Five-drug therapy in advanced breast cancer. Factors Influencing Toxicity and Response

Abstract

Seventy‐four women with advanced breast cancer were treated with a combination of continuous oral prednisone (45 mg/day × 2 wks, 30 mg/day × 2 wks, then 15 mg/day) and cyclophosphamide (100 mg/day), and weekly injections of 5‐fluorouracil, 500 mg; methotrexate, 25 mg; and vincristine, 1 mg. Thirtyone of 74 showed an objective response to therapy for a median length of 5 months. The responses were seen in soft tissue and visceral metastases. Definite recalcification of lytic bone lesions was seen in only 1 patient. Prior therapy decreased the number of responses to five‐drug therapy. With no prior cytotoxic therapy, 11/16 responded; with prior 5‐FU therapy 13/25 responded; with both prior 5‐FU and alkylating agent therapy, 7/33 responded. The median length of response was similar regardless of prior therapy. Toxicity was moderately severe; dosage modifications were necessary in the majority of patients, and there were seven drug contributory deaths during therapy. After failure of this combination, only 5/28 responded briefly to a variety of therapeutic measures. Comparable survival from first recurrence was seen whether response or failure occurred on five‐drug therapy. Trials of sequential vs. combination therapy will be necessary to define the role of combination therapy in advanced breast cancer.

Combination chemotherapy and adriamycin in patients with advanced breast cancer.A Southwest Oncology Group study

“…T h e best results for remission induction, 59%, were obtained with the weekly combination. This is similar to the 69% (11/16) antl 67% (6/9) rates of responses already reported in patients without prior chemotherapy.4316 T h e median duration of our responses, 250 days, compares well with the median of 150 days reported by Davis et al 4 'I'he results with the intermittent five-drug combination are disappointing. Once obtithed, the responses lasted a median oE 310 SWOG now has experience with adriamycin as a single agent in 315 patients with breast cancer.]'…”

Quadruple chemotherapy for advanced malignant disease

“…The validity of this approach has been demonstrated in animals and in humans with childhood and adult acute leukaemia (Freireich et al, 1964;Thompson et al, 1965) and metastatic cancer of the testis (Li et al, 1959(Li et al, , 1960. Combination chemotherapy has now been applied to a wide variety of advanced malignant disease and the initial reports have been encouraging (Costanzi and Coltman, 1969;Price and Goldie, 1971 ;Priestman and Hanham, 1972), particularly in regard to breast cancer (Deemarsky and Chernomordikova, 1970;Livingstone and Carter, 1970;Hanham et al, 1971;Shingleton et al, 1971;Davis et al, 1974;Brunner et al, 1975).…”