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Dose-dense chemotherapy combined with dual HER-2 targeting agents not feasible
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Dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab plus lapatinib was not feasible due to unacceptable grade-3 diarrhea, according to the findings from a phase 2 study.
Researchers enrolled 95 patients with stages I to III, HER-2–positive breast cancer and left ventricular ejection fraction of at least 50%. Patients were assigned dose-dense doxorubicin and cyclophosphamide for four cycles every 2 weeks, followed by paclitaxel for 12 doses weekly plus trastuzumab (Herceptin, Genentech), and lapatinib (Tykerb, SmithKline Beecham) 1,000 mg daily. Ninety-two patients were evaluable.
Feasibility was defined as 80% of patients completing the paclitaxel plus trastuzumab plus lapatinib phase of treatment without a dose delay/reduction and a cardiac event rate of 4% or less.
Twenty-nine percent of patients had grade-3 diarrhea; 24% had it within the first week and 70% had it within the first cycle of treatment. Overall, 43% of patients had a lapatinib dose reduction, with 75% of patients having grade-3 diarrhea or unacceptable grade-2 or less.
Because of a more than 20% lapatinib dose reduction, the study was closed. Forty-five patients withdrew because of toxicities related to paclitaxel plus trastuzumab plus lapatinib, followed by trastuzumab plus lapatinib, with 59% having grade-3 diarrhea or unacceptable grade-2 or less despite active diarrhea management.
Three patients had grade-3 rash and four patients had grade-2 unacceptable rash. Three patients had congestive heart failure and three dropped out because of asymptomatic left ventricular ejection fraction decline.
“As we strive to improve outcomes through the addition of new targeted agents, it remains critically important to establish feasibility and provide guidance for the management of toxicities through phase 2 studies,” the researchers wrote.
For more information:
- Dang C. J Clin Oncol. 2010;doi:10.1200/JCO.2009.26.5900.