Adjuvant CMFVP versus melphalan for operable breast cancer with positive axillary nodes: 10-year results of a Southwest Oncology Group Study.

Abstract

Four hundred forty-one women with operable breast cancer with histologically positive axillary nodes were randomized to receive either combination cyclophosphamide (60 mg/m2 orally everyday for 1 year); fluorouracil (300 mg/m2 intravenously [IV] weekly for 1 year); methotrexate (15 mg/m2 IV weekly for 1 year); vincristine (0.625 mg/m2 IV for 10 weeks); prednisone (30 mg/m2 orally days 1 to 14, 20 mg/m2 days 15 to 28, 10 mg/m2 days 29 to 42) (CMFVP) or single-agent melphalan (L-PAM) (5 mg/m2 orally every day for 5 days every 6 weeks for 2 years) chemotherapy after a modified or radical mastectomy between January 1975 and February 1978. Patients were stratified according to menopausal status and number of positive nodes (one to three, more than three nodes) before randomization. Seventy-eight patients were ineligible, most (56) because they were registered more than 42 days from surgery. Maximum duration of follow-up is 12 years, with a median of 9.8 years. The treatment arms were balanced with respect to age, menopausal status, and number of positive nodes. Among eligible patients, disease-free survival and survival were superior with CMFVP (P = .002, .005, respectively). At 10 years, 48% of patients treated with CMFVP remain alive and disease-free and 56% remain alive, compared with 35% alive and disease-free and 43% alive on the L-PAM arm. Disease-free survival and survival were significantly better with CMFVP compared with L-PAM only in premenopausal patients and patients with four or more positive nodes. Both regimens were well tolerated, although toxicity was more severe and more frequent with CMFVP. We conclude that after 10 years of follow-up, adjuvant combination chemotherapy with CMFVP is superior to single-agent L-PAM in patients with axillary node-positive primary breast cancer. The major advantage is in premenopausal women and in patients with more than three positive axillary nodes.

Proportional hazards and recursive partitioning and amalgamation analyses of the southwest oncology group node-positive adjuvant CMFVP breast cancer data base: a pilot study

“…The identical adjuvant chemotherapy arm in each trial was CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone), with drugs given weekly for one year, as described in detail elsewhere [12]. Patients were registered no later than 42 days after definitive surgery.…”

“…A data base was formed of patients with nodepositive breast cancer enrolled on an identical treatment arm from each of the first four phase III adjuvant trials of the SWOG from January 1975 to July 1989 (SWOG-7436, and SWOG-7827A, B, and C) [ 12,[22][23][24]. Patients randomized to the other arm(s) in each trial were excluded from this Recursive partitioning and amalgamation analyses 275 prognostic factor analysis to avoid the possible confounding effect of different adjuvant therapy.…”

“…Multivariate analyses to evaluate the independent survival impact of these various prognostic factors were included in many first and second generation adjuvant therapy reports [12][13][14][15][16][17]. Again, results were uniform regarding the independent predictive value of number of positive nodes, but they were inconclusive regarding ER and PgR status, menopausal status, and age.…”

“…The maturity of the first four node-positive adjuvant trials of the Southwest Oncology Group (SWOG) presented an opportunity to study the independent predictors of outcome without the confounding effect of different eligibility requirements or treatment [12,[22][23][24]. The oneyear CMFVP arm (defined below) was identically administered in each of the four studies.…”

A randomized trial of chemotherapy (L-PAM vs CMF) and irradiation for node positive breast cancer

“…Although CMF is superior to L-PAM for treatment of advanced disease [9], in the adjuvant setting, ten year follow-up of other randomized trials of L-PAM versus CMF is not yet available [10]. The Southwest Oncology Group (SWOG) recently published their 10 year analysis of L-PAM versus CMFVP in node positive women [11]. Relapse-free and overall survival were 35% and 43% for L-PAM and 48% and 56% for CMFVP, a statistically significant difference favoring the combination regimen.…”