INDUCTION CHEMOTHERAPY OF DIBROMODULCITOL, ADRIAMYCIN(R), VINCRISTINE, TAMOXIFEN, AND HALOTESTIN(R) WITH METHOTREXATE IN METASTATIC BREAST-CANCER - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY (E1181)

Patients who have metastatic breast cancer are seldom curable. Chemoth erapy given by conventional doses and schedules generally produces com plete remissions in 10% to 20% of patients. This study sought to deter mine 1) whether a combination of dibromodulcitol, Adriamycin(R), vincr istine, tamoxifen, Halotestin(R), and methotrexate with leucovorin res cue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive meta static breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m (2) perorally days 1 to 10; Adriamycin(R) 45 mg/m(2) intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin(R) , 20 mg perorally daily; methotrexate, 800 mg/m(2) intravenously days 15 and 22; and leucovorin, 15 mg/m(2) perorally every 6 hours for 9 do ses, starting 4 hours after methotrexate. After induction, patients wh o had stable disease or a partial response were treated with a cycloph osphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patie nts in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off ther apy until relapse, when DAVTHML was to be given again. Fifty-eight pat ients were included in this study. During induction, 26% of eligible p atients experienced a complete remission; overall response rate was 80 %. The median time to treatment failure and the median survival time o f eligible patients was 11.1 and 24.0 months, respectively, This did n ot change significantly when all the patients were included in the eva luation. The 3-year and 5-year survival rates were 37% and 11%, respec tively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytop enia (20%), and vomiting (17%). No lethal toxicity was documented duri ng therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remissio n rates from our study were encouraging. The toxicity of DAVTHML was t olerable, with the exception of myelodysplastic syndrome from dibromod ulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.