Patients who have metastatic
breast cancer are seldom curable.
Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of
dibromodulcitol,
Adriamycin,
vincristine,
tamoxifen,
Halotestin, and
methotrexate with
leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with
chemotherapy-naive metastatic
breast cancer. Patients were treated with six 28-day cycles of DAVTHML
induction chemotherapy consisting of
dibromodulcitol, 135 mg/m2 perorally days 1 to 10;
Adriamycin 45 mg/m2 intravenously day 1;
vincristine, 2 mg intravenously day 1;
tamoxifen and
Halotestin, 20 mg perorally daily;
methotrexate, 800 mg/m2 intravenously days 15 and 22; and
leucovorin, 15 mg/m2 perorally every 6 hours for 9 doses, starting 4 hours after
methotrexate. After induction, patients who had stable disease or a partial response were treated with a
cyclophosphamide,
methotrexate, and
5-fluorouracil-based regimen (CMF). Patients
in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off
therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median
time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were
leukopenia (75%),
anemia (20%),
thrombocytopenia (20%), and
vomiting (17%). No lethal toxicity was documented during
therapy; however, 1 patient later died of
myelodysplastic syndrome induced by
dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of
myelodysplastic syndrome from
dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.