A randomized comparison of cyclophosphamide, adriamycin, and 5‐fluorouracil with triethylenethiophosphoramide and methotrexate, both as sequential and as fixed rotational treatment in patients with advanced ovarian cancer

The combinations of triethylenethiophosphoramide and methotrexate (TM) and cyclophosphamide, Adriamycin (doxorubicin), and 5‐fluorouracil (CAF) were compared, both as sequential and fixed rotational treatments for advanced ovarian cancer, with L‐phenylalanine mustard (L‐PAM). Treatment with CAF produced a higher response rate (25% complete responses plus 31% partial responses) than treatment with L‐PAM (15% complete responses plus 18% partial responses). A fixed rotation of TM and CAF resulted in longer survival (median of 15 months and 75th percentile of 27 months) than sequential treatment with TM initially, followed by CAF upon failure (median of 12 months and 75th percentile of 22 months). The fixed rotation of TM and CAF also increased progression‐free survival (median of 12 months and 75th percentile of 24 months) over that achieved by initial treatment with TM (median of 6 months and 75th percentile of 15 months) or L‐PAM (median of 9 months and 75th percentile of 21 months). Most patients (96%) on the fixed rotation were treated with both TM and CAF. Fewer patients (62%) on the sequential schedule with TM actually received both combination regimens, and even fewer patients (37%) beginning on CAF ever crossed over to TM. Patient age of 50 years or younger was a favorable prognostic factor for response, survival, and time to first treatment failure (progression‐free survival). Disease Stage IIIA or IIIB, surgery including a bilateral salpingooophorectomy plus hysterectomy, and treatment within 6 months of initial diagnosis were favorable predictors for both survival and time to first treatment failure. Ambulatory performance status and well‐differentiated disease were favorable prognostic factors for survival. Patients with unevaluable disease failed later than those with evaluable disease who, in turn, failed later than patients with measurable disease. Copyright © 1985 American Cancer Society