Concurrent ifosfamide-based chemotherapy and irradiation analysis of treatment-related toxicity in 43 patients with sarcoma

BACKGROUND. The current study was performed to evaluate the toxicity profile of therapeutic doses of ifosfamide (IFX) given concurrently with full-dose external beam radiotherapy (EBRT) in patients with soft tissue and bone sarcomas. METHODS. The medical records of 43 consecutive patients with soft tissue or bone sarcomas who were treated with concurrent IFX and EBRT were reviewed. RESULTS. The median patient age was 20 years. Histologies were rhabdomyosarcoma (n=16 patients), Ewing sarcoma (n=10 patients), malignant fibrous histiocytoma (n=9 patients), and other soft tissue sarcomas (n=8 patients). Thirty-one patients (72%) had localized disease, and 12 patients (28%) had synchronous local and distant disease. Treatment consisted of EBRT (median dose, 50.4 gray [Gy]) with concomitant IFX (median dose per cycle, 10.2 g/m²). All patients with Ewing sarcoma or rhabdomyosarcoma received additional concurrent chemotherapy. Twenty-six patients (60%) received two or more cycles of IFX, and 17 patients (40%) were treated with one cycle of IFX and EBRT. The incidences of World Health Organization Grade 3 and Grade 4 toxicities were 29% (21 of 73 cycles) and 22% (16 of 73 cycles), respectively. Grade 4 systemic toxicities included leukopenia (n=14 patients), neurotoxicity (suicidal ideation; n=1 patient), and diarrhea (n=1 patient). Confluent moist desquamation (Grade 3) occurred in nine patients in the treatment field; no patient experienced Grade 4 local toxicity. Among 14 patients who were treated preoperatively, 2 patients (14%) had a pathologic complete response, and 6 patients (43%) had a pathologic near-complete response (≥90% necrosis). CONCLUSIONS. Local and systemic toxicities after the administration of therapeutic doses of IFX with concomitant EBRT appear comparable to those observed with either treatment alone. These results support the design of prospective studies evaluating concurrent ifosfamide and radiation therapy for patients with sarcomas.