Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure

Abstract

This multicentre, randomised phase III study compared docetaxel with 5-fluorouracil+vinorelbine in patients with metastatic breast cancer after failure of neo/adjuvant or one line of palliative anthracycline-based chemotherapy. One hundred and seventy-six metastatic breast cancer patients were randomised to receive docetaxel (100 mg m ) D1 and D5 of each 3-week cycle. Eighty-six patients received 516 cycles of docetaxel; 90 patients received 476 cycles of 5-fluorouracil+vinorelbine. Median time to progression (6.5 vs 5.1 months) and overall survival (16.0 vs 15.0 months) did not differ significantly between the docetaxel and 5-fluorouracil+vinorelbine arms, respectively. Six (7%) complete responses and 31 (36%) partial responses occurred with docetaxel (overall response rate 43%, 95% confidence interval: 32 -53%), while 4 (4.4%) complete responses and 31 (34.4%) partial responses occurred with 5-fluorouracil+vinorelbine (overall response rate 38.8%, 95% confidence interval: 29 -49%). Main grade 3 -4 toxicities were (docetaxel vs 5-fluorouracil+vinorelbine): neutropenia 82% vs 67%; stomatitis 5% vs 40%; febrile neutropenia 13% vs 22%; and infection 2% vs 7%. There was one possible treatment-related death in the docetaxel arm and five with 5-fluorouracil+vinorelbine. In anthracycline-pretreated metastatic breast cancer patients, docetaxel showed comparable efficacy to 5-fluorouracil+vinorelbine, but was less toxic. Metastatic breast cancer (MBC) is sensitive to chemotherapy but remains incurable with current therapeutic approaches. Single agents such as doxorubicin or epirubicin, cyclophosphamide, 5-fluorouracil (5-FU) and methotrexate achieve overall response rates (ORRs) ranging from 20 to 50% in this setting (Henderson et al, 1987;Clavel and Catimel, 1993). Combinations of alkylating agents with anthracyclines are extensively used in MBC and yield ORRs ranging from 40 to 60%, with complete response rates 520%, and a median response duration 515 months (The French Epirubicin Study Group, 1991;Brufman et al, 1997;Del Mastro et al, 2001).Use of anthracyclines is associated with problems of cumulative cardiotoxicity and primary or secondary resistance. As a result, there is a limit to the cumulative dose and number of regimens that can be administered to any given patient. Subsequent therapy in case of treatment failure is, therefore, a problem. Single-agent docetaxel has been proposed as an alternative treatment for patients previously treated with anthracyclinebased therapy; the efficacy of this drug has been demonstrated in pretreated patients with MBC (Ravdin et al, 1995;Valero et al, 1995;Nabholtz and Crown, 1998;Alexopoulos et al, 1999;Brodowicz et al, 2000).In patients with anthracycline-resistant MBC, docetaxel (100 mg m 72 ), infused over 1 h every 3 weeks, induces ORRs ranging from 30 to 69% (Ravdin et al, 1995;Valero et al, 1995;Nabholtz and Crown, 1998;Alexopoulos et al, 1999;Brodowicz et al, 2000).Single-agent vinorelbine, in second-line or salvage chemotherapy for MBC, has a reported response rate of ...

Activity and Safety of Vinorelbine Combined with Doxorubicin or Fluorouracil as First-Line Therapy in Advanced Breast Cancer: A Stratified Phase II Study

“…The high incidence of grade 3 or 4 neutropenia on day 15 was probably attributable to the administration of a second dose of vinorelbine on day 5 or 8 if the granulocyte count was 500 to 1,000 cells/mm 3 , but this was not usually associated with complications. Nearly universal grade 3 or 4 granulocytopenia has also been reported in other studies involving vinorelbine plus either doxorubicin [19] or fluorouracil [15,22,23], which was sometimes associated with neutropenic fever but rarely with the need for hospitalization. The risk of granulocytopenia associated with these combination regimens can be minimized by coadministration of antibiotics or hematopoietic growth factors [20,24], which were not used prophylactically in the current study.…”

A systematic review of taxane-containing regimens for metastatic breast cancer

“…A similar but nonsignificant effect was seen if trials with potentially suboptimal comparators (those comparing taxane with mitomycin7vinblastine, and fluorouracil with vinorelbine) (Dieras et al, 1995;Nabholtz et al, 1999;Bonneterre et al, 2002) were excluded (HR 0.97, 95% CI 0.88 -1.08, P ¼ 0.62), or if the analysis of this subgroup was limited to trials of first-line chemotherapy (HR 0.95, 95% CI 0.83 -1.10, P ¼ 0.50).…”

“…We identified 21 eligible studies, of which three are ongoing (Table 2) (Dieras et al, 1995;Bishop et al, 1999;Chan et al, 1999;Nabholtz et al, 1999Nabholtz et al, , 2003Sjostrom et al, 1999;Luck et al, 2000;Paridaens et al, 2000;Bonneterre et al, 2001Bonneterre et al, , 2002Bonneterre et al, , 2003Jassem et al, 2001;Zielinski et al, 2001;Biganzoli et al, 2002;Icli et al, 2002;Talbot et al, 2002;Bontenbal et al, 2003;Sledge et al, 2003;Goldhirsch, 2005;Heidemann, 2005). An additional two studies were identified but excluded: the status of one as a randomised trial was unclear (Gebbia et al, 2003), and the second randomised women to cease vs continue paclitaxel (Gennari et al, 2001).…”

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

“…Recently, taxanes became the standard treatment for these patients following anthracycline failure. In randomised trials, docetaxel (Taxotere s ) was found comparable to 5-fluorouracil þ vinorelbine (FUN) and more active than mitomycin C þ vinblastine (MV), and methotrexate þ 5-fluororacil (MF) in this group of patients (Nabholtz et al, 1999;Sjöström et al, 1999;Bonneterre et al, 2002). However, there are limited numbers of randomised trials comparing the efficacy of paclitaxel to other drugs or combination CTs in anthracycline-pretreated patients.…”