Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes. A southwest oncology group study

Abstract

The Southwest Oncology Group in a prospective randomized study compared one year of adjuvant combination chemotherapy with continuous CMFVP to two years of intermittent L‐PAM in women with operable breast cancer with histologically positive axillary lymph nodes. In fully evaluable patients with a 42‐month median and 30‐month minimum follow‐up, treatment failures have occurred in 26% of 145 receiving CMFVP and 47% of 167 women given L‐PAM (P = 0.002). Disease‐free survival times were significantly longer with CMFVP than with L‐PAM in the following subgroups: premenopausal women (P = 0.002), postmenopausal women (P = 0.002), women with 1–3 involved axillary nodes (P = 0.003), and women with four or more involved axillary nodes (P = 0.002). CMFVP was effective in pre‐ and postmenopausal women. There is a significant difference in survival in favor of CMFVP compared to L‐PAM (P = 0.005). The life table estimates of survival at 42 months are 86% for women on the CMFVP treatment arm and 73% for women on the L‐PAM treatment arm. There was no correlation between the interval from mastectomy to onset of chemotherapy (between one and six weeks) and recurrence rates. Acute toxicity with both treatment arms was moderate and reversible. These results show that continuous CMFVP is superior to intermittent L‐PAM in decreasing recurrences and increasing survival in both pre‐ and postmenopausal women with operable breast cancer with histologically involved axillary nodes.

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer

“…In a retrospective study on patients included in a randomized trial of adjuvant chemotherapy on nodepositive breast cancer, Bonadonna and Valagussa (1981) demonstrated a significant correlation between unscheduled dose reduction and reduced survival. Similar results have been published subsequently from many retrospective studies in early and advanced breast cancer (Rodriguez-Kraul et al, 1981;Tormey et al, 1983;Howell et al, 1984;Senn et al, 1984;Ang et al, 1989;Pronzato et al, 1989), however some retrospective studies have failed to demonstrate any significant correlation between dose and therapy efficacy (Ahmann et al, 1982;Glucksberg et al, 1982;Redmond et al, 1983;Mouridsen et al, 1984;Velez-Garcia et al, 1987). A series of analyses on published chemotherapy studies demonstrated that a positive correlation existed between the scheduled amount of drug per unit time and the efficacy of chemotherapy treatment on both early and advanced breast cancer (Hryniuk and Bush, 1984;Hryniuk and Levine, 1986).…”

Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF

“…Bonadonna and Valgussa found in 1981 that disease-free survival was shorter in node-positive breast cancer patients who received a reduced dose of adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) than in those who received full or nearly full dose (Bonadonna and Valagussa, 1981) Similar findings have been published in other retrospective studies in early and advanced breast cancer (Rodriguez et al, 1981;Tormey et al, 1983;Howell et al, 1984;Senn et al, 1984;Ang et al, 1989;Pronzato et al, 1989) while in some studies no significant correlation between the given dose and survival benefit was found (Ahmann et al, 1982;Glucksberg et al, 1982;Redmond et al, 1983;Mouridsen et al, 1984;Velez-Garcia et al, 1987). These studies have been criticized due to the bias inherent in this kind of retrospective analysis (Redmond et al, 1983).…”

Current status of adjuvant systemic therapy for primary breast cancer: progress and controversy

“…9 However, retrospective analyses of several clinical trials of adjuvant therapy have given conflicting results. 27, [66][67][68][69] In some, 66 patients who began adjuvant chemotherapy soon after definitive surgery had higher relapse-free and overall survival rates than those who started their adjuvant chemotherapy late in the postoperative period. However, in other retrospective analyses, this advantage could not be confirmed.…”