Cyclophosphamide and fluorouracil combined with mitoxantrone versus doxorubicin for breast cancer: superiority of doxorubicin.

1997 May

Journal Article

Authors:

Secondary:
J Clin Oncol

Volume:
15

Pagination:
1897-905

Issue:
5

PMID:
9164200

DOI:
10.1200/JCO.1997.15.5.1897

Keywords:
Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Middle Aged; Mitoxantrone; Survival Analysis

Abstract:
<p>PATIENTS AND METHODS: We conducted a randomized, multicenter study of intravenous cyclophosphamide 500 mg/m2 plus fluorouracil 500 mg/m2 combined with either mitoxantrone (Novantrone, Lederle Cyanamid Canada Ltd, Willowdale, Ontario) 10 mg/m2 (CNF) or doxorubicin (Adriamycin, Adria Laboratories of Canada Ltd, Mississauga, Ontario) 50 mg/m2 (CAF) every 3 weeks in advanced breast cancer.RESULTS: The response rate in 249 randomized patients was 36% with CNF (44 of 121) and 48% with CAF (62 of 128) (P = .054), with complete remissions in 10 patients (8.3%) on CNF and in 13 (10.2%) on CAF. If only fully assessable patients are considered, the response rate was 48% (44 of 91) with CNF and 60% (62 of 103) with CAF (P = .098). At time of analysis, all except 10 patients (one CNF and nine CAF) had died. The median survival time with CAF was longer than with CNF (15.2 v 10.9 months; P = .003), and time to progression was also longer with CAF (5.3 v 3.2 months; P &lt; .03). Survival differences remained significant (P = .006) if patients who failed to meet all eligibility criteria were excluded. Favorable prognostic factors for survival in a Cox regression model included good performance status (P &lt; .0001); less than two organ systems involved by tumor (P &lt; .0001); no involvement of lung, liver, or brain (P &lt; .003); involvement of bone or bone marrow (P &lt; .009), prior surgery for breast cancer (P &lt; .006); being premenopausal (P &lt; .03); &gt; or = 3 years from diagnosis until randomization on this study (P &lt; .03); and treatment with CAF (P &lt; .03). Alopecia &gt; or = grade 3 was reported in 55% of patients with CAF and 12% of patients with CNF (P &lt; .001), while other &gt; or = grade 3 toxicities did not differ significantly. Priestman-Baum quality-of-life assessment was comparable on the two study arms.CONCLUSION: In patients with advanced breast cancer, CAF was associated with longer survival than was CNF, with an increase in alopecia, but not in other toxicities.</p>