A GINECO randomized phase II trial of two capecitabine and weekly paclitaxel schedules in metastatic breast cancer

Abstract

To determine whether capecitabine schedule adaptation improves the tolerability of capecitabine-paclitaxel combination therapy for metastatic breast cancer (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized to either arm A (21-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-14; paclitaxel 60 mg/m(2), days 1, 8, and 15) or arm B (28-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-5, 8-12, and 15-19; paclitaxel 80 mg/m(2), days 1, 8, and 15). The primary endpoint was the incidence of dose reductions or delays >1 week for grade 3/4 toxicity. Secondary endpoints were efficacy and safety. All 130 randomized patients were evaluable for safety. Dose reduction or delay for grade 3/4 toxicity occurred in 39% of patients in arm A and 34% in arm B during cycles 1-6. In arm A, there were significantly more toxicity-related dose reductions (cycles 1-6: 82 vs. 67%, respectively; P = 0.05) and discontinuations (29 vs. 8%, respectively). Grade 3 diarrhea occurred in 12 and 0%, respectively, and grade 3 hand-foot syndrome in 12 versus 9%, respectively (grade 4 not applicable). There were no detectable differences in efficacy. Weekday capecitabine dosing with weekly paclitaxel may improve tolerability without a detrimental effect on efficacy, and merits further evaluation in patients suited to combination chemotherapy.

Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first‐line therapy for triple‐negative, metastatic, or locally advanced breast cancer: Results from the GINECO A‐TaXel phase 2 study

“…It is interesting to note that grade 3 diarrhea was reported in only 6% of patients and grade 4 was absent; grade 3 hand‐foot syndrome occurred in 13% of patients. These incidences are similar to those for a weekday capecitabine regimen and paclitaxel reported in the TaXel study . The incidence of grade 3 hypertension was higher than in most other studies of bevacizumab‐containing therapy, but this well‐known side effect of bevacizumab was generally manageable, and resulted in temporary interruption of bevacizumab therapy in only 8% of patients.…”

“…These incidences are similar to those for a weekday capecitabine regimen and paclitaxel reported in the TaXel study. 10 The incidence of grade 3 hypertension was higher than in most other studies of bevacizumab-containing therapy, but this wellknown side effect of bevacizumab was generally manageable, and resulted in temporary interruption of bevacizumab therapy in only 8% of patients. One patient with documented DPD deficiency died.…”

“…11 The median PFS of 7.6 months with A-TaXel compares favorably with that in the subgroup of patients with TNBC (6.5 months) in our previously reported TaXel study. 10 The median PFS reported in the current study is shorter than that in subsets of patients with TNBC who were treated with slightly different regimens combining bevacizumab plus paclitaxel (both of which were continued until disease progression) in the E2100 (10.6 months) 14 or TURANDOT (9.0 months 15 ) trials, but compares favorably with the median PFS for other targeted agents and chemotherapy observed in subset analyses (range, 3.1-5.9 months) 16 and is similar to the efficacy recently reported from a small Chinese study evaluating first-line gemcitabine plus cisplatin therapy among 30 patients with TNBC. 17 The median OS of 19.2 months also suggests significant activity of the A-TaXel regimen.…”

“…9 In our previously published, randomized, phase 2 TaXel study, we demonstrated that weekly paclitaxel combined with an intermittent weekday capecitabine regimen (days 1-5 every week) is a tolerable and effective first-line treatment for patients with locally advanced/ metastatic breast cancer (LA/MBC), with notable efficacy in the subgroup of patients with TNBC (median progression-free survival [PFS] of 6.5 months). 10 A meta-analysis of the 3 pivotal, randomized, phase 3 trials of bevacizumab in the first-line setting of HER2negative MBC demonstrated that combining chemotherapy with bevacizumab improved the PFS rate, overall response rate (ORR), and 1-year overall survival (OS) rate compared with chemotherapy alone. 11 In retrospective subset analyses of patients with TNBC, bevacizumab plus chemotherapy was associated with a median PFS of 8.1 months, a median OS of 18.9 months, and a 1-year OS rate of 71% (compared with 65% in patients receiving chemotherapy alone).…”

Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer

“…In contrast to Btargeted^agents for chemotherapy it is widely accepted that higher dose results in higher treatment efficacy [24,25]. Investigations however suggested that altered schedules may lower side effects without affecting disease outcome [26,27] and interventions preventing side effects are recommended which may contribute to maintain dose intensity [28,29]. Interestingly, in a recent study reduced doses of cytotoxic drugs in combination with full dose of cetuximab (or bevacizumab) resulted in improved OS and quality of life for more than half of the patients with end-stage cholangiocarcinoma [30].…”