| Abstract: |
Purpose: Dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel and trastuzumab (PT) is feasible. Lapatinib is effective in the treatment of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer. We conducted a pilot study of dose-dense AC followed by PT plus lapatinib (PTL) followed by trastuzumab plus lapatinib (TL). Patients and Methods: Patients with stages I to III, HER2-positive breast cancer and left ventricular ejection fraction (LVEF) of ≥ 50% were enrolled. Treatment consisted of AC (60 mg/m2 and 600 mg/m2) for 4 cycles every 2 weeks (with pegfilgrastim 6 mg on day 2) followed by paclitaxel (80 mg/m2) for 12 doses weekly plus trastuzumab and lapatinib. Trastuzumab (4 mg/kg loading dose, then 2 mg/kg weekly during paclitaxel then 6 mg/kg every 3 weeks after paclitaxel) and lapatinib (1,000 mg daily) were given for 1 year. The primary end points were feasibility defined as ≥ 80% patients completing the PTL phase without a dose delay/reduction and a cardiac event rate of ≤ 4%. Results: From March 2007 to April 2008, we enrolled 95 patients. Median age was 46 years (range, 28 to 73 years). At a median follow-up of 22 months, 92 were evaluable. Of the 92 patients, 41 patients (45%) withdrew for PTL-specific toxicities. Overall, 40 (43%) of 92 patients had lapatinib dose reductions, and 27 (29%) of 92 patients had grade 3 diarrhea. Three patients (3%) had congestive heart failure; three patients dropped out because of significant asymptomatic LVEF decline during PTL followed by TL. Conclusion: Dose-dense AC followed by PTL and then followed by TL was not feasible because of a high rate of lapatinib dose reduction, mostly caused by unacceptable grade 3 diarrhea. Lapatinib (1,000 mg/d) was not feasible combined with weekly PT. © 2010 by American Society of Clinical Oncology. |
| Keywords: |
adult; treatment outcome; treatment response; aged; middle aged; survival rate; major clinical study; genetics; clinical trial; constipation; fatigue; neutropenia; doxorubicin; diarrhea; dose response; drug dose reduction; drug withdrawal; side effect; paclitaxel; cancer staging; follow up; follow-up studies; antineoplastic agent; neoplasm staging; metabolism; in situ hybridization, fluorescence; gene overexpression; drug eruption; multiple cycle treatment; pain; phase 2 clinical trial; sensory neuropathy; neoplasm recurrence, local; breast cancer; gene amplification; anemia; leukopenia; mucosa inflammation; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; myalgia; qt prolongation; epidermal growth factor receptor 2; cyclophosphamide; pathology; dose-response relationship, drug; breast neoplasms; monoclonal antibody; arthralgia; dizziness; dyspnea; febrile neutropenia; fever; loading drug dose; pneumonia; enzyme immunoassay; immunoenzyme techniques; hospitalization; antibodies, monoclonal; fluorescence in situ hybridization; feasibility study; pilot study; feasibility studies; pilot projects; chemically induced disorder; tumor recurrence; breast tumor; acne; receptor, erbb-2; headache; trastuzumab; recombinant granulocyte colony stimulating factor; virus hepatitis; dyspepsia; heart left ventricle ejection fraction; quinazolines; congestive heart failure; lapatinib; quinazoline derivative; paronychia; cellulitis; filgrastim; acneiform; heart rate; skin pruritus
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