Phase III Study of Gemcitabine Plus Docetaxel Compared With Capecitabine Plus Docetaxel for Anthracycline-Pretreated Patients With Metastatic Breast Cancer

• Published in: Journal of clinical oncology Vol. 27; no. 11; pp. 1753 - 1760
• Main Authors: CHAN, Stephen, ROMIEU, Gilles, MAYORDOMO, Jose Ignacio, ANTON, Antonio, HARRISON, Mark, JONES, Alison, CARRASCO, Eva, THAREAU VAURY, A, FRIMODT-MOLLER, Bente, FUMOLEAU, Pierre, HUOBER, Jens, DELOZIER, Thierry, TUBIANA-HULIN, Michele, SCHNEEWEISS, Andreas, LLUCH, Ana, LLOMBART, Antonio, DU BOIS, Andreas, KREIENBERG, Rolf
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.04.2009
• Subjects: Adult; Aged; Anthracyclines - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - secondary; Capecitabine; Combined Modality Therapy; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Survival Analysis; Taxoids - administration & dosage; Tumors; Antineoplastic agent; Phase III trial; Breast disease; Gemcitabine; Capecitabine; Metastasis; Cancerology; Taxane derivatives; Advanced stage; Antimitotic; Pyrimidine nucleoside; Human; Fluoropyrimidine derivatives; Docetaxel; Breast cancer; Malignant tumor; Prodrug; Mammary gland diseases; Treatment; Antimetabolic; Pyrimidine derivatives; Anthracyclins; Fluorine Organic compounds; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2007.15.8485

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 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. 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). 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.