Phase III study of gemcitabine plus docetaxel compared with capecitabine plus docetaxel for anthracycline-pretreated patients with metastatic breast cancer.

Abstract

PURPOSE:

Patients with metastatic breast cancer who are pretreated with anthracyclines frequently receive taxane-based combinations. This phase III study compared the efficacy and safety of gemcitabine-docetaxel (GD) with capecitabine-docetaxel (CD) in advanced breast cancer.

PATIENTS AND METHODS:

Patients were randomly assigned to GD (G 1,000 mg/m(2) days 1 and 8; D 75 mg/m(2) day 1) or CD (C 1,250 mg/m(2) twice daily days 1 through 14; D 75 mg/m(2) day 1) every 21 days. Comparison of progression-free survival (PFS) was the primary objective.

RESULTS:

Patient characteristics were balanced between arms (N = 305). Median PFS was 8.05 months (95% CI, 6.60 to 8.71) for GD and 7.98 (95% CI, 6.93 to 8.77) for CD (log-rank P = .121). Overall response rate (ORR) was 32% in both arms, and overall survival (OS) was not different between arms (P = .983). Time to treatment failure (TTF; defined as discontinuation, progressive disease, death as a result of any cause, or the start of a new anticancer therapy) was superior in the GD arm (P = .059). Hematologic toxicity was similar in both arms, except for grades 3 to 4 leukopenia (GD, 78%; CD, 66%; P = .025) and transfusions (GD, 17%; CD, 7%; P = .0051). Grades 3 to 4 diarrhea, mucositis, and hand-and-foot syndrome were significantly higher in the CD arm. Fewer patients in the GD arm discontinued because of drug-related adverse events (13% v 27% in CD; P = .002).

CONCLUSION:

No difference was observed between GD and CD arms in PFS, ORR, and OS. TTF was longer in the GD arm. These findings, combined with a nonhematologic toxicity profile that favors GD over approved doses of CD, suggest that gemcitabine may be a better option than capecitabine in combination with docetaxel in this clinical setting.

• Authors: Stephen Chan, Gilles Romieu, Jens Huober, Thierry Delozier, Michele Tubiana-Hulin, Andreas Schneeweiss, Ana Lluch, Antonio Llombart, Andreas du Bois, Rolf Kreienberg, Jose Ignacio Mayordomo, Antonio Antón, Mark Harrison, Alison Jones, Eva Carrasco, A Thareau Vaury, Bente Frimodt-Moller, Pierre Fumoleau
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 11 Pg. 1753-60 (Apr 10 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19273714 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracyclines
• Taxoids
• Deoxycytidine
• Docetaxel
• Capecitabine
• Fluorouracil
• Gemcitabine

Topics

• Adult
• Aged
• Anthracyclines (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Breast Neoplasms (drug therapy, secondary)
• Capecitabine
• Combined Modality Therapy
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Docetaxel
• Female
• Fluorouracil (administration & dosage, analogs & derivatives)
• Humans
• Middle Aged
• Survival Analysis
• Taxoids (administration & dosage)
• Gemcitabine