly
Exemestane	25 mg PO 24 hourly Duration of treatment as adjuvant therapy: 5 years or until tumor relapse occurs or until with disease progression
Letrozole	2.5 mg PO 24 hourly Duration of treatment as adjuvant therapy: 5 years or until tumor relapse occurs Metastatic disease: Continue until tumor progression is evident
Gonadotropin Releasing Hormone Analogues
Goserelin	3.6 mg depot SC injection into the anterior abdominal wall every 28 days	Adverse Reactions Hypoestrogenism (transient vaginal bleeding, hot flushes, vaginal dryness, decreased libido, breast tenderness, insomnia, depression, irritability and fatigue, decreased skin elasticity, headache, osteoporosis after several weeks of treatment); GI effects (nausea, abdominal discomfort); Other effects (transient increase in menstrual bleeding, reduction in glucose tolerance can develop, changes in serum lipids and hepatic effects, hypersensitivity reactions) Special Instructions Avoid in patients with hypersensitivity to Goserelin, Leuprorelin, or other GnRH analogues Use with caution in patients with metabolic bone disease, polycystic ovarian syndrome, patients at risk of ureteric obstruction or spinal cord compression; may cause uterine cervical resistance, risk of developing ovarian hyperstimulation syndrome
Leuprorelin	3.75 mg SC/IM injection once every 28 days or 11.25 mg SC/IM once every 3 months
Triptorelin	In combination with Tamoxifen or aromatase inhibitor: 3.75 mg IM injection once every 28 days administered 6-8 weeks prior to aromatase inhibitor treatment Duration of treatment as adjuvant therapy: 5 years
Progestogens
Medroxyprogesterone acetate	400-1,500 mg/day PO or 500-1,000 mg/day IM x 28 days then 500 mg IM twice weekly	Adverse Reactions CNS effects (loss of concentration, nervousness, insomnia, somnolence, fatigue, dizziness, depression, headache); Other effects (breast tenderness, abnormal uterine bleeding, amenorrhea, prolonged anovulation, GI and hepatobiliary disorders, WBC and platelet count elevation, vision disorders) Special Instructions Use with caution in patients with cushingoid symptoms, suppressed adrenal function, diabetes and/or arterial hypertension, epilepsy, asthma, cardiac and renal dysfunction, history of mental depression Discontinue if with papilledema or retinal vascular lesion, jaundice or liver function deterioration, significant increase in BP, new onset of migraine-type headache Avoid in patients with thrombophlebitis, thromboembolic disorders, hypercalcemia with osseous metastases, impaired liver function or active liver disease, missed abortion, metrorrhagia, undiagnosed vaginal bleeding, suspected and early breast carcinoma
Megestrol acetate	160 mg PO 24 hourly x ≥2 months	Adverse Reactions Weight gain; occasionally nausea/vomiting edema, breakthrough uterine bleeding Special Instructions Use with caution in patients with history of thromboembolic disease, severe liver impairment, thrombophlebitis, galactose intolerance, glucose-galactose malabsorption, Lapp lactase deficiency Avoid in patients with hypersensitivity

¹Various antiestrogens are available. Please see the latest MIMS for specific formulations and prescribing information.

Targeted Cancer Therapy

Preoperative/Adjuvant Monotherapy Agents for Breast Cancer

Drug	Dosage	Remarks
Adotrastuzumab emtansine (TDM-1)	3.6 mg/kg IV infusion Cycled every 21 days Duration of treatment for early breast cancer: 14 cycles Metastatic disease: Continue until tumor progression or unacceptable toxicity	Adverse Reactions GI effects (dry mouth, abdominal pain, nausea/vomiting, diarrhea, constipation); CV effect (left ventricular dysfunction); CNS effects (dizziness, peripheral neuropathy, headache, insomnia); Musculoskeletal effects (pain, arthralgia, myalgia); Hematologic effects (thrombocytopenia, anemia); Respiratory effects (dyspnea, cough); Metabolic effects (increased transaminases, hypokalemia); Other effects (pyrexia, asthenia, fatigue, rash, hemorrhage, epistaxis) Special Instructions Do not administer as IV push or bolus Monitor serum transaminases, bilirubin, and platelet counts prior to initiation and at each dose Assess LVEF prior to initiation and at regular intervals during treatment Discontinue if diagnosed with interstitial lung diseases or nodular regenerative hyperplasia Bleeding with fatal outcome and peripheral neuropathy have been reported; fetal harm may occur Perform assessment of HER2 status prior to initiation of treatment
Capecitabine	1,000-1,250 mg/m² PO 12 hourly on days 1-14 Cycled every 21 days x 6-8 cycles Maintenance dose: 650 mg/m² PO 12 hourly on days 1-28 Cycled every 28 days x 1 year	Adverse Reactions GI effects (diarrhea, nausea/vomiting, abdominal pain, stomatitis, constipation, dyspepsia, flatulence); Hematologic effects (neutropenia, anemia, lymphopenia); CNS effects (anorexia, insomnia, depression, headache, dizziness); Respiratory effects (nasopharyngitis, lower respiratory tract infection, rhinorrhea, cough, dyspnea); CV effect (edema); Other effects (fatigue, hand-foot syndrome, increased blood bilirubin) Special Instructions Contraindicated in patients with severe renal/hepatic impairment, dihydropyrimidine dehydrogenase deficiency, severe leukopenia, neutropenia or thrombocytopenia Use with caution in patients with renal impairment, mild-moderate hepatic dysfunction, galactose intolerance, patients taking oral coumarin-derivative anticoagulants Monitor ALT, AST, serum electrolytes
Neratinib	240 mg PO 24 hourly continuously for up to 1 year or 120 mg PO 24 hourly on days 1-7, 160 mg PO 24 hourly on days 8-14, 240 mg PO 24 hourly on days 15-28 Cycled every 28 days for 1 cycle Followed by 240 mg PO 24 hourly on days 1-28 Cycled every 28 days for 12 cycles beginning with cycle 2	Adverse Reactions GI effects (nausea/vomiting, diarrhea, abdominal pain, stomatitis, dyspepsia, abdominal distention, decreased appetite); Dermatologic effects (nail disorder, dry skin); Other effects (fatigue, rash, decreased weight, muscle spasms, increased AST/ALT, urinary tract infection) Special Instructions To be taken with food Withhold in patients experiencing severe and/or persistent diarrhea, grade 3 liver abnormalities Discontinue in patients with grade 4 diarrhea or liver abnormalities or grade ≥2 diarrhea that occurs after maximal dose reduction Monitor LFTs
Olaparib	300 mg PO 12 hourly Cycled every 28 days for 1 year	Adverse Reactions Hematologic effects (anemia, lymphopenia, neutropenia, leukopenia, thrombocytopenia, mean corpuscular volume elevation); CNS effects (headache, dizziness); GI effects (nausea/vomiting, diarrhea, dyspepsia, upper abdominal pain, stomatitis, dysgeusia, decreased appetite); Other effects (fatigue, asthenia, increase in blood creatinine, rash) Special Instructions Use with caution in patients with moderate to severe hepatic/renal impairment, hematological toxicity, myelodysplastic syndrome/acute myeloid leukemia, pneumonitis

Monotherapy Agents for Recurrent or Metastatic Breast Cancer

Monoclonal Antibodies
Drug	Dosage	Remarks
Ado-trastuzumabemtansine (T-DM1)	3.6 mg/kg IV infusion every 3 weeks until disease progression or unacceptable toxicity First infusion: Over 90 minutes, observe patient during infusion and for at least 90 minutes for infusion-related reactions Subsequent infusions: Over 30 minutes if prior infusion well tolerated	Adverse Reactions GI effects (dry mouth, abdominal pain, nausea/vomiting, diarrhea, constipation); CV effect (left ventricular dysfunction); CNS effects (dizziness, peripheral neuropathy, headache, insomnia); Musculoskeletal effects (pain, arthralgia, myalgia); Hematologic effects (thrombocytopenia, anemia); Respiratory effects (dyspnea, cough); Metabolic effects (increased transaminases, hypokalemia); Other effects (pyrexia, asthenia, fatigue, rash, hemorrhage, epistaxis) Special Instructions Do not administer as IV push or bolus Monitor serum transaminases, bilirubin, and platelet counts prior to initiation and at each dose Assess LVEF prior to initiation and at regular intervals during treatment Discontinue if diagnosed with interstitial lung diseases or nodular regenerative hyperplasia Bleeding with fatal outcome and peripheral neuropathy have been reported; fetal harm may occur Perform assessment of HER2 status prior to initiation of treatment
Dostarlimab	500 mg IV infusion over 30 minutes every 3 weeks x 4 cycles followed by 1,000 mg every 6 weeks until disease progression or unacceptable toxicity	Adverse Reactions GI effects (nausea/vomiting, diarrhea, colitis, pancreatitis); Hematologic effects (anemia, decreased lymphocytes); Metabolic effects (decreased sodium, increased alkaline phosphatase, decreased albumin, increased transaminases, hypothyroidism); Musculoskeletal effects (arthralgia, myalgia); Other effects (pneumonitis, fatigue, asthenia, rash, pruritus, pyrexia, chills) Special Instructions Use with caution in patients with history of allogeneic hematopoietic stem cell transplantation (HSCT) Monitor for signs and symptoms of immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, rash, arthralgia) Evaluate clinical chemistries, including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment
Fam-trastuzumab deruxtecan-nxki	5.4 mg/kg IV infusion once every 3 weeks	Adverse Reactions GI effects (nausea/vomiting, constipation, diarrhea, decreased appetite); Hematologic effects (neutropenia, leukopenia, thrombocytopenia, anemia); Other effects (cough, alopecia, fatigue) Special Instructions Use with caution in patients at risk for severe, life-threatening, or fatal interstitial lung disease (ILD), severe neutropenia including febrile neutropenia, cardiac disorders Monitor CBC and assess LVEF prior to initiation and prior to each dose, and as clinically indicated
Pembrolizumab	MSI-H/MMR mutation-positive, TMB-H tumor: 200 mg by IV infusion over 30 minutes every 3 weeks or 400 mg by IV infusion over 30 minutes every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression	Adverse Reactions GI effects (nausea, constipation, decreased appetite, diarrhea); Respiratory effects (cough, pneumonitis, dyspnea, pneumonia); Dermatologic effects (pruritus, rash, cellulitis); Other effects (fatigue, arthralgia, renal failure, pain) Special Instructions Withhold treatment if any of the following occurs: Moderate pneumonitis, moderate or severe immune-mediated colitis, moderate hypophysitis, severe hyperglycemia, moderate immune-mediated nephritis Discontinue if life-threatening adverse events of pneumonitis, colitis, hypophysitis, hyperthyroidism, nephritis, infusion reactions, severe liver enzyme elevations occur Monitor liver enzymes, serum creatinine, and thyroid and renal function
Sacituzumab govitecan-hziy	10 mg/kg IV once weekly on days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity	Adverse Reactions GI effects (nausea/vomiting, diarrhea, constipation, abdominal pain, decreased appetite); Hematologic effects (anemia,neutropenia); Dermatologic effects (rash, alopecia); Other effect (fatigue) Special Instructions Use with caution in patients with reduced UGT1A1 activity Use antiemetic preventive treatment and withhold therapy for patients with grade 3 nausea or grade 3-4 vomiting at the time of scheduled treatment Monitor patients during the infusion and for at least 30 minutes after completion of infusion
Trastuzumab	Initial loading dose: 4 mg/kg 90-min IV infusion followed by 2 mg/kg 30-minutes IV infusion weekly or Initial loading dose: 8 mg/kg 90-minutes IV infusion followed by 6 mg/kg 90-minutes IV infusion 3 weeks later, then 6 mg/kg 90-minutes IV infusion at 3-weekly intervals or 600 mg SC over 2-5 minutes at 3-weekly intervals	Adverse Reactions CV effects (tachycardia, CHF); GI effects (nausea/vomiting, diarrhea, abdominal pain, anorexia); Hematologic effects (anemia, leukopenia); Musculoskeletal effects (bone pain, arthralgia, back pain); CNS effects (headache, insomnia, dizziness, paresthesia, depression, peripheral neuritis, neuropathy); Respiratory effects (cough, dyspnea, rhinitis, pharyngitis, sinusitis); Dermatologic effects (rash, acne); Other effects (infection, edema, pain, asthenia, fever, chills, flu-like illness) Special Instructions Use with caution in patients with increased cardiac risk, dyspnea, interstitial lung disease, ongoing treatment with anthracycline-based regimen Obtain baseline cardiac assessment and monitor; assess LVEF prior to initiation and at regular intervals during treatment
Protein Kinase Inhibitors
Entrectinib	NTRK Gene Fusion-Positive ≥12 years with 0.91-1.10 m² BSA: 400 mg PO 24 hourly ≥12 years with 1.11-1.50 m² BSA: 500 mg PO 24 hourly ≥12 years with >1.50 m² BSA: 600 mg PO 24 hourly Adult: 600 mg PO 24 hourly	Adverse Reactions GI effects (constipation, dysgeusia, diarrhea, nausea/vomiting); CNS effects (dizziness, cognitive impairment); Respiraotry effects (dyspnea, cough); Musculoskeletal effects (myalgia, arthralgia); Other effects (fatigue, edema, dysesthesia, increased weight, pyrexia, vision disorders) Special Instructions Use with caution in patients with new or worsening CHF, myocarditis, QT prolongation, at risk for fractures, hyperuricemia Assess LVEF, serum uric acid levels prior to initiation of therapy Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated Withhold treatment for new-onset or worsening CHF, new visual changes or changes that interfere with activities of daily living or presence of CNS effects (cognitive impairment, mood disorders, dizziness, sleep disturbances)
Larotrectinib	NTRK Gene Fusion-Positive 100 mg PO 12 hourly	Adverse Reactions GI effects (nausea/vomiting, constipation, diarrhea); CNS effects (delirium, gait disturbance, dysarthria, dizziness, paresthesia, memory impairment); Other effects (increased AST/ALT, anemia, fatigue, cough) Special Instructions Swallow capsules whole with water Use with caution in patients with hepatic impairment, women of childbearing potential Withhold or permanently discontinue if with neurologic adverse reactions
Olaparib	300 mg PO 12 hourly Cycled every 28 days	Adverse Reactions Hematologic effects (anemia, lymphopenia, neutropenia, leukopenia, thrombocytopenia, mean corpuscular volume elevation); CNS effects (headache, dizziness); GI effects (nausea/vomiting, diarrhea, dyspepsia, upper abdominal pain, stomatitis, dysgeusia, decreased appetite); Other effects (fatigue, asthenia, increase in blood creatinine, rash) Special Instructions Use with caution in patients with moderate to severe hepatic/renal impairment, hematological toxicity, myelodysplastic syndrome/acute myeloid leukemia, pneumonitis
Repotrectinib	NTRK Gene Fusion-Positive 160 mg PO 24 hourly x 14 days then increased to 160 mg PO 12 hourly until disease progression	Adverse Reactions CNS effects (dizziness, peripheral neuropathy, cognitive impairment, ataxia, fatigue); GI effects (dysgeusia, constipation, nausea); Other effects (muscular weakness, dyspnea) Special Instructions Monitor LFTs and creatine phosphokinase every 2 weeks during the first month of therapy then monthly thereafter and as clinically indicated; monitor serum uric acid before initiation then periodically during treatment Monitor for signs and symptoms of CNS toxicity and new or worsening pulmonary symptoms indicative of ILD
Selpercatinib	Rearranged during transfection (RET) gene fusion-positive tumor <50 kg: 120 mg PO 12 hourly until disease progression ≥50 kg: 160 mg PO 12 hourly until disease progression	Adverse Reactions CV effects (edema, hypertension, prolonged QT interval); GI effects (nausea, diarrhea, dry mouth, abdominal pain, constipation); CNS effects (fatigue, headache); Other effects (rash, increased AST/ALT) Special Instructions Contraindicated in patients with uncontrolled hypertension Use with caution in patients with severe hepatic impairment, risk factors for QT prolongation and tumor lysis syndrome Monitor ALT and AST prior to initiation, every 2 weeks during the first 3 months of therapy then monthly thereafter; monitor BP after 1 week of therapy and at least monthly thereafter; monitor QT interval, electrolytes and TSH at baseline and regularly during treatment
Talazoparib	1 mg PO 24 hourly Cycled every 28 days	Adverse Reactions Hematologic effects (anemia, leukopenia, neutropenia, thrombocytopenia, myelodysplastic syndrome, acute myeloid leukemia, lymphopenia); GI effects (nausea/vomiting, diarrhea, abdominal pain, dysgeusia, stomatitis, dyspepsia); CNS effects (headache, dizziness); Other effects (fatigue, decreased appetite, alopecia) Special Instructions Use with caution in patients with moderate to severe hepatic impairment Monitor CBC (baseline, monthly and as necessary), renal function tests, signs and symptoms of myeloid leukemia or myelodysplatic syndrome

Combination Therapy for Recurrent or Metastatic Breast Cancer

Monoclonal Antibody
Drug	Dosage	Remarks
Margetuximab-cmkb	In combination with chemotherapy Initial dose: 15 mg/kg 120-min IV infusion Maintenance dose: 15 mg/kg 30-minutes IV infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity	Adverse Reactions GI effects (nausea/vomiting, diarrhea, constipation, abdominal pain, decreased appetite); Musculoskeletal effects (arthralgia/myalgia, extremity pain); Respiratory effects (dyspnea, cough); Dermatologic effects (alopecia, palmar-plantar erythrodysesthesia); Other effects (fatigue/asthenia, headache, pyrexia, peripheral neuropathy, infusion-related reactions) Special Instructions Use with caution in patients with increased cardiac risk Conduct thorough cardiac assessment, including history, physical examination and determination of LVEF by echocardiogram or MUGA scan
Programmed Cell Death Protein 1 (PD-1)/Programmed Cell Death Ligand 1 (PD-L1) Inhibitor
Atezolizumab	In combination with albumin-bound Paclitaxel: 840 mg IV infusion over 1 hour every 2 weeks or 1,200 mg IV infusion over 1 hour every 3 weeks or 1,680 mg IV infusion every 4 weeks administered prior to Paclitaxel	Adverse Reactions GI effects (nausea, decreased appetite, diarrhea, constipation); Hematologic effects (anemia, thrombocytopenia, neutropenia); Other effects (fatigue, rash, alopecia, peripheral neuropathy) Special Instructions Not to be administered as IV bolus or push Use with caution in patients with severe hepatic impairment Monitor patients for immune-related adverse reactions:Pneumonitis, hepatitis, colitis or diarrhea, endocrinopathies, meningitis or encephalitis, motor and sensory neuropathy, acute pancreatitis, myocarditis, nephritis, suspected severe skinreactions Permanently discontinue in the presence of any grade 3 recurring immune-related adverse reactions or any grade 4 immune-related adverse reactions except for endocrinopathies that are controlled with replacement hormone Monitor AST, ALT, bilirubin and thyroid function before and regularly during treatment
Protein Kinase Inhibitors
Abemaciclib	In combination with Fulvestrant or an aromatase inhibitor or Tamoxifen: 150 mg PO 12 hourly Monotherapy: 200 mg PO 12 hourly	Adverse Reactions GI effects (nausea/vomiting, diarrhea, abdominal pain, decreased appetite); Hematologic effects (anemia, neutropenia, leukopenia, thrombocytopenia); Other effects (headache,infections, alopecia, fatigue) Special Instructions Use with caution in patients with new or worsening respiratory symptoms, hepatic impairment, venous thromboembolism Monitor CBC, LFTs, signs of thrombosis and pulmonary embolism
Everolimus	In combination with Exemestane: 10 mg PO 24 hourly May be reduced to 5 mg PO 24 hourly	Adverse Reactions GI effects (nausea/vomiting, diarrhea, dysgeusia); Hematologic effects (anemia, thrombocytopenia); Other effects (anorexia, hypertriglyceridemia, hyperglycemia, hypercholesterolemia, headache, pneumonitis, cough, dyspnea, rash, dry skin, decreased weight) Special Instructions Use with caution in patients with severe hepatic impairment, new or worsening respiratory symptoms, oral ulceration, carcinoid tumors Treat preexisting infection prior to treatment Monitor renal function, fasting serum glucose level, HbA1C, CBC
Inavolisib	In combination with Palbociclib and Fulvestrant: 9 mg PO 24 hourly	Adverse Reactions GI effects (stomatitis, nausea, diarrhea); Hematologic effects (decreased neutrophils, hemoglobin, platelets, lymphocytes); Metabolic effects (increased fasting glucose, creatinine, ALT, decreased calcium, potassium, sodium, magnesium); Other effects (fatigue, rash, decreased appetite, COVID-19 infection, headache) Special Instructions May be taken with or without food Test fasting glucose levels, HbA1C levels, and optimize fasting glucose prior to treatment initiation Monitor fasting glucose levels and for signs and symptoms of diarrhea and stomatitis
Palbociclib	In combination with Fulvestrant or an aromatase inhibitor: 125 mg PO 24 hourly for 21 days followed by 7 days off treatment	Adverse Reactions GI effects (nausea/vomiting, diarrhea, stomatitis, decreased appetite); Hematologic effects (anemia, neutropenia, leukopenia, thrombocytopenia); Other effects (upper respiratory tract infection, alopecia, asthenia, peripheral neuropathy and epistaxis, pulmonary embolism, fatigue) Special Instructions Monitor CBC prior to start of therapy, on day 14 of the first 2 cycles then at the beginning of each cycle Monitor for signs and symptoms of infection and pulmonary embolism
Ribociclib	In combination with Fulvestrant or an aromatase inhibitor: 600 mg PO 24 hourly for 21 consecutive days followed by 7 days off treatment (28-day cycle)	Adverse Reactions Hematologic effects (neutropenia, leukopenia); GI effects (nausea/vomiting, diarrhea, constipation, increased liver enzymes); Metabolic effects (hypophosphatemia, hypokalemia); Other effects (alopecia, headache, back pain, insomnia) Special Instructions Use with caution in patients with moderate-severe hepatic impairment, cardiac disease (eg cardiomyopathy, history of arrhythmia) Monitor serum electrolytes prior to initiation of treatment, at the beginning of the first 6 cycles, and as clinically indicated Perform LFTs and CBC before initiating therapy, and monitor every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles and as clinically indicated
Vascular Endothelial Growth Factor (VEGF) Inhibitor
Bevacizumab	In combination with Paclitaxel: 10 mg/kg IV infusion over 90 minutes every 2 weeks or 15 mg/kg IV infusion over 90 minutes every 3 weeks	Adverse Reactions Hematologic effects (leukopenia, thrombocytopenia, febrile neutropenia, anemia); Metabolic/endocrine effects (hypomagnesemia, hyponatremia); CNS effects (headache, peripheral sensory neuropathy, dysarthria, asthenia, fatigue, syncope, somnolence, cerebrovascular accident); GI effects (nausea/vomiting, intestinal perforation and obstruction, ileus, abdominal pain, stomatitis; anorexia, dysgeusia); CV effects (hypertension, CHF, supraventricular tachycardia, arterial thromboembolism, DVT, hemorrhage, pulmonary embolism); Musculoskeletal effects (arthralgia, myalgia, muscular weakness); Respiratory effects (hypoxia, epistaxis, dyspnea); Other effects (palmar-plantar erythrodysesthesia syndrome, proteinuria, UTI pain, mucosal inflammation, sepsis, abscess, infection, dehydration) Special Instructions Not to be administered as IV bolus or push Contraindicated in patients with hypersensitivity to Bevacizumab, Chinese hamster ovary cell products or recombinant human or humanized Ab Use with caution in patients with GI and gallbladder perforation, fistulae, necrotizing fasciitis, hypertension, arterial or venous thromboembolism Monitor BP during treatment, proteinuria before and during therapy and signs and symptoms of CNS bleeding

Combination Therapy Regimens

Preoperative/Adjuvant Combination Therapy Regimens for Breast Cancer

Drug	Dosage	Remarks
Cyclophosphamide + Methotrexate + 5-Fluorouracil	Cyclophosphamide: 100 mg/m² PO on days 1-14 Methotrexate: 40 mg/m² IV on days 1 and 8 5-Fluorouracil: 600 mg/m² IV on days 1 and 8 Cycled every 28 days for 6 cycles or Cyclophosphamide: 600 mg/m² PO on day 1 Methotrexate: 40 mg/m² IV on day 1 5-Fluorouracil: 600 mg/m² IV on day 1 Cycled every 21 days for 8 cycles	Adverse Reactions Carboplatin CNS effect (neurotoxicity); Endocrine effects (hyponatremia, hypomagnesemia, hypocalcemia, hypokalemia); GI effects (nausea/vomiting, abdominal pain); Hematologic effects (leukopenia, anemia, neutropenia, thrombocytopenia); Hepatic effect (increased liver enzymes); Neuromuscular effect (weakness); Other effects (nephrotoxicity, allergy, pain, loss of vision with high dose) Cyclophosphamide GI effects (nausea/vomiting, anorexia, mucositis); CNS effect (headache); GU effect (acute hemorrhagic cystitis or urinary fibrosis); Dermatologic effects (alopecia, rash); Hematologic effect (leukopenia); Respiratory effects (rhinorrhea, nasal congestion); Other effects (fertility impairment, renal tubular necrosis, SIADH may occur with doses >50 mg/kg) Docetaxel Ophthalmologic effect (epiphora with canalicular stenosis); CNS effects (paresthesia, dysesthesia); Dermatologic effects (alopecia, rash, erythema, desquamation, anaphylaxis); GI effects (nausea/vomiting, stomatitis, diarrhea); CV effects (hypotension, edema); Hematologic effects (neutropenia, leukopenia, anemia, thrombocytopenia); Other effects (weakness, bronchospasm, increased transaminases, pain) Doxorubicin Dermatologic effects (injection site reaction, alopecia, urticaria, rash); GI effects (nausea/vomiting, stomatitis, GI ulceration, diarrhea, loss of appetite); GU effects (urinary frequency, hematuria); Hematologic effects (leukopenia, anemia, thrombocytopenia); CV effects (transient ECG abnormalities, CHF); Other effects (discoloration of body fluids, hyperuricemia, infertility) Epirubicin CNS effect (changes in sensorium); Dermatologic effects (injection site reaction, alopecia, anaphylaxis, rash); GI effects (nausea/vomiting, diarrhea, loss of appetite); Hematologic effects (leukopenia, anemia, thrombocytopenia); Other effects (fever, menstrual dysfunction, hot flushes) Fluorouracil CV effects (myocardial ischemia, angina); CNS effects (confusion, headache, acute cerebellar syndrome); Dermatologic effects (alopecia, rash, vein pigmentation, palmar-plantar erythrodysesthesia syndrome, anaphylaxis); GI effects (bleeding, esophagopharyngitis, nausea/vomiting, ulceration); Hematologic effects (leukopenia, anemia, thrombocytopenia); Ophthalmologic effects (photophobia, visual disturbances, lacrimation, nystagmus); Other effect (nose bleeding) Methotrexate GI effects (stomatitis, gingivitis, nausea/vomiting, diarrhea, loss of appetite, intestinal perforation); CNS effect (dizziness); Dermatologic effects (alopecia, rash, severe reactions eg Stevens-Johnson syndrome, toxic epidermal necrolysis); Hematologic effects (leukopenia, thrombocytopenia); Other effects (hyperuricemia, menstrual dysfunction, fever, chills) Paclitaxel (Albumin-bound) CV effects (ECG abnormality, edema, hypotension); GI effects (nausea/vomiting); Hematologic effects (neutropenia, anemia); Hepatic effect (elevated liver enzymes); Other effects (candidiasis infection, vision disturbances, sensory neuropathy) Paclitaxel (Conventional) Dermatologic effects (rash, alopecia, injection site reaction, hypersensitivity reaction); CV effects (edema, flushing, bradycardia); GI effects (nausea/vomiting, stomatitis, mucositis, diarrhea); Hematologic effects (neutropenia, leukopenia); Hepatic effect (elevated liver enzymes); Other effect (peripheral neuropathy) Pembrolizumab GI effects (nausea, constipation, decreased appetite, diarrhea); Respiratory effects (cough, pneumonitis, dyspnea, pneumonia); Dermatologic effects (pruritus, rash, cellulitis); Other effects (fatigue, arthralgia, renal failure, pain) Pertuzumab GI effects (diarrhea, decreased appetite, mucositis, nausea/vomiting, stomatitis); Dermatologic effects (rash, pruritus); Hematologic effects (neutropenia, anemia); Other effects (fatigue, headache, fever, upper respiratory tract infection) Effects with combination therapy: Heart failure, dyspnea, decreased LVEF, pleural effusion, sepsis Trastuzumab CNS effects (headache, dizziness, insomnia, peripheral neuritis); Dermatologic effects (acne, rash, severe hypersensitivity reaction eg anaphylaxis); GI effects (abdominal pain, anorexia, diarrhea, nausea/vomiting); CV effects (edema, palpitation, hypotension, heart failure); Hematologic effects (leukopenia, anemia); Other effects (infusion-related symptoms [eg fever, chills]; rash, weakness, back pain, dyspnea, cough) Special Instructions Carboplatin Taxane derivatives should be given before platinum-based agents Use with caution in patients with renal impairment Cyclophosphamide Use with caution in patients with hepatic or renal impairment Docetaxel Premedication with corticosteroids, Diphenhydramine and H₂ antagonist is required for all patients Contraindicated in patients with preexisting bone marrow suppression with neutrophil count of <1,500 cells/mm³, and patients with hepatic impairment Doxorubicin Avoid in patients with preexisting bone marrow suppression and CHF Use with caution in patients with previous radiation therapy Baseline cardiac evaluation (ECG, LVEF) is advised especially in patients at high risk of cardiac toxicity May cause secondary leukemia Epirubicin Avoid in patients with cardiac disease (severe myocardial insufficiency, severe arrhythmias and recent MI) and in patients with baseline neutrophil count 1,500 cells/mm³ Use with caution in patients with preexisting cardiac disease, hepatic and renal dysfunction and in patients who have previously received anthracyclines May cause secondary leukemia Fluorouracil Contraindicated in patients with dihydropyrimidinedehydrogenase (DPD) enzyme deficiency Use with caution in patients with hepatic or renal impairment, patients with high-dose pelvic radiation or previous exposure to alkylating agents Methotrexate Use with caution in patients with preexisting bone marrow suppression, renal or hepatic impairment, peptic ulcer disease and ulcerative colitis Paclitaxel (Albumin-bound) Premedication with corticosteroids, Diphenhydramine and H₂ antagonist is required for all patients Contraindicated in patients with baseline neutrophil count of <1,500 cells/mm³ Use with caution in patients with renal or hepatic dysfunction Pembrolizumab Withhold treatment if any of the following occurs: Moderate pneumonitis, moderate or severe immune-mediated colitis, moderate hypophysitis, severe hyperglycemia, moderate immune-mediated nephritis Discontinue if life-threatening adverse events of pneumonitis, colitis, hypophysitis, hyperthyroidism, nephritis, infusion reactions, severe liver enzyme elevations occur Monitor liver enzymes, serum creatinine, and thyroid and renal function Pertuzumab Assess LVEF at baseline and during therapy because of risk of heart failure Contraindicated in patients with hypersensitivity to Pertuzumab Trastuzumab Use with caution in patients with preexisting cardiac disease, previous exposure to radiation therapy or anthracyclines Monitor cardiac function at baseline, during and after treatment
Docetaxel + Carboplatin	Docetaxel: 75 mg/m² IV on day 1 Carboplatin: AUC 6 IV on day 1 Cycled every 21 days for 4-6 cycles
Docetaxel + Carboplatin + Trastuzumab	Docetaxel: 75 mg/m² IV on day 1 Carboplatin: AUC 6 IV on day 1 Cycled every 21 days for 6 cycles* With Trastuzumab: 4 mg/kg IV on week 1 Followed by: Trastuzumab: 2 mg/kg IV x 17 weeks Followed by: Trastuzumab: 6 mg/kg IV Cycled every 21 days to complete 1 year of therapy or Trastuzumab: 8 mg/kg IV on week 1 Followed by: Trastuzumab: 6 mg/kg IV every 21 days to complete 1 year of therapy
Docetaxel + Carboplatin + Trastuzumab + Pertuzumab	Docetaxel: 75 mg/m² IV on day 1 Carboplatin: AUC 6 IV on day 1 Cycled every 21 days for 6 cycles* With Trastuzumab: 8 mg/kg IV on day 1 Pertuzumab: 840 mg IV on day 1 Followed by: Trastuzumab: 6 mg/kg IV on day 1 Pertuzumab: 420 mg IV on day 1 Cycled every 21 days to complete 1 year of therapy
Docetaxel + Cyclophosphamide	Docetaxel: 75 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4-6 cycles
Docetaxel + Cyclophosphamide + Trastuzumab	Docetaxel: 75 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles* With Trastuzumab: 4 mg/kg IV on week 1 Followed by: Trastuzumab: 2 mg/kg IV weekly x 11 weeks Followed by: Trastuzumab: 6 mg/kg IV Cycled every 21 days to complete 1 year of therapy or Trastuzumab: 8 mg/kg IV on week 1 Followed by: Trastuzumab: 6 mg/kg IV every 21 days to complete 1 year of therapy
Docetaxel + Doxorubicin + Cyclophosphamide(TAC)	Docetaxel: 75 mg/m² IV on day 1 Doxorubicin: 50 mg/m² IV on day 1 Cyclophosphamide: 500 mg/m² IV on day 1 Cycled every 21 days for 6 cycles*
Dose-dense Doxorubicin + Cyclophosphamide	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles or every 14 days for 4 cycles for dose-dense regimen
Dose-dense Doxorubicin + Cyclophosphamide + Paclitaxel	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 14 days for 4 cycles* Followed by: Paclitaxel: 175 mg/m² IV infusion over 3 hours on day 1 Cycled every 14 days for 4 cycles*
Dose-dense Doxorubicin + Cyclophosphamide + Paclitaxel	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 14 days for 4 cycles* Followed by: Paclitaxel: 80 mg/m² IV infusion for 1 hour weekly x 12 weeks
Dose-dense Doxorubicin + Cyclophosphamide + Paclitaxel + Trastuzumab	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 14 days for 4 cycles Followed by: Paclitaxel: 175 mg/m² IV infusion for 3 hours on day 1 Cycled every 14 days for 4 cycles With Trastuzumab: 4 mg/kg IV with 1st dose of Paclitaxel Followed by: Trastuzumab: 2 mg/kg IV weekly to complete 1 year *Alternative:* Trastuzumab 6 mg/kg IV every3 weeks following completion of Paclitaxel, and given to complete 1 year of Trastuzumab treatment
Doxorubicin + Cyclophosphamide	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles
Doxorubicin + Cyclophosphamide + Docetaxel	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles* Followed by: Docetaxel: 100 mg/m² IV on day 1 Cycled every 21 days for 4 cycles*
Doxorubicin + Cyclophosphamide + Paclitaxel	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles Followed by: Paclitaxel: 80 mg/m² IV infusion for 1 hour weekly x 12 weeks
Doxorubicin + Cyclophosphamide + Docetaxel + Trastuzumab	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles Followed by: Docetaxel: 75-100 mg/m² IV on day 1 Cycled every 21 days for 4 cycles With Trastuzumab: 4 mg/kg IV on week 1 Followed by: Trastuzumab: 2 mg/kg IV weekly x 11 weeks Followed by: Trastuzumab: 6 mg/kg IV Cycled every 21 days to complete 1 year of Trastuzumab therapy
Doxorubicin + Cyclophosphamide + Paclitaxel + Trastuzumab	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles Followed by: Paclitaxel: 80 mg/m² IV infusion over 1 hour weekly for 12 weeks With Trastuzumab: 4 mg/kg IV with first dose of Paclitaxel Followed by: Trastuzumab: 2 mg/kg IV weekly to complete 1 year *Alternative:* Trastuzumab 6 mg/kg IV every 3 weeks following completion of Paclitaxel and given to complete 1 year of Trastuzumab treatment
Doxorubicin + Cyclophosphamide + Docetaxel + Trastuzumab	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles Followed by: Docetaxel: 75-100 mg/m² IV on day 1 Cycled every 21 days for 4 cycles With Trastuzumab: 4 mg/kg IV on week 1 *Followed by:* Trastuzumab: 2 mg/kg IV weekly x 11 weeks Followed by: Trastuzumab: 6 mg/kg IV Cycled every 21 days to complete 1 year of Trastuzumab therapy
Doxorubicin + Cyclophosphamide + Paclitaxel +Trastuzumab	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles Followed by: Paclitaxel: 80 mg/m² IV infusion over 1 hour weekly for 12 weeks With Trastuzumab: 4 mg/kg IV with 1st dose of Paclitaxel Followed by: Trastuzumab: 2 mg/kg IV weekly to complete 1 year *Alternative:* Trastuzumab 6 mg/kg IV every 3 weeks following completion of Paclitaxel and given to complete 1 year of Trastuzumab treatment
Doxorubicin + Cyclophosphamide + Pertuzumab +Trastuzumab +Paclitaxel	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles Followed by: Pertuzumab: 840 mg/m² IV on day 1 followed by 420 mg IV Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV Paclitaxel: 80 mg/m² IV on days 1, 8, and 15 Cycled every 21 days for 4 cycles Followed by: Trastuzumab: 6 mg/kg IV on day 1 Pertuzumab: 420 mg/m² IV on day 1 Cycled every 21 days for 4 cycles
Doxorubicin + Cyclophosphamide + Pertuzumab +Trastuzumab + Docetaxel + Trastuzumab + Pertuzumab	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles Followed by: Pertuzumab: 840 mg/m² IV on day 1 followed by 420 mg IV Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV Docetaxel: 75-100 mg/m² IV on day 1 Cycled every 21 days for 4 cycles Followed by: Trastuzumab: 6 mg/kg IV Pertuzumab: 420 mg/m² IV on day 1 Cycled every 21 days to complete 1 year of therapy
Epirubicin + Cyclophosphamide	Epirubicin: 100 mg/m² IV on day 1 Cyclophosphamide: 830 mg/m² IV on day 1 Cycled every 21 days for 8 cycles
Paclitaxel + Carboplatin	Paclitaxel: 80 mg/m² IV on days 1, 8 and 15 Carboplatin: AUC 5 or 6 IV on day 1 Cycled every 21 days for 4 cycles or Paclitaxel: 80 mg/m² IV on days 1, 8 and 15 Carboplatin: AUC 1.5-2 IV on days 1, 8 and 15 Cycled every 28 days for 6 cycles
Paclitaxel + Carboplatin + Trastuzumab + Pertuzumab	Paclitaxel: 80 mg/m² IV on days 1 and 8 Carboplatin: AUC 6 IV on day 1 Cycled every 21 days for 9 cycles Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV Pertuzumab: 840 mg IV on day 1 followed by 420 mg IV Cycled every 21 days to complete 1 year of therapy
Paclitaxel +Trastuzumab	Paclitaxel: 80 mg/m² IV weekly x 12 weeks Trastuzumab: 4 mg/kg IV with first dose of Paclitaxel Followed by: Trastuzumab: 2 mg/kg IV weekly to complete 1 year *Alternative:* Trastuzumab 6 mg/kg IV every 3 weeks following completion of Paclitaxel, and given to complete 1 year of Trastuzumab treatment
Paclitaxel +Trastuzumab + Pertuzumab	Paclitaxel: 80 mg/m² IV on day 1 weekly x 12 weeks Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV Pertuzumab: 840 mg IV on day 1 followed by 420 mg IV Cycled every 21 days for 4 cycles Followed by: Trastuzumab: 6 mg/kg IV Pertuzumab: 420 mg/m² IV on day 1 Cycled every 21 days to complete 1 year of therapy
Pembrolizumab +Doxorubicin + Cyclophosphamide	Pembrolizumab: 200 mg IV on day 1 Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles
Pembrolizumab + Epirubicin + Cyclophosphamide	Pembrolizumab: 200 mg IV on day 1 Epirubicin: 90 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days for 4 cycles followed by Pembrolizumab: 200 mg IV on day 1 Cycled every 21 days for 9 cycles
Pembrolizumab + Paclitaxel +Carboplatin	Pembrolizumab: 200 mg IV on day 1 Paclitaxel: 80 mg/m² IV on days 1, 8 and 15 Carboplatin: AUC 5 IV on day 1 or AUC1.5 IV on days 1, 8, and 15 Cycled every 21 days for 4 cycles
Pertuzumab + Trastuzumab	Loading dose: 1,200 mg Pertuzumab/600 mg Trastuzumab SC x 8 minutes with 30 minutes observation time after administration Maintenance dose: 600 mg Pertuzumab/600 mg Trastuzumab SC x 5 minutes every 3 weeks with 15 minutes observation time after administration

*All cycles are with myeloid growth factor support. Specific prescribing information on Filgrastim and Pegfilgrastim may be found in the latest MIMS.

Combination Therapy for Recurrent or Metastatic Breast Cancer

Drug	Dosage	Remarks
Alpelisib + Fulvestrant	Alpelisib: 300 mg PO 24 hourly on days 1-28 Fulvestrant: 500 mg IM 24 hourly on days 1 and 15 Cycled for 28 days x 1 cycle followed by Alpelisib: 300 mg PO 24 hourly on days 1-28 Fulvestrant: 500 mg IM 24 hourly on day 1 Cycled every 28 days until disease progression or unacceptable toxicity	Adverse Reactions Alpelisib GI effects (nausea/vomiting, diarrhea, stomatitis); Metabolic effects (hyperglycemia, increased creatinine); Hepatic effects (increased lipase, increased ALT, increased GGT); Hematologic effects (lymphocytopenia, prolonged aPTT, decreased hemoglobin count); Other effects (rash, decreased appetite, alopecia, fatigue, UTI) Bevacizumab GI effects (GI perforation, diarrhea, abdominal pain); Respiratory effects (pulmonary hemorrhage/hemoptysis); CV effects (hypertension, arterial thromboembolism); Other effects (fatigue, asthenia) Capecitabine GI effects (diarrhea, nausea/vomiting, abdominal pain, stomatitis, constipation, dyspepsia, flatulence); Hematologic effects (neutropenia, anemia, lymphopenia); CNS effects (anorexia, insomnia, depression, headache, dizziness); Respiratory effects (nasopharyngitis, lower respiratory tract infection, rhinorrhea, cough, dyspnea); CV effect (edema); Other effects (fatigue, hand-foot syndrome, increased blood bilirubin) Capivasertib Hematologic effects (decreased hemoglobin, lymphocytes, leukocytes and/or neutrophils); Metabolic effects (increased fasting glucose, random glucose, triglycerides and/or creatinine); GI effects (nausea/vomiting, stomatitis, diarrhea); Other effect (fatigue) Carboplatin CNS effect (neurotoxicity); Endocrine effects (hyponatremia, hypomagnesemia, hypocalcemia, hypokalemia); GI effects (nausea/vomiting, abdominal pain); Hematologic effects (leukopenia, anemia, neutropenia, thrombocytopenia); Hepatic effect (increased liver enzymes); Neuromuscular effect (weakness); Other effects (nephrotoxicity, allergy, pain, loss of vision with high dose) Cyclophosphamide GI effects (nausea/vomiting, anorexia, mucositis); CNS effect (headache); GU effect (acute hemorrhagic cystitis or urinary fibrosis); Dermatologic effects (alopecia, rash); Hematologic effect (leukopenia); Respiratory effects (rhinorrhea, nasal congestion); Other effects (fertility impairment, renal tubular necrosis, SIADH may occur with doses >50 mg/kg) Docetaxel Ophthalmologic effect (epiphora with canalicular stenosis); CNS effects (paresthesia, dysesthesia); Dermatologic effects (alopecia, rash, erythema, desquamation, anaphylaxis); GI effects (nausea/vomiting, stomatitis, diarrhea); CV effects (hypotension, edema); Hematologic effects (neutropenia, leukopenia, anemia, thrombocytopenia); Other effects (weakness, bronchospasm, increased transaminases, pain) Doxorubicin Dermatologic effects (injection site reaction, alopecia, urticaria, rash); GI effects (nausea/vomiting, stomatitis, GI ulceration, diarrhea, loss of appetite); GU effects (urinary frequency, hematuria); Hematologic effects (leukopenia, anemia, thrombocytopenia); CV effects (transient ECG abnormalities, CHF); Other effects (discoloration of body fluids, hyperuricemia, infertility) Epirubicin CNS effect (changes in sensorium); Dermatologic effects (injection site reaction, alopecia, anaphylaxis, rash); GI effects (nausea/vomiting, diarrhea, loss of appetite); Hematologic effects (leukopenia, anemia, thrombocytopenia); Other effects (fever, menstrual dysfunction, hot flushes) Eribulin Hematologic effects (neutropenia, leukopenia, anemia); CNS effects (peripheral neuropathy, headache); GI effects (nausea/vomiting, constipation, diarrhea); Musculoskeletal effects (arthralgia, back pain, myalgia, pain in extremity); Other effects (asthenia, fatigue, pyrexia, decreased weight, alopecia, cough, dyspnea) Fluorouracil CV effects (myocardial ischemia, angina); CNS effects (confusion, headache, acute cerebellar syndrome); Dermatologic effects (alopecia, rash, vein pigmentation, palmar-plantar erythrodysesthesia syndrome, anaphylaxis); GI effects (bleeding, esophagopharyngitis, nausea/vomiting, ulceration); Hematologic effects (leukopenia, anemia, thrombocytopenia); Ophthalmologic effects (photophobia, visual disturbances, lacrimation, nystagmus); Other effect (nose bleeding) Fulvestrant Local injection site reactions, asthenia, nausea, elevated hepatic enzymes Gemcitabine CV effect (edema); GI effects (diarrhea, paralytic ileus, nausea/vomiting); Dermatologic effects (rash, alopecia, pruritus); Hepatic effects (elevated liver enzymes and total bilirubin level); Other effects (bone marrow suppression, hemolytic uremic syndrome, pain, fever) Inavolisib GI effects (stomatitis, nausea, diarrhea); Hematologic effects (decreased neutrophils, hemoglobin, platelets, lymphocytes); Metabolic effects (increased fasting glucose, creatinine, ALT, decreased calcium, potassium, sodium, magnesium); Other effects (fatigue, rash, decreased appetite, COVID-19 infection, headache) Lapatinib GI effects (nausea/vomiting, diarrhea, abdominal pain, stomatitis, dyspepsia); Dermatologic effects (rash, palmar-plantar erythrodysesthesia); Hepatic effects (elevated liver enzymes and total bilirubin level); Other effects (dyspnea, anemia, fatigue, back pain) Letrozole GI effects (nausea/vomiting, changes in weight, abdominal pain, bowel movement changes); CNS effects (fatigue, headache, dizziness, depression); CV effects (hypertension, edema); Dermatologic effects (alopecia, rash, pruritus); Other effects (cough, dyspnea, infection, decreased bone mineral density, weakness, hot flashes, hypercholesterolemia) Margetuximab-cmkb GI effects (nausea/vomiting, diarrhea, constipation, abdominal pain, decreased appetite); Musculoskeletal effects (arthralgia/myalgia, extremity pain); Respiratory effects (dyspnea, cough); Dermatologic effects (alopecia, palmar-plantar erythrodysesthesia); Other effects (fatigue/asthenia, headache, pyrexia, peripheral neuropathy, infusion-related reactions) Methotrexate GI effects (stomatitis, gingivitis, nausea/vomiting, diarrhea, loss of appetite, intestinal perforation); CNS effect (dizziness); Dermatologic effects (alopecia, rash, severe reactions eg Stevens-Johnson syndrome, toxic epidermal necrolysis); Hematologic effects (leukopenia, thrombocytopenia); Other effects (hyperuricemia, menstrual dysfunction, fever, chills) Neratinib GI effects (nausea/vomiting, diarrhea, abdominal pain, stomatitis, dyspepsia, abdominal distention, decreased appetite); Dermatologic effects (nail disorder, dry skin); Other effects (fatigue, rash, decreased weight, muscle spasms, increased AST/ALT, urinary tract infection) Paclitaxel (Albumin-bound) CV effects (ECG abnormality, edema, hypotension); GI effects (nausea/vomiting); Hematologic effects (neutropenia, anemia); Hepatic effect (elevated liver enzymes); Other effects (candidiasis infection, vision disturbances, sensory neuropathy) Paclitaxel (Conventional) Dermatologic effects (rash, alopecia, injection site reaction, hypersensitivity reaction); CV effects (edema, flushing, bradycardia); GI effects (nausea/vomiting, stomatitis, mucositis, diarrhea); Hematologic effects (neutropenia, leukopenia); Hepatic effect (elevated liver enzymes); Other effect (peripheral neuropathy) Palbociclib GI effects (nausea/vomiting, diarrhea, stomatitis, decreased appetite); Hematologic effects (anemia, neutropenia, leukopenia, thrombocytopenia); Other effects (upper respiratory tract infection, alopecia, asthenia, peripheral neuropathy and epistaxis, pulmonary embolism, fatigue) Pembrolizumab GI effects (nausea, constipation, decreased appetite, diarrhea); Respiratory effects (cough, pneumonitis, dyspnea, pneumonia); Dermatologic effects (pruritus, rash, cellulitis); Other effects (fatigue, arthralgia, renal failure, pain) Pertuzumab GI effects (diarrhea, decreased appetite, mucositis, nausea/vomiting, stomatitis); Dermatologic effects (rash, pruritus); Hematologic effects (neutropenia, anemia); Other effects (fatigue, headache, fever, upper respiratory tract infection) Effects with combination therapy: Heart failure, dyspnea, decreased LVEF, pleural effusion, sepsis Trastuzumab CNS effects (headache, dizziness, insomnia, peripheral neuritis); Dermatologic effects (acne, rash, severe hypersensitivity reaction eg anaphylaxis); GI effects (abdominal pain, anorexia, diarrhea, nausea/vomiting); CV effects (edema, palpitation, hypotension, heart failure); Hematologic effects (leukopenia, anemia); Other effects (infusion-related symptoms [eg fever, chills]; rash, weakness, back pain, dyspnea, cough) Tucatinib GI effects (nausea/vomiting, diarrhea, abdominal pain, stomatitis, decreased appetite); Hematologic effect (anemia); Dermatologic effects (palmar-plantar erythrodysesthesia, rash); Other effects (hepatotoxicity, fatigue, headache) Vinorelbine CNS effect (fatigue); GI effects (constipation, paralytic ileus, nausea/vomiting); Hematologic effects (bone marrow suppression, severe granulocytopenia, leukopenia); Hepatic effects (elevated AST and total bilirubin level); Other effects (alopecia, injection site reaction, weakness) Special Instructions Alpelisib To be taken with food Use with caution in patients with DM, new or worsening respiratory symptoms, renal impairment, history of Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis Monitor renal function, fasting serum glucose level, CBC Bevacizumab Discontinue in patients who develop GI perforation, grade 3 or 4 bleeding, arterial thromboembolic events (including CVA, TIA, MI), uncontrolled hypertension Should not be used in patients with recent pulmonary hemorrhage/hemoptysis Monitor BP; preexisting hypertension should be adequately controlled prior to initiating therapy with Bevacizumab Capecitabine Contraindicated in patients with severe renal/hepatic impairment, dihydropyrimidine dehydrogenase deficiency, severe leukopenia, neutropenia or thrombocytopenia Use with caution in patients with renal impairment, mild-moderate hepatic dysfunction, galactose intolerance, patients taking oral coumarin-derivative anticoagulants Monitor ALT, AST, serum electrolytes Capivasertib Contraindicated in patients with severe hypersensitivity to Capivasertib Use with caution in patients with moderate hepatic impairment Assess blood glucose levels before initiation and at regular intervals during treatment Monitor for signs and symptoms of cutaneous adverse reactions Carboplatin Taxane derivatives should be given before platinum-based agents Use with caution in patients with renal impairment Cyclophosphamide Use with caution in patients with hepatic or renal impairment Docetaxel Premedication with corticosteroids, Diphenhydramine and H₂ antagonist is required for all patients Contraindicated in patients with preexisting bone marrow suppression with neutrophil count of <1,500 cells/mm³, and patients with hepatic impairment Doxorubicin Avoid in patients with preexisting bone marrow suppression and CHF Use with caution in patients with previous radiation therapy Baseline cardiac evaluation (ECG, LVEF) is advised especially in patients at high risk of cardiac toxicity May cause secondary leukemia Epirubicin Avoid in patients with cardiac disease (severe myocardial insufficiency, severe arrhythmias and recent MI) and in patients with baseline neutrophil count 1,500 cells/mm³ Use with caution in patients with preexisting cardiac disease, hepatic and renal dysfunction and in patients who have previously received anthracyclines May cause secondary leukemia Eribulin Use with caution in patients with myelosuppression Correct hypokalemia, hypocalcemia and hypomagnesemia prior to treatment Fluorouracil Contraindicated in patients with dihydropyrimidinedehydrogenase (DPD) enzyme deficiency Use with caution in patients with hepatic or renal impairment, patients with high-dose pelvic radiation or previous exposure to alkylating agents Fulvestrant Avoid in patients with severe hepatic impairment Use with caution in patients with mild to moderate hepatic impairment, severe renal impairment, bleeding diatheses, thrombocytopenia, on anticoagulants, potential risk of osteoporosis; thrombolic events in patients with advanced breast cancer Gemcitabine Use with caution in patients with hepatic metastasis, hepatic or renal impairment, with concurrent radiation therapy Inavolisib May be taken with or without food Test fasting glucose levels, HbA1C levels, and optimize fasting glucose prior to treatment initiation Monitor fasting glucose levels and for signs and symptoms of diarrhea and stomatitis Lapatinib Use with caution in patients with hepatic dysfunction, with history of or predisposed to left ventricular dysfunction Letrozole Take doses with breakfast and dinner If medication is missed for ≥3 days, restart at lowest dose and increase to current dose Treatment should be maintained at maximum tolerated dose Maintain adequate hydration Avoid in patients with severe renal or hepatic impairment Use with caution in patients with supraventricular cardiac conduction abnormalities, patients with seizures, COPD, asthma, risk of GI bleeding or in patients with bladder outlet obstruction, mild-moderate liver or renal dysfunction No dosage adjustment is needed in the elderly Margetuximab-cmkb Use with caution in patients with increased cardiac risk Conduct thorough cardiac assessment, including history, physical examination and determination of LVEF by echocardiogram or MUGA scan Methotrexate Use with caution in patients with preexisting bone marrow suppression, renal or hepatic impairment, peptic ulcer disease and ulcerative colitis Paclitaxel (Albumin-bound) Premedication with corticosteroids, Diphenhydramine and H₂ antagonist is required for all patients Contraindicated in patients with baseline neutrophil count of <1,500 cells/mm³ Use with caution in patients with renal or hepatic dysfunction Paclitaxel (Conventional) Premedication with corticosteroids, Diphenhydramine and H2 antagonist is required for all patients Use with caution in patients with hepatic dysfunction Palbociclib Monitor CBC prior to start of therapy, on day 14 of the first 2 cycles then at the beginning of each cycle Monitor for signs and symptoms of infection and pulmonary embolism Pembrolizumab Withhold treatment if any of the following occurs: Moderate pneumonitis, moderate or severe immune-mediated colitis, moderate hypophysitis, severe hyperglycemia, moderate immune-mediated nephritis Discontinue if life-threatening adverse events of pneumonitis, colitis, hypophysitis, hyperthyroidism, nephritis, infusion reactions, severe liver enzyme elevations occur Monitor liver enzymes, serum creatinine, and thyroid and renal function Pertuzumab Assess LVEF at baseline and during therapy because of risk of heart failure Contraindicated in patients with hypersensitivity to Pertuzumab Trastuzumab Use with caution in patients with preexisting cardiac disease, previous exposure to radiation therapy or anthracyclines Monitor cardiac function at baseline, during and after treatment Tucatinib Use with caution in patients with new or worsening respiratory symptoms, hepatic impairment, venous thromboembolism Monitor ALT, AST and bilirubin prior to initiation, every 3 weeks and as clinically indicated Vinorelbine Use with caution in patients with ulcerated skin or cachexia Only used for IV infusion
Capecitabine + Lapatinib	Capecitabine: 1,000 mg/m² PO 12 hourly on days 1-14 Lapatinib: 1,250 mg PO 24 hourly on days 1-21 Cycled every 21 days
Capivasertib + Fulvestrant	Capivasertib: 400 mg PO 12 hourly on days 1-4, 8-11, 15-28 and 22-25 Fulvestrant: 500 mg IM 24 hourly on days 1 and 15 Cycled for 28 days x 1 cycle followed by Capivasertib: 400 mg PO 12 hourly on days 1-4, 8-11, 15-28 and 22-25 Fulvestrant: 500 mg IM 24 hourly on day 1 starting with cycle 2 Cycled every 28 days until disease progression or unacceptable toxicity
Carboplatin + albumin-bound Paclitaxel	Carboplatin: AUC 2 IV 24 hourly on days 1 and 8 Albumin-bound Paclitaxel: 125 mg/m² IV infusion24 hourly on days 1 and 8 Cycled every 21 days
Carboplatin + Paclitaxel	Paclitaxel: 175-200 mg/m² IV 24 hourly on day 1 Carboplatin: AUC 6 IV 24 hourly on day 1 Cycled every 21 days or Paclitaxel: 100 mg/m² IV 24 hourly on days 1, 8 and 15 Carboplatin: AUC 2 IV 24 hourly on days 1, 8 and 15 Cycled every 28 days
Cyclophosphamide + Methotrexate + 5-Fluorouracil	Cyclophosphamide: 100 mg/m² PO on days 1-14 Methotrexate: 40 mg/m² IV on days 1 and 8 5-Fluorouracil: 600 mg/m² IV on days 1 and 8 Cycled every 28 days
Docetaxel + Capecitabine	Docetaxel: 75 mg/m² IV on day 1 Capecitabine: 950 mg/m² PO 12 hourly on days 1-14 Cycled every 21 days
Doxorubicin + Cyclophosphamide	Doxorubicin: 60 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 Cycled every 21 days
Doxorubicin + Paclitaxel	Doxorubicin: 50 mg/m² IV on day 1 Paclitaxel: 220 mg/m² IV infusion over 3 hours administered 24 hours after Doxorubicin Cycled every 21 days
Epirubicin + Cyclophosphamide	Epirubicin: 75 mg/m² IV on day 1 Cyclophosphamide: 600 mg/m² IV on day 1 or Epirubicin: 100 mg/m² IV on day 1 Cyclophosphamide: 830 mg/m² IV on day 1 Cycled every 21 days
Gemcitabine + Carboplatin	Gemcitabine: 1,000 mg/m² IV on days 1 and 8 Carboplatin: AUC 2 IV on days 1 and 8 Cycled every 21 days
Gemcitabine + Paclitaxel	Gemcitabine: 1,250 mg/m² IV on days 1 and 8 (following Paclitaxel on day 1) Paclitaxel: 175 mg/m² IV infusion over 3 hours on day 1 Cycled every 21 days
Inavolisib + Palbociclib + Fulvestrant	Inavolisib: 9 mg PO on days 1-28 Palbociclib: 125 mg PO on days 1-21 Fulvestrant: 500 mg IM on days 1 and 15 Cycled for 28 days followed by Inavolisib: 9 mg PO on days 1-28 Palbociclib: 125 mg PO on days 1-21 Fulvestrant: 500 mg IM on day 1 Cycled every 28 days
Lapatinib + Trastuzumab	Lapatinib: 1,000 mg PO 24 hourly continuously Trastuzumab: 4 mg/kg IV (loading dose) on day 1 followed by 2 mg/kg IV weekly or Trastuzumab: 8 mg/kg IV (loading dose) on day 1 followed by 6 mg/kg IV every 21 days
Margetuximab-cmkb + Capecitabine	Margetuximab-cmkb: 15 mg/kg IV on day 1 Capecitabine: 1,000 mg/m² PO 12 hourly on days 1-14 Cycled every 21 days
Margetuximab-cmkb + Eribulin	Margetuximab-cmkb: 15 mg/kg IV on day 1 Eribulin: 1.4 mg/m² IV on days 1 and 8 Cycled every 21 days
Margetuximab-cmkb + Gemcitabine	Margetuximab-cmkb: 15 mg/kg IV on day 1 Gemcitabine: 1,000 mg/m² IV on days 1 and 8 Cycled every 21 days
Margetuximab-cmkb + Vinorelbine	Margetuximab-cmkb: 15 mg/kg IV on day 1 Vinorelbine: 25-30 mg/m² IV on days 1 and 8 Cycled every 21 days
Neratinib + Capecitabine	Neratinib: 240 mg PO 24 hrly on days 1-21 Capecitabine: 750 mg/m² PO 12 hourly on days 1-14 Cycled every 21 days or Neratinib: 120 mg PO 24 hourly on days 1-7 followed by 160 mg PO 24 hourly on days 8-14 followed by 240 mg PO 24 hourly on days 15-21 Capecitabine: 750 mg/m² PO 12 hourly on days 1-14 Cycled every 21 days x 1 cycle followed by Neratinib: 240 mg PO 24 hourly on days 1-21 Capecitabine: 750 mg/m² PO 12 hourly on days 1-14 Cycled every 21 days beginning with cycle 2
Paclitaxel + Carboplatin + Trastuzumab	Paclitaxel: 80 mg/m² IV infusion over 1 hour on days 1, 8 and 15 Carboplatin: AUC 2 IV on days 1, 8 and 15 Cycled every 28 days Trastuzumab: 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV every 21 days or Carboplatin: AUC 6 IV on day 1 Paclitaxel: 175 mg/m² IV infusion on day 1 Cycled every 21 days Trastuzumab: 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV every 21 days
Pembrolizumab + albumin-bound Paclitaxel	Pembrolizumab: 200 mg IV on day 1 every 21 days Albumin-bound Paclitaxel: 100 mg/m² IV infusion over 1 hour on days 1, 8 and 15 every 28 days Cycled every 21 days
Pembrolizumab + Paclitaxel	Pembrolizumab: 200 mg IV on day 1 every 21 days Paclitaxel: 90 mg/m² IV infusion over 1 hour on days 1, 8 and 15 every 28 days Cycled every 28 days
Pembrolizumab + Gemcitabine + Carboplatin	Pembrolizumab: 200 mg IV on day 1 Gemcitabine: 1,000 mg/m² IV on days 1 and 8 Carboplatin: AUC 2 IV on days 1 and 8 Cycled every 21 days
Pertuzumab + Trastuzumab + Docetaxel	Pertuzumab: 840 mg IV on day 1 followed by 420 mg IV Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV Docetaxel: 75-100 mg/m² IV on day 1 Cycled every 21 days or Loading dose: 1,200 mg Pertuzumab/600 mg Trastuzumab SC x 8 minutes with 30 minutes observation time after administration Maintenance dose: 600 mg Pertuzumab/600 mg Trastuzumab SC x 5 minutes every 3 weeks with 15 minutes observation time after administration Docetaxel: 75-100 mg/m² IV on day 1 every 3 weeks
Pertuzumab +Trastuzumab + Paclitaxel	Pertuzumab: 840 mg IV on day 1 followed by 420 mg IV Cycled every 21 days Trastuzumab: 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV on day 1 every 21 days Paclitaxel: 80 mg/m² IV on day 1 weekly or Paclitaxel: 175 mg/m² IV on day 1 Cycled every 21 days
Trastuzumab + Capecitabine	Trastuzumab: 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV every 21 days Capecitabine: 1,000-1,250 mg/m² PO 12 hourly on days 1-14 cycled every 21 days
Trastuzumab + Docetaxel	Trastuzumab: 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV every 21 days Docetaxel: 80-100 mg/m² IV on day 1 cycled every 21 days or Docetaxel: 35 mg/m² IV on days 1, 8, and 15 weekly cycled every 28 days
Trastuzumab + Paclitaxel	Trastuzumab: 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV every 21 days Paclitaxel: 175 mg/m² IV on day 1 cycled every 21 days or Paclitaxel: 80-90 mg/m²IV on day 1 weekly
Trastuzumab + Vinorelbine	Trastuzumab: 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or Trastuzumab: 8 mg/kg IV on day 1 followed by 6 mg/kg IV every 21 days Vinorelbine: 25 mg/m² IV on day 1 weekly or Vinorelbine: 20-35 mg/m² IV on days 1 and 8 Cycled every 21 days Vinorelbine: 25-30 mg/m² IV on days 1, 8 and 15 Cycled every 28 days
Tucatinib + Trastuzumab + Capecitabine	Tucatinib: 300 mg PO 12 hourly on days 1-21 Trastuzumab: 8 mg/kg IV day 1 followed by 6mg/kg IV day 1 every 21 days Capecitabine: 1,000 mg/m² PO 12 hourly on days 1-14 Cycled every 21 days

Cytotoxic Chemotherapy

Monotherapy Agents for Recurrent or Metastatic Breast Cancer

Drug	Dosage	Remarks
Capecitabine	1,000-1,250 mg/m² PO 12 hourly x 14 days Cycled every 21 days or 1,500 mg/m² PO 12 hourly on days 1-7 and 15-21 Cycled every 28 days	Adverse Reactions GI effects (diarrhea, nausea/vomiting, abdominal pain, stomatitis, constipation, dyspepsia, flatulence); Hematologic effects (neutropenia, anemia, lymphopenia); CNS effects (anorexia, insomnia, depression, headache, dizziness); Respiratory effects (nasopharyngitis, lower respiratory tract infection, rhinorrhea, cough, dyspnea); CV effect (edema); Other effects (fatigue, hand-foot syndrome, increased blood bilirubin) Special Instructions Contraindicated in patients with severe renal/hepatic impairment, dihydropyrimidine dehydrogenase deficiency, severe leukopenia, neutropenia or thrombocytopenia Use with caution in patients with renal impairment, mild-moderate hepatic dysfunction, galactose intolerance, patients taking oral coumarin-derivative anticoagulants Monitor ALT, AST, serum electrolytes
Chlorambucil	0.2 mg/kg/day PO x 6 weeks	Adverse Reactions GI effects (nausea/vomiting, diarrhea, hepatotoxicity); acute secondary hematologic malignancies; Rarely irreversible bone marrow failure, allergic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures, peripheral neuropathy, interstitial pulmonary fibrosis or pneumonia Special Instructions Avoid in first trimester pregnancy Use with caution in patients with renal or hepatic impairment, seizure disorder, patients immunized with live vaccine Monitor blood counts closely
Cyclophosphamide	50 mg PO 24 hourly on days 1-21 Cycled every 28 days	Adverse Reactions GI effects (nausea/vomiting, anorexia, mucositis); CNS effect (headache); GU effect (acute hemorrhagic cystitis or urinary fibrosis); Dermatologic effects (alopecia,rash); Hematologic effect (leukopenia); Respiratory effects (rhinorrhea, nasal congestion); Other effects (fertility impairment, renal tubular necrosis, SIADH may occur with doses >50 mg/kg) Special Instructions Use with caution in patients with hepatic or renal impairment
Docetaxel	60-100 mg/m² IV infusion over 1 hour Cycled every 21 days or 35 mg/m² IV infusion over 1 hour weekly x 6 weeks followed by 2 weeks rest period, then repeat	Adverse Reactions Ophthalmologic effect (epiphora with canalicular stenosis); CNS effects (paresthesia, dysesthesia); Dermatologic effects (alopecia, rash, erythema, desquamation, anaphylaxis); GI effects (nausea/vomiting, stomatitis, diarrhea); CV effects (hypotension, edema); Hematologic effects (neutropenia, leukopenia, anemia, thrombocytopenia); Other effects (weakness, bronchospasm, increased transaminases, pain) Special Instructions Premedication with corticosteroids, Diphenhydramine and H₂ antagonist is required for all patients Contraindicated in patients with preexisting bone marrow suppression with neutrophil count of <1,500 cells/mm³, and patients with hepatic impairment
Doxorubicin	60-75 mg/m² BSA IV every 21 days or 20 mg/m² IV weekly	Adverse Reactions Dermatologic effects (injection site reaction, alopecia, urticaria, rash); GI effects (nausea/vomiting, stomatitis, GI ulceration, diarrhea, loss of appetite); GU effects (urinary frequency, hematuria); Hematologic effects (leukopenia, anemia, thrombocytopenia); CV effects (transient ECG abnormalities, CHF); Other effects (discoloration of body fluids, hyperuricemia, infertility) Special Instructions Avoid in patients with preexisting bone marrow suppression and CHF Use with caution in patients with previous radiation therapy Baseline cardiac evaluation (ECG, LVEF) is advised especially in patients at high risk of cardiac toxicity May cause secondary leukemia
Doxorubicin (Pegylated liposomal)	50 mg/m² BSA IV infusion over 60 minutes every 4 weeks as long as patients do not progress and continue to tolerate treatment Initial dose administered at ≤1 mg/min to minimize infusion reactions 250 mL dextrose 5% in water dilution for <90 mg 500 mL dextrose 5% in water dilution for≥90 mg Cycled every 28 days
Epirubicin	60-90 mg/m² IV on day 1 Cycled every 21 days as monotherapy	Adverse Reactions CNS effect (changes in sensorium); Dermatologic effects (injection site reaction, alopecia, anaphylaxis, rash); GI effects (nausea/vomiting, diarrhea, loss of appetite); Hematologic effects (leukopenia, anemia, thrombocytopenia); Other effects (fever, menstrual dysfunction, hot flushes) Special Instructions Avoid in patients with cardiac disease (severe myocardial insufficiency, severe arrhythmias and recent MI) and in patients with baseline neutrophil count 1,500 cells/mm³ Use with caution in patients with preexisting cardiac disease, hepatic and renal dysfunction and in patients who have previously received anthracyclines May cause secondary leukemia
Eribulin	1.4 mg/m² IV on days 1 and 8 Cycled every 21 days	Adverse Reactions Hematologic effects (neutropenia, leukopenia, anemia); CNS effects (peripheral neuropathy, headache); GI effects (nausea/vomiting, constipation, diarrhea); Musculoskeletal effects (arthralgia, back pain, myalgia, pain in extremity); Other effects (asthenia, fatigue, pyrexia, decreased weight, alopecia, cough, dyspnea) Special Instructions Use with caution in patients with myelosuppression Correct hypokalemia, hypocalcemia and hypomagnesemia prior to treatment
Gemcitabine	800-1,200 mg/m² IV infusion over 30 minutes on days 1, 8 and 15 Cycled every 28 days	Adverse Reactions CV effect (edema); GI effects (diarrhea, paralytic ileus, nausea/vomiting); Dermatologic effects (rash, alopecia, pruritus); Hepatic effects (elevated liver enzymes and total bilirubin level); Other effects (bone marrow suppression, hemolytic uremic syndrome, pain, fever) Special Instructions Use with caution in patients with hepatic metastasis, hepatic or renal impairment, with concurrent radiation therapy
Idarubicin	45 mg/m² PO 24 hourly or 15 mg/m² PO 24 hourly x 3 days To be repeated every 3-4 weeks based on hematological recovery	Adverse Reactions GI effects (nausea/vomiting, diarrhea, abdominal pain, GIT bleeding, elevation of liver enzymes and bilirubin); CV effects (bradycardia, sinus tachycardia, tachyarrhythmia, asymptomatic reduction of LVEF, CHF, local phlebitis, thrombophlebitis); Other effects (decreased blood cell counts, red coloration of urine 1-2 days after treatment, rash, itch, fever) Special Instructions Use with caution in patients with secondary leukemia, galactose intolerance, Lapp-lactase deficiency, glucose-galactose malabsorption; increased susceptibility to infections Monitor hematologic profiles, cardiac, hepatic and renal function prior and during treatment Avoid in patients with uncontrolled infection, persistent myelosuppression, severe renal and hepatic impairment, severe myocardial insufficiency, recent MI, severe arrhythmias
Ifosfamide	Fractionated administration: 50-60 mg/kg/day IV x 5 days (total dose/cycle: 250-300 mg/kg) at 3-4 week intervals or 125-200 mg/kg/day single IV infusion	Adverse Reactions GI effects (nausea/vomiting); Other effects (myelosuppression, hemorrhagic cystitis, renal tubular and glomerular dysfunction, encephalopathy, alopecia) Special Instructions Use with caution in patients with previous radiotherapy, chronic hepatic and renal impairment, diabetes mellitus, brain metastases, cerebral symptoms, deteriorated renal function; always administer with uroprotective agent Mesna Avoid in patients with severely impaired bone marrow function, florid infections, impaired kidney function and/or urinary tract obstruction, cystitis
Ixabepilone	40 mg/m² IV infusion over 3 hours on day 1 Cycled every 21 days	Adverse Reactions GI effects (nausea/vomiting, diarrhea, stomatitis, mucositis); Hematologic effects (neutropenia, leukopenia, thrombocytopenia); Other effects (peripheral sensory neuropathy, myalgia, arthralgia,fatigue, asthenia, alopecia, musculoskeletal pain) Special Instructions Use with caution in patients with diabetes mellitus, history of cardiac disease, AST or ALT >5 or bilirubin >3 x upper limit of normal Monitor peripheral blood counts and for neuropathy symptoms Contraindicated in patients with history of severe hypersensitivity to agents containing Cremophor EL or its derivatives, neutrophils <1,500 cells/mm³ or platelet count <100,000 cells/mm³
Melphalan	0.15 mg/kg body wt or 6 mg/m² BSA/day PO for 5 days and repeated every 6 weeks	Adverse Reactions Dermatologic effects (rashes, hypersensitivity, skin ulceration, necrosis, alopecia); GI disturbances, pulmonary fibrosis, hemolytic anemia, bone marrow depression, myalgia, flu-like symptoms Special Instructions Use with caution in pregnancy, in patients with renal impairment, and in those who have just received radiotherapy or cytotoxic agents Monitor blood counts Contraindicated in lactating women
Mitomycin	Intermittent administration: 4-6 mg IV 24 hourly 1-2 times weekly Continuous administration: 2 mg IV 24 hourly Large dose intermittent administration: 10-30 mg IV 24 hourly at 1-3 weeks intervals	Adverse Reactions GI effects (nausea/vomiting, gastritis, diarrhea); Hematologic effects (thrombocytopenia, leukopenia, anemia); Other effects (renal failure, hypertension, edema, hematuria, hemolytic-uremic syndrome, marrow depression, interstitial pneumonia) Special Instructions Observe for evident renal toxicity Monitor patient frequently with lab tests, infectious disease, bleeding tendency Avoid in patients with thrombocytopenia, coagulation disorder, or increased bleeding tendencies, hepatic failure, renal impairment and bone marrow suppression
Mitoxantrone	14 mg/m² BSA single IV dose May be repeated after 21 days	Adverse Reactions GI effects (nausea/vomiting, diarrhea, abdominal pain, anorexia, constipation); CV effects (asymptomatic decrease in LVEF, transient ECG changes, arrhythmia); CNS effects (somnolence, neuritis, confusion, anxiety, paresthesia); Other effects (transient leukopenia, thrombocytopenia, anemia; bluish discoloration of sclerae, urine, or skin and nails, cramps) Special Instructions Use with caution in patients with history of anthracycline therapy, changes in cardiac function, severe hepatic insufficiency Monitor blood count during treatment Avoid in patients with severe bone marrow suppression
Paclitaxel (Albumin-bound)	260 mg/m² IV infusion over 30 minutes Cycled every 21 days or 100 or 125 mg/m² IV on days 1, 8 and 15 Cycled every 28 days	Adverse Reactions CV effects (ECG abnormality, edema, hypotension); GI effects (nausea/vomiting); Hematologic effects (neutropenia, anemia); Hepatic effect (elevated liver enzymes); Other effects (candidiasis infection, vision disturbances, sensory neuropathy) Special Instructions Premedication with corticosteroids, Diphenhydramine and H₂ antagonist is required for all patients Use with caution in patients with hepatic dysfunction
Paclitaxel (Conventional)	175 mg/m² IV infusion over 3 hours Cycled every 21 days or 80 mg/m² IV infusion over 1 hour weekly	Adverse Reactions Dermatologic effects (rash, alopecia, injection site reaction, hypersensitivity reaction); CV effects (edema, flushing, bradycardia); GI effects (nausea/vomiting, stomatitis, mucositis, diarrhea); Hematologic effects (neutropenia, leukopenia); Hepatic effect (elevated liver enzymes); Other effect (peripheral neuropathy) Special Instructions Premedication with corticosteroids, Diphenhydramine and H₂ antagonist is required for all patients Use with caution in patients with hepatic dysfunction
Tegafur¹	800-1,200 mg/day PO in 2-4 divided doses In combination with Uracil: 300-600 mg/day PO in 2-3 divided doses	Adverse Reactions GI effects (nausea/vomiting, anorexia, diarrhea); Other effects (thrombocytopenia, malaise, pigmentation) Special Instructions Use with caution in patients with bone marrow depression, hepatic or renal disorders, infectious diseases, GI ulcer or hemorrhage, abnormal glucose tolerance, varicella
Vinblastine	3.7 mg/m² IV injection weekly Dose may be increased by 1.85 mg/m²at weekly intervals until desired effect is achieved or total number of leukocytes has decreased to 3,000/mm³ Max dose: 18.5 mg/m²	Adverse Reactions Dermatologic effects (skin reactions, alopecia); Other effects (leukopenia, GI upset, neurological effects, ischemic cardiotoxicity, SIADH) Special Instructions If leukopenia occurs, monitor patients carefully for infection until WBC count returns to normal Do not inject into an extremity with impaired circulation Avoid in patients with leukopenia or bacterial infection
Vincristine	0.4-1.4 mg/m² BSA IV weekly	Adverse Reactions Dermatologic effect (alopecia); CV effects (orthostatic hypotension or hypertension); CNS effects (depression, headache, insomnia); GI effects (anorexia, bloating, paralytic ileus); Other effect (fever) Special Instructions Give prophylaxis for constipation Use with caution in patients with hepatic impairment and preexisting neuromuscular disease
Vinorelbine	25 mg/m² IV weekly In combination therapy, dose may be the same but frequency reduced (eg day 1 and 8 or day 1 and 5 every 3 weeks) or 60 mg/m² BSA PO once weekly for first 3 doses then may increase dose to 80 mg/m² PO once weekly after third dose	Adverse Reactions CNS effect (fatigue); GI effects (constipation, paralytic ileus, nausea/vomiting); Hematologic effects (bone marrow suppression, severe granulocytopenia, leukopenia); Hepatic effects (elevated AST and total bilirubin level); Other effects (alopecia, injection site reaction, weakness) Special Instructions Use with caution in patients with ulcerated skin or cachexia Only used for IV infusion

¹Combination with Uracil is available. Please see the latest MIMS for specific formulations and prescribing information.

Oestrogens, Progesterones & Related Synthetic Drugs

Monotherapy Agents for Recurrent or Metastatic Breast Cancer

Drug

Dosage

Remarks

Conjugated estrogen

Palliative treatment:
10 mg PO 8 hourly x ≥3 months

Adverse Reactions

GI effects (abdominal pain, diarrhea, dyspepsia, nausea); CNS effects (asthenia, headache, depression, dizziness, insomnia, nervousness); Musculoskeletal effects (back pain, arthralgia, leg cramps, myalgia); Other effects (pharyngitis, rhinitis, upper respiratory tract infection, pruritus, breast pain, leukorrhea, vaginal hemorrhage, vaginal moniliasis, vaginitis)

Special Instructions

Use with caution in patients with increased risk of CV disorders or endometrial cancer; dementia, gallbladder disease, hypercalcemia, visual abnormalities, angioedema, elevated BP, hypertriglyceridemia, impaired liver function, hypothyroidism, fluid retention, ovarian cancer; exacerbation of endometriosis, asthma, DM, epilepsy, migraine, porphyria, SLE and hepatic hemangiomas
Avoid in patients with undiagnosed abnormal genital bleeding, known or suspected estrogen-dependent neoplasia or pregnancy, active or history of DVT, pulmonary embolism, arterial thromboembolic disease

Ethinylestradiol
(Ethinyl estradiol)

Palliative treatment:
0.1-1 mg PO 8 hourly

Disclaimer

All dosage recommendations are for non-elderly adults with normal renal and hepatic function unless otherwise stated.
Not all products are available or approved for above use in all countries.
Products listed in the Drug Summary are based on indications stated in the locally approved product monographs.
Please refer to local product monographs in Related MIMS Drugs for country-specific prescribing information.

Breast Cancer Drug Summary

Agent Affecting Bone Metabolism

Anabolic Agent

Androgens & Related Synthetic Drugs

Cancer Hormone Therapy

Targeted Cancer Therapy

Combination Therapy Regimens

Cytotoxic Chemotherapy

Oestrogens, Progesterones & Related Synthetic Drugs

Disclaimer

Related MIMS Drugs