Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?

Abstract

BACKGROUND:

In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy.

PATIENTS AND METHODS:

Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered.

RESULTS:

More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles.

CONCLUSIONS:

Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.

• Authors: R Leonard, J O'Shaughnessy, S Vukelja, V Gorbounova, C A Chan-Navarro, D Maraninchi, N Barak-Wigler, J J McKendrick, W G Harker, A S Bexon, C Twelves
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 17 Issue 9 Pg. 1379-85 (Sep 2006) ISSN: 0923-7534 [Print] England
• PMID: 16966367 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Taxoids
• Deoxycytidine
• Docetaxel
• Capecitabine
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, mortality)
• Capecitabine
• Carcinoma (drug therapy, mortality)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Docetaxel
• Dose-Response Relationship, Drug
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Metastasis (drug therapy)
• Survival Analysis
• Taxoids (administration & dosage, adverse effects)
• Treatment Outcome