Cycle length: Every 21 days. Duration of therapy: Prior to surgery (neoadjuvant portion of treatment), administer carboplatin, docetaxel, trastuzumab, and pertuzumab¶ every 21 days for six cycles. Following surgery, adjuvant treatment consists of 11 cycles of trastuzumab alone to complete one year of trastuzumab. | |||
Drug | Dose and route | Administration | Given on days |
Before surgery (neoadjuvant treatment) | |||
Trastuzumab (loading dose)Δ | 8 mg/kg IV | Dilute in 250 mL NS◊ and administer over 90 minutes. DO NOT mix with D5W and DO NOT infuse as an IV push or bolus. | Cycle 1: Day 1 |
TrastuzumabΔ | 6 mg/kg IV | Dilute in 250 mL NS◊ and administer over 30 minutes. DO NOT mix with D5W and DO NOT infuse as an IV push or bolus. | Cycles 2 to 6: Day 1 |
Pertuzumab (loading dose)Δ | 840 mg IV | Dilute in 250 mL NS◊ and administer over 60 minutes for the loading dose. DO NOT mix with D5W and DO NOT infuse as an IV push or bolus. | Cycle 1: Day 1 |
PertuzumabΔ | 420 mg IV | Dilute in 250 mL NS◊ and administer over 30 to 60 minutes. DO NOT mix with D5W and DO NOT infuse as an IV push or bolus. | Cycles 2 to 6: Day 1 |
Carboplatin | AUC§ = 6 mg/mL per min IV | Dilute in 250 mL NS◊ and administer over 30 minutes. | Cycles 1 to 6 only: Day 1 |
Docetaxel | 75 mg/m2 IV | Dilute in 250 mL NS◊ to a final concentration of 0.3 to 0.74 mg/mL and administer over 60 minutes. | Cycles 1 to 6 only: Day 1 |
After surgery (adjuvant treatment) | |||
Trastuzumab (loading dose)Δ | 8 mg/kg IV | Dilute in 250 mL NS◊ and administer over 90 minutes. DO NOT mix with D5W and DO NOT infuse as an IV push or bolus. | Cycle 7: Day 1 |
TrastuzumabΔ | 6 mg/kg IV | Dilute in 250 mL NS◊ and administer over 30 minutes for subsequent doses. DO NOT mix with D5W and DO NOT infuse as an IV push or bolus. | Cycles 8 to 17 to complete one year of trastuzumab: Day 1 |
Pretreatment considerations: | |||
Emesis risk |
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Prophylaxis for infusion reactions |
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Vesicant/irritant properties |
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Infection prophylaxis |
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Dose adjustment for baseline liver or renal dysfunction |
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Cardiopulmonary issues |
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Dose adjustment for known drug interactions |
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Monitoring parameters: | |||
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Suggested dose modifications for toxicity: | |||
Myelotoxicity |
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Hepatotoxicity |
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Cardiotoxicity |
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Pulmonary toxicity |
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Infusion reactions |
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Cutaneous, mucosal, and neurologic toxicity |
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If there is a change in body weight of at least 10%, doses should be recalculated. |
ANC: absolute neutrophil count; AUC: area under the concentration × time curve; CBC: complete blood count; CYP3A4: cytochrome P450 3A4; D5W: 5% dextrose in water; FISH: fluorescence in situ hybridization; GFR: glomerular filtration rate; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemical staining; IV: intravenous; LVEF: left ventricular ejection fraction; NCCN: National Comprehensive Cancer Network; NS: normal saline; NSAID: nonsteroidal anti-inflammatory drug; ULN: upper limit of normal.
* High levels of HER2 overexpression, as determined by either 3+ IHC or positive FISH, are used to select patients for therapy with trastuzumab and pertuzumab. Refer to UpToDate topic on "HER2 and predicting response to therapy in breast cancer".
¶ Administer trastuzumab, pertuzumab, carboplatin, and docetaxel sequentially, with carboplatin and docetaxel administered after trastuzumab and pertuzumab. During neoadjuvant treatment, wait 30 to 60 minutes following pertuzumab to begin carboplatin.[1]
Δ A repeat loading dose of trastuzumab is required if scheduled treatment has been delayed for over one week, which is the case for patients resuming trastuzumab after definitive surgery. If adverse reactions occur for which discontinuation of trastuzumab or pertuzumab is indicated, both drugs should be discontinued. Dose modifications of trastuzumab and pertuzumab were not allowed in the original protocol.[1]
◊ Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).
§ AUC is converted to a patient-specific carboplatin dose (in mg) according to the renal function by using the Calvert formula. The Calvert formula is total dose (mg) = (target AUC) × (GFR + 25). If using measured serum creatinine, limit the maximal GFR for the calculation to 125 mL/min. Refer to UpToDate topic on "Dosing of anticancer agents in adults".
¥ Consensus-based guidelines from the NCCN classify higher carboplatin doses (AUC ≥4) as highly emetogenic; by contrast, the American Society of Clinical Oncology and the Multinational Association for Supportive Care in Cancer guidelines consider all carboplatin doses to be moderately emetogenic. Although many institutions classify carboplatin-containing regimens as moderately emetogenic, a benefit for adding a neurokinin 1 receptor antagonist on day 1 has been shown in many studies; additional prophylaxis beyond day 1 for delayed emesis is not needed for most patients. Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
‡ A list of strong and moderate CYP3A4 inhibitors is available as a separate table in UpToDate. Specific interactions may be determined by use of the drug interactions program included within UpToDate.Do you want to add Medilib to your home screen?