A randomized comparative trial of combined versus alternating therapy with cytostatic drugs and high-dose medroxyprogesteron acetate in advanced breast cancer.

A prospective multicenter trial was conducted in 155 consecutive patients with Stage IV breast cancer randomly allocated to receive either (1) vincristin (V) 1.2 mg/m2 (maximum dose, 2 mg), Adriamycin (A) (doxorubicin) 40 mg/m2, and cyclophosphamide (C) 500 mg/m2, all intravenously on day 1, every 4 weeks, in combination with medroxyprogesteron acetate (MPA) 600 mg orally on days 1 through 14, 500 mg intramuscularly on days 1 through 28, and twice weekly afterwards (combined chemoendocrine approach) or (2) the same combination chemotherapy (VAC) for three cycles alternating with MPA in the above-mentioned dosage during 8 weeks (alternating chemoendocrine approach). Results show an overall response rate of 73% with 26% complete responses in the combined treatment arm, whereas in the alternating arm, an overall response rate of 76% with 20% complete responses was observed. In patients with more than one metastatic site, response rate was higher in the combination treatment, and only in this arm were complete responses observed in these patients. Although the median duration of response was long in both treatment arms (combination, 19 months versus alternating, 21 months), the median overall survival in both groups was not definitely prolonged (22 versus 24 months, respectively). However, results in subsets of patients suggest that the alternating chemoendocrine approach may be better for estrogen receptor (ER)-negative patients, for patients younger than 51 years of age, and for patients with a disease-free interval of 1 year or less. Patients with these parameters probably belong to the same population. It is concluded that combination of chemotherapy and high-dose MPA may be indicated in ER-positive patients when a clinical response is urgently needed. In ER-negative patients, the alternating use of both treatment modalities deserves further investigation.