Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. Cancer and Leukemia Group B.

Abstract

Three combination chemotherapy regimens each with or without the methanol-extracted residue of bacillus Calmette-Guérin (BCG) (MER) were compared for efficacy. After stratification for disease-free interval and dominant sites of disease, patients were randomized to either CMF (cyclophosphamide [CYC], 100 mg/m2 orally, days 1 through 14; methotrexate [MTX], 40 mg intravenously [IV], days 1 and 8; 5-fluorouracil [5-FU], 500 mg/m2 IV, days 1 and 8), or CAF (CYC, 100 mg/m2 orally, days 1 through 14; doxorubicin [DOX], 25 mg/m2 IV, days 1 and 8; 5-FU, 500 mg/m2 IV, days 1 and 8), or CAFVP (CAF as above plus vincristine [VCR], 1.0 mg/m2 IV, days 1 and 8; and prednisone [PRED], 40 mg/m2 orally, days 1 through 14). Nonspecific immunotherapy with MER was administered in five sites at 100 micrograms or at the lowest tenfold dilution that produced a 1-cm indurated lesion. A total of 432 patients were entered, but 37 were disqualified, leaving 395 evaluable for treatment results and toxicities. One hundred thirty-five evaluable patients were randomized to chemoimmunotherapy until October 28, 1978. One hundred twenty-six evaluable patients were randomized to chemotherapy alone in the same time period. For the entire study, a total of 260 evaluable patients were randomized to chemotherapy. Chemoimmunotherapy patients were compared with the initial 126 chemotherapy patients. Chemotherapy regimens were compared among all 260 patients. Patient characteristics were similar between regimens and between chemotherapy and chemoimmunotherapy treatment groups. For patients on chemotherapy plus MER, there was no significant differences between the regimens for response frequencies: 43%, 41%, and 32%, respectively for CMF, CAF, and CAFVP. The comparable chemotherapy alone group had 36%, 58%, and 63% response, respectively. The response rates, adjusted for chemotherapy regimen, were 52% and 38% (P = .02) for chemotherapy and chemoimmunotherapy, respectively. MER was associated with painful ulcers and fevers. Thus, MER produced toxicity without response or survival benefit and further randomization after October 28, 1978 was to chemotherapy alone. For 260 evaluable patients on chemotherapy alone, the complete (CR) and partial responses (PR) were 37%, 55%, and 58%, respectively for CMF, CAF, and CAFVP. These response rates for CAF and CAFVP were significantly better than CMF (P = .01 and P less than .01, respectively). These comparisons were consistent within subgroupings such as dominant sites of disease.(ABSTRACT TRUNCATED AT 400 WORDS)

A randomised comparative trial of mitozantrone/methotrexate/mitomycin C (MMM) and cyclophosphamide/methotrexate/5 FU (CMF) in the treatment of advanced breast cancer

“…The overall response rates and survival for both arms of this trial were similar to those reported in large series using both CMF and Adriamycin-containing regimens (Coates et al, 1987;Cummings et al, 1985;Hayes & Henderson, 1987;Macaulay & Smith, 1986;Smalley et al, 1983). Occasionally, better results have been reported, particularly with Adriamycincontaining regimens (Aisner et al, 1987), but these have not been confirmed by other studies. Comparisons of results between different trials are difficult because of potential variations in the selection criteria used for patient entry.…”

“…It must be noted that the doses of our CMF combination were lower than those reported in some other studies (Cummings et al, 1985;Aisner et al, 1987;Coates et al, 1987), but not all: the dose rate was in fact slightly higher than the higher of two dose levels of CMF compared in a recent trial (Tannock et al, 1988). In addition treatment actually delivered is often less than treatment planned: in a classic adjuvant CMF trial only 17% of patients received the intended dose (Bonadonna et al, 1981).…”

“…Combination chemotherapy for metastatic breast cancer commonly achieves tumour response rates of 50-60% in large series (Aisner et al, 1987;Brambilla et al, 1976;Coates et al, 1987;Cummings et al, 1985;Tormey et al, 1982;Hayes & Henderson, 1987) but long term remissions are rare and one of the main aims of treatment is symptom palliation. It is therefore important to develop regimens that are not merely effective, but have low subjective toxicity.…”

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

“…The most commonly used doxorubicin-based combinations are AC (doxorubicin, cyclophosphamide), and FAC (5-fluorouracil, doxorubicin, cyclophosphamide) [8]. Several randomized clinical trials showed higher RR and improvements in disease-free survival for patients treated with FAC compared to CMF [9][10][11][12][13][14]. Other studies showed equivalence between these regimens.…”

Randomized trial comparing cyclophosphamide, methotrexate, and 5–fluorouracil (CMF) with rotational CMF, epirubicin and vincristine as primary chemotherapy in operable breast carcinoma

“…1,2 Primary chemotherapy can also be used as a model for comparing the activity of different drugs or combinations. It has been reported that anthracycline containing regimens are superior to cyclophosphamide, methotrexate, 5-fluorouracil (CMF) in advanced disease in terms of response rates and, less consistently, survival, [3][4][5][6][7] furthermore, when given in the adjuvant setting, those regimens have also been shown to reduce the risk of recurrence and death. 8 However, to the best of our knowledge, there is no information in the literature concerning the relative merits of CMF versus anthracycline containing combinations as primary treatments.…”