Impact on Progression-Free Survival of Adjuvant Cyclophosphamide, Vincristine, Doxorubicin (Adriamycin), and Dacarbazine (CYVADIC) Chemotherapy for Stage I Uterine Sarcoma

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Abstract
To assess the impact on progression-free survival of the use of the multiagent chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dacarbazine (CYVADIC) as adjuvant treatment for patients with stage I uterine sarcoma: 20 evaluable patients who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for stage I uterine sarcoma received adjuvant multiagent chemotherapy with vincristine sulfate 1 mg/m2 days 1 and 4, doxorubicin (Adriamycin) 40 mg/m2 and cyclophosphamide 400 mg/m2 day 2, and dacarbazine 200 mg/m2 days 1 through 4 for a total of 9 monthly cycles or until recurrence of disease was documented. Patients were followed for a median of 65 months (range: 5-116 months). Myelotoxicity was monitored by weekly complete blood counts, cardiac toxicity by monthly radionuclide angiography, and neurotoxicity by monthly physical examination. Survival and progression-free survival were calculated by the method of Kaplan and Meier (17). The Fisher exact test was employed to determine the significance of recurrence rates between histologic groups (18). These 20 patients received 172 of a planned 180 cycles of chemotherapy. Dose reductions in response to myelotoxicity were necessitated in four cycles among three patients. Mild neurotoxicity was observed in six patients (30%) and moderate neurotoxicity in one patient (5%). A decrease in cardiac ejection fraction of > 10% was observed in two patients (10%). No deaths ascribable to complications arising from chemotherapy were observed. Seven patients (35%) developed recurrence of disease. Recurrence rates for pure sarcomas and mixed mesodermal tumors did not differ significantly (P = .65). Progression-free survival for the population at 2 years was 80% and at 5 years was 65%. This study describes the largest prospective trial of adjuvant combination chemotherapy for patients with stage I uterine sarcoma reported to date. Adjuvant chemotherapy employing the combination of cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dacarbazine (CYVADIC) failed to impact significantly on long-term survival in this group of patients with stage I uterine sarcoma.

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