RESULTS OF 2 CONSECUTIVE TRIALS OF DOSE-INTENSIVE CHEMOTHERAPY WITH DOXORUBICIN AND IFOSFAMIDE IN PATIENTS WITH SARCOMAS

The authors evaluate the efficacy and feasibility of dose-intensive do xorubicin and ifosfamide combination chemotherapy in patients with sar comas. From January 1995 to April 1996, 33 evaluable patients with eit her metastatic sarcoma or primary sarcomas with a high-risk for metast ases (all except one was previously untreated with chemotherapy) were treated on two consecutive protocols. The median age was 45 years (ran ge, 15-68 years). The first protocol included doxorubicin at 75 mg/m(2 ) given as a 72-hour infusion on days 1 to 3 along with ifosfamide at 2 g/m(2)/d over 2 hours x 5, days 1 to 5 (protocol AI 75/10). Granuloc yte colony-stimulating factor (G-CSF) was used only if indicated accor ding to American Society of Clinical Oncology guidelines. The second p rotocol included doxorubicin at 90 mg/m(2) as a 72-hour continuous inf usion and ifosfamide at 2.5 g/m(2)/d for 4 days (protocol AI 90/10) wi th prophylactic G-CSF. A median of four cycles were administered (rang e, 1-6). Three patients achieved a pathologic complete response (CR) a nd 18 patients achieved a partial response (PR) for a response rate (R R) of 64% (95% confidence interval (CI), 45-80%). Response rate for th e subset of patients with soft-tissue sarcomas was 66% (95% CI, 46-82% ). Only three patients progressed on therapy. Febrile neutropenia was noted in 31% of cycles at Al 75/10 and in 56% of cycles at AI 90/10. O ne patient developed reversible grade 3 central nervous system (CNS) t oxicity. There was one treatment-related death on AI 90/10 secondary t o doxorubicin cardiac toxicity at a cumulative dose of 435 mg/m(2). Do se-intensive doxorubicin plus ifosfamide is feasible in appropriately selected patients and appears to be a very active regimen in patients with sarcomas. The authors are currently testing this regimen with G-C SF and thrombopoietin.