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

• Published in: Breast cancer research and treatment 2012, Vol.131 (1), p.127-135
• Main Authors: Lortholary, Alain, Hardy-Bessard, Anne-Claire, Bachelot, Thomas, de Rauglaudre, Gaëtan, Alexandre, Jérôme, Bourgeois, Hugues, Jaubert, Dominique, Paraiso, Désiré, Largillier, Rémy
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Agents, Phytogenic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Cancer; Cancer research; Cancer therapies; Capecitabine; Care and treatment; Chemotherapy; Clinical Trial; Clinical trials; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug Administration Schedule; Drug dosages; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - analogs & derivatives; Fluorouracil - therapeutic use; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Metastasis - drug therapy; Oncology; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Paclitaxel - therapeutic use; Treatment Outcome; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-011-1776-8

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.