Phase I/II study of docetaxel, ifosfamide, and doxorubicin in advanced, recurrent, or metastatic soft tissue sarcoma (STS)

Summary Background: Based on reports of the efficacy of docetaxel (T) in STS, we undertook a phase I/II trial to determine the response rate (RR), dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of addition of T to doxorubicin (A) and ifosfamide (I) in advanced STS. Methods: Patients with advanced, recurrent, or metastatic STS, without prior chemotherapy, were enrolled in a dose escalation trial. Dose levels: I-A 40 mg/m²; I 4.0 gm/m²; T 40 mg/m², II-A 50; I 5.0; T 50, III-A 60; I 6.0; T 60, and IV-A 75; I 7.5; T 75. MTD was defined as the dose producing DLTs in ≥2 of 3–6 patients treated. Results: 21 patients were accrued. Median age: 55 (28–78) years. Histology: leiomyosarcoma 10, spindle cell sarcoma 3, synovial sarcoma 2, angiosarcoma 1, fibrous histiocytoma 1, epitheliod hemangio-endothelioma 1, and 3 not specified. MTD was level III (A 60, I 6.0, and T 60). DLT was myelosuppression. All grade 4 toxicities were hematologic. Patients received median 2 cycles (range 2–9). Eight patients (38%) achieved partial response (PR). PR occurred after six cycles in 5 patients. 18 patients died. Median overall survival: 17 months (95% CI, 9.1–33.6 months). Conclusions: The recommended Phase II dose of this combination is level III: A 60 mg/m², I 6.0 g/m², T 60 mg/m², with mesna and granulocyte-colony stimulating factor. The RR is similar to that of AI in other trials, but the survival is better than anticipated.