Objective: The objective of this multicenter phase III trial was to study the impact on time to treatment failure (TTF) and survival of cyclophosphamide, Adriamycin, and 5-fluorouracil (CAF) versus CAF/thiotepa, Adriamycin, vinblastine, and Halotestin (TsAVbH), a partially noncross-resistant regimen used in a rotating schedule in the treatment of hormone insensitive metastatic breast cancer in accordance with the Goldie and Coldman hypothesis.
Methods: Three hundred forty-three patients received 6 cycles of induction treatment with one of 2 regimens. Patients with estrogen receptor-negative tumors or those with estrogen receptor-positive or estrogen receptor-unknown tumors with demonstrated unresponsiveness to hormone treatment were eligible. Complete responders were randomized to either observation or maintenance therapy with cyclophosphamide, methotrexate, 5-fluorouracil, prednisone, tamoxifen, and Halotestin (CMF[P]TH). Patients with partial response or stable disease on completion of induction therapy were maintained on CMF plus Halotestin.
Results: There were no differences in the primary end point of TTF (median 7.3 and 7.4 months, respectively). There was a significant difference in TTF and survival by duration of disease-free interval: a median of 8.8 and 21.2 months for those with a disease-free interval of > or =2 years versus 6 to 8 and 13.3 months for those with a disease-free interval <2 years (P = 0.016 and <0.001), respectively. Toxicity of the 2 treatment regimens was similar.
Conclusion: There were no differences observed in TTF, survival, and toxicities between the 2 treatment arms, both of which contained doxorubicin (Adriamycin) as the most active agent. The results of observation versus maintenance in complete responders were reported separately.