Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: A parallel dose-finding study

Abstract

SummaryPurpose: The objective of this study was to determine the docetaxel MTD when combined with gemcitabine or vinorelbine in advanced breast cancer patients who had received previous anthracycline-based chemotherapy for advanced disease.Patients and methods: Advanced breast cancer patients aged between 18 and 70 with ECOG PS 0-2 who had not responded to, or had relapsed after, first-line anthracycline-based chemotherapy, were randomized to receive either gemcitabine 1000 mg/m 2 or vinorelbine 25 mg/m 2 in combination with escalating doses of docetaxel (starting from 30 mg/m 2 ), all on days 1 and 8 every three weeks. Escalation was stopped if > 33% of patients treated at a given dose level showed DLTat the first cycle.Results: A total of 34 patients with locally advanced (8) or metastatic disease (26) were treated, for a total of 94 cycles delivered. Nineteen patients received docetaxel in combination with gemcitabine and 15 with vinorelbine. All patients had been pretreated with anthracyclines, and 24 of 34 had also received weekly dose-dense paclitaxel. A docetaxel dose of 40/m 2 proved to be safe when combined on days 1 and 8 with gemcitabine, while a dose of 35 mg/m 2 was tolerated in combination with vinorelbine. Overall, nine episodes of DLT, all of them neutropenia, occurred at the first cycle. Considering all 94 cyles, grades 3 or 4 neutropenia and thrombocytopenia occurred in 15 (44%), and 7 (20%) patients. Non-hematologic toxicity was mild, except for three cases of grade 2 peripheral neuropathy. All patients were assessed for response on an 'intent-to-treat' basis. Overall, five partial responses were recorded (docetaxel + gemcitabine = 3 and docetaxel + vinorelbine = 2), for a 15% (95% CI: 5%-31%) overall response rate. Only 1 of 24 (4%) patients who had received weekly dosedense paclitaxel responded to treatment. Conclusions:The weekly docetaxel administration in combination with either gemcitabine or vinorelbine is a well-tolerated treatment for heavily pretreated advanced breast cancer patients. This approach, although sometimes capable of achieving a major response, does not seem advisable in advanced breast cancer patients refractory to both anthracyclines and paclitaxel.

Biweekly Docetaxel-Irinotecan Treatment with Filgrastim Support Is Highly Active in Antracycline-Paclitaxel-Refractory Breast Cancer Patients

“…We have previously tested DTX in combination with either gemcitabine or vinorelbine administered on days 1 and 8 every 3 weeks. Both ORR and PFS were substantially worse than those observed in the present study [28]. …”

“…Of note, the chance of response and long-term survival in BC patients refractory to both anthracycline and paclitaxel treatment is very poor [3,26,27,28]. Moreover, it should be taken into account that a relevant number of patients had received even a second-line treatment for the metastatic disease.…”

Weekly Combination of Docetaxel and Vinorelbine in Metastatic Breast Cancer: A Phase I/II Study

“…Docetaxel and vinorelbine have already been tested in phase I combination clinical trials in ABC [4, 5] and non-small cell lung cancer [6,7,8]. However, these studies used different, although conventional, schedules; three studies administered docetaxel as a single dose every 3 weeks and vinorelbine as several doses [4, 6, 7].…”

Weekly Administration of Gemcitabine Plus Docetaxel in Patients with Advanced Breast Cancer: A Phase 1 Study

“…In these phase 1 or 1/2 studies, docetaxel was administered at various doses (from 40 to 100 mg/m 2 ) and schedules (mainly on day 8 only, every 3 weeks) [22, 23, 24, 25]. Only recently, a study examined a schedule in which docetaxel was administered on days 1 and 8, every 21 days [26]. The authors concluded that a docetaxel dose of 40 mg/m 2 using this 3-week schedule is safe when combined with gemcitabine at 1,000 mg/m 2 .…”