title: A GINECO randomized phase II trial of two capecitabine and weekly paclitaxel schedules in metastatic breast cancer.
abstract: 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.
authors.affiliation: Centre Catherine de Sienne, 2 Rue Eric Tabarly, BP 20215, 44202 Nantes Cedex 2, France. lortholary.alain@catherinedesienne.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Hardy-Bessard
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Gaëtan
authors.initials: G
authors.lastname: de Rauglaudre
authors.forename: Jérôme
authors.initials: J
authors.lastname: Alexandre
authors.forename: Hugues
authors.initials: H
authors.lastname: Bourgeois
authors.forename: Dominique
authors.initials: D
authors.lastname: Jaubert
authors.forename: Désiré
authors.initials: D
authors.lastname: Paraiso
authors.forename: Rémy
authors.initials: R
authors.lastname: Largillier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D000069287:Capecitabine; D017239:Paclitaxel; D005472:Fluorouracil