weekly vs every 3 week therapy TCH for metastatic BC

Don't just read the last line!

Even though numbers were small, overall survival was almost one year longer, response rate higher and side effects were fewer! Perhaps one gets the added "metronomic effect" of chemotherapy ie, smaller amounts given more often affect not only quickly dividing tumor cells but also the "ACHILLES HEEL"/WEAKEST LINK, the endothelial cells of the newly formed blood vessels feeding the tumor/mets.

ABSTRACT: Two Concurrent Phase II Trials of Paclitaxel/Carboplatin/Trastuzumab (Weekly or Every-3-Week Schedule) as First-Line Therapy in Women with HER2-Overexpressing Metastatic Breast Cancer: NCCTG Study 983252 [Clinical Breast Cancer]

Purpose: The efficacy and tolerability of 2 different schedules of paclitaxel/carboplatin/trastuzumab for HER2-overexpressing metastatic breast cancer (MBC) were evaluated in this parallel multicenter phase II trial.

Patients and Methods: Patients received every-3-week therapy (n = 43) consisting of a 200 mg/m2 dose of paclitaxel/carboplatin area under the curve (AUC) of 6 mg/mL per minute and trastuzumab (an initial 8 mg/kg dose and subsequent 6 mg/kg doses) administered every 21 days for 8 cycles or weekly therapy (n = 48) consisting of an 80-mg/m2 dose of paclitaxel/carboplatin AUC of 2 mg/mL per minute for 3 of 4 weeks, with weekly trastuzumab (an initial 4-mg/kg dose and subsequent 2-mg/kg doses) administered every 4 weeks for 6 cycles. Trastuzumab was continued until disease progression or unacceptable toxicity. HER2 status was confirmed by a central laboratory review.

Results: The overall response rate (ORR) with every-3-week therapy was 65% (90% confidence interval [CI], 51%-77%), with a median time to disease progression of 9.9 months and median overall survival (OS) time of 2.3 years. The ORR with weekly therapy was 81% (90% CI, 70%-90%), with a median time to disease progression of 13.8 months and a median OS time of 3.2 years. Hematologic and nonhematologic toxicities occurred significantly less frequently with weekly therapy versus every-3-week therapy: grade 3/4 neutropenia (52% vs. 88%); grade 3 thrombocytopenia (4% vs. 30%); and grade 3 neurosensory toxicity (2% vs. 19%), respectively.

Conclusions: Every-3-week and weekly regimens of paclitaxel/carboplatin/trastuzumab are highly active in women with HER2-overexpressing MBC. However, fewer patients developed severe neutropenia, leukopenia, or thrombocytopenia with the weekly schedule.