Combination versus sequential single agent chemotherapy in advanced breast cancer: associations with metastatic sites and long-term survival

Abstract

Summary Two hundred and twenty-two patients with advanced breast cancer were randomised in two separate trials of similar design to either concomitant combination treatment or sequential use of the same drugs given as single agents changed only at disease progression. Both trials used cyclophosphamide, methotrexate, 5-fluorouracil and prednisone; the WCSG using triiodothyronine and the SECSG using vincristine as the remaining agent. A common data base was generated for these trials and combined for analysis. Considering all patients, combination treatment was associated with a significantly increased response (46 versus 25%, P<0.05) but not survival improvement. For the 141 patients without liver involvement, survival was closely comparable in both treatment arms. Combination therapy did result in significant survival benefit for patients with liver involvement (P<0.05). These studies demonstrate: (1) in the majority of breast cancer patients, sequential single agent therapy can result in survival comparable to combination treatment; and (2) sole consideration of response frequency does not represent the optimal criterion to compare therapeutic approaches in advanced breast cancer.

Prognostic Subgroups: The Key Factor for Treatment Outcome in Metastatic Breast Cancer

“…One expects a lower CR rate from patients receiving monotherapy and therefore by analyzing the collective survival data one can see if achieving a CR is related to a prolonged survival. Chlebowski et al [16] did such a study. Advanced breast cancer patients (n = 222) were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone cither sequentially as single agents or as a complete schema.…”

Chemotherapy of Metastatic Breast Cancer: What to Expect in 2001 and Beyond

“…However, it is not clear that polychemotherapy regimens result in improved survival when compared to the same agents administered sequentially. Chlebowski et al [69] randomized 222 women with metastatic breast cancer to CMFP ± V versus sequential single-agent therapy. In this study there was no difference in overall survival among both groups; RR was higher in the combination arm, particularly for patients with liver metastases, and combination chemotherapy was associated with greater toxicity.…”

First-Line Monochemotherapy with Mitoxantroneversus Combination with Fluorouracil, Epirubicin and Cyclophosphamide in High-Risk Metastatic Breast Cancer: A Prospective Randomized Multicenter Clinical Trial

“…However, Carmo-Pereira [11] using fluorouracil, Canellos [12] using phenylalanin mustard, and Mouridsen [13] using cyclophosphamide as monotherapy got better OAS in the combination treatment. Chlebowski et al [14,15] using a sequence of cyclophosphamide, then fluorouracil, then methotrexate, then prednisolone found increased survival times in patients with liver involvement when receiving combination chemotherapy up-front. These studies, however, are probably not representative for decisions nowadays because of completely different diagnostic possibilities and thus different times from first diagnosis of metastases until death.…”