Adjuvant, Neoadjuvant Regimen: Doxorubicin + Cyclophosphamide, then Paclitaxel + Trastuzumab, then Trastuzumab Alone (AC × 4 → TH × 12 Weeks → H × 40 Weeks)
Romond EH et al. N Engl J Med 2005;353:1673–1684
Seidman AD et al. J Clin Oncol 2001;19:2587–2595
AC (doxorubicin + cyclophosphamide) regimen
Hydration with 0.9% sodium chloride injection (0.9% NS); administer intravenously 500 mL before starting cyclophosphamide and 500 mL after completing cyclophosphamide administration
Doxorubicin HCl 60 mg/m2; administer by intravenous injection over 3–5 minutes on day 1, every 21 days for 4 cycles (total dosage/cycle = 60 mg/m2)
Cyclophosphamide 600 mg/m2; administer intravenously in 100–500 mL 0.9% NS or 5% dextrose injection (D5W) over 15–60 minutes on day 1, every 21 days for 4 cycles (total dosage/cycle = 600 mg/m2)
Supportive Care
Antiemetic prophylaxis
Emetogenic potential is HIGH. Potential for delayed symptoms
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is NOT indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Weekly TH (paclitaxel + trastuzumab) regimen
Schedule for first week of paclitaxel + trastuzumab
Trastuzumab 4 mg/kg (loading dose); administer intravenously in 250 mL 0.9% NS over at least 90 minutes, 1 day before the first dose of paclitaxel is administered (total trastuzumab dosage during the first treatment week = 4 mg/kg), followed 1 day later by:
Premedication for paclitaxel:
Dexamethasone 10 mg; administer intravenously 30–60 minutes before paclitaxel (total dose/cycle = 10 mg)
Note: Dexamethasone doses may be gradually reduced in 2- to 4-mg increments if a patient has no hypersensitivity reactions during repeated paclitaxel treatments
Diphenhydramine 50 mg; administer intravenously 30–60 minutes before paclitaxel
Cimetidine 300 mg (or ranitidine 50 mg, or famotidine 20 mg, or an equivalent histamine receptor [H2]-subtype antagonist); administer intravenously over 15 to 30 minutes, 30 to 60 minutes before starting paclitaxel administration
Paclitaxel 80 mg/m2; administer intravenously in a volume of 0.9% NS or D5W sufficient to produce a concentration within the range 0.3–1.2 mg/mL over 60 minutes (total dosage = 80 mg/m2)
Paclitaxel + trastuzumab during the second and subsequent weeks
Premedication for paclitaxel:
Dexamethasone 10 mg; administer intravenously 30–60 minutes before paclitaxel
Note: If a patient does not experience any manifestations of hypersensitivity or an allergic reaction after 8 paclitaxel infusions, the dexamethasone dose may be reduced as follows:
Diphenhydramine 50 mg; administer by intravenous injection 30–60 minutes before paclitaxel
Cimetidine 300 mg (or ranitidine 50 mg, or famotidine 20 mg, or an equivalent histamine receptor [H2]-subtype antagonist); administer intravenously over 15–30 minutes, 30–60 minutes before starting paclitaxel administration
Paclitaxel 80 mg/m2 per week; administer intravenously in a volume of 0.9% NS or D5W sufficient to produce a concentration within the range 0.3–1.2 mg/mL over 60 minutes, weekly, for 11 weeks (total dosage/week = 80 mg/m2), followed immediately afterward by:
Trastuzumab 2 mg/kg per week; administer intravenously in 250 mL 0.9% NS over 30 minutes, weekly, for 11 weeks (total trastuzumab dosage/week during the second and later weeks = 2 mg/kg)
Note: The duration of trastuzumab administration may be decreased from an initial infusion duration of 90 to 30 minutes if administration over longer durations is well tolerated
Supportive Care
Antiemetic prophylaxis
Emetogenic potential is LOW
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is NOT indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Weekly H (trastuzumab) regimen
Trastuzumab 2 mg/kg per week; administer intravenously in 250 mL 0.9% NS over 30 minutes, weekly, for 40 weeks (total trastuzumab dosage/week = 2 mg/kg)
Supportive Care
Antiemetic prophylaxis
Emetogenic potential is MINIMAL
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is NOT indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Trastuzumab infusion reactions
A symptom complex most commonly consisting of chills and/or fever may occur in as many as 40% of patients during the first infusion of trastuzumab. These symptoms occur infrequently with subsequent trastuzumab infusions. Other signs and/or symptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache, dizziness, dyspnea, hypotension, rash, and asthenia. Although the symptoms are usually mild to moderate in severity, infrequently, trastuzumab may need to be discontinued
When such a symptom complex is observed it can be treated with or without reduction in the rate of trastuzumab infusion, and:
Acetaminophen 650 mg; administer orally
Diphenhydramine 25–50 mg; administer orally or by intravenous injection, and
Meperidine 12.5–25 mg; administer by intravenous injection every 10 minutes if needed for shaking chills (generally, cumulative doses >50 mg are not needed; use with caution in persons with moderate or more severely impaired renal function)
With or without reduction in the rate of trastuzumab infusion
Treatment Plan Notes:
Patient Population Studied
Romond EH et al. J Clin Oncol 2005;16:1673–1684: Report of two trials that treated 1672 women with a regimen of AC followed by paclitaxel with trastuzumab, followed by trastuzumab alone [AC → P + H → H]. Two studies were combined in one analysis: (a) National Surgical Adjuvant Breast and Bowel Project trial B-31 and (b) North Central Cancer Treatment Group trial N9831. Both trials enrolled women with a pathologic diagnosis of adenocarcinoma of the breast with immunohistochemical staining for HER2 protein of 3+ intensity or amplification of the HER2 gene on fluorescence in situ hybridization. Initially, required patients to have histologically proven, node-positive disease; subsequently, N9831 was amended to include patients with high-risk node-negative disease (defined as a tumor that was more than 2 cm in diameter and positive for estrogen receptors or progesterone receptors or as a tumor that was more than 1 cm in diameter and negative for both estrogen receptors and progesterone receptors). Other requirements included a left ventricular ejection fraction (LVEF) that met or exceeded the lower limit of normal. Complete resection of the primary tumor and axillary-node dissection were required (negative sentinel-node biopsy was allowed in trial N9831). Patients were ineligible if they had one of several cardiac risk factors