Connective Tissue Oncology Society

2001 CTOS Annual Meeting Posters— Surgery

PHASE I TRIAL OF PREOPERATIVE DOXORUBICIN-BASED CONCURRENT CHEMORADIATION AND SURGICAL RESECTION FOR LOCALIZED, RESECTABLE EXTREMITY AND TRUNK SOFT TISSUE SARCOMAS (STS)
Peter W.T. Pisters, Shreyaskumar R. Patel, Valerae O. Lewis, Kristin L. Weber, Patrick P. Lin, Rex Marco, Alan W. Yasko, Kelly K. Hunt, Barry W. Feig, Jonathan C. Trent II
The University of Texas M. D. Anderson Cancer Center

OBJECTIVE: Doxorubicin is active against soft tissue sarcoma and is a potent radiosensitizer. However, no prior studies have examined continuous infusion doxorubicin combined with concurrent radiation for patients with STS. This phase I trial is designed to define the toxicities of concurrent doxorubicin and external beam radiotherapy (EBRT) followed by surgical resection in order to establish the maximum tolerated dose (MTD) of doxorubicin when combined with standard preoperative EBRT.

METHODS: Patients with localized, resectable grade II or III primary or recurrent STS of the trunk and extremity are eligible. EBRT (2 Gy/fraction, 25 fractions) is provided with continuous infusion doxorubicin (starting dose 10 mg/m2/week, Monday to Thursday, x 5 weeks). Doxorubicin dose escalation is determined by the continuous reassessment method (CRM). 23 patients have been treated. The dose escalation scheme (and number of patients treated) for successive cohorts of patients according to the CRM method has been: 12.5 mg/m2 per week (1 patient), 15.0 mg/m2 per week (3 patients), 17.5 mg/m2 per week (19 patients).

RESULTS: The median tumor size was 9.8 cm (range, 1.8 - 22 cm). Histologies included unclassified sarcoma (8 patients), malignant fibrous histiocytoma (7 patients), liposarcoma (4 patients), and 3 patients with other STS. With 23 of 30 planned patients treated, the MTD by CRM appears to be 17.5 mg/m2 per week; 7 patients remain to be treated for complete assessment. Grade III local cutaneous toxicity (confluent moist desquamation) has been observed in 5 patients treated at the 17.5 mg/m2 per week dose level. Grade III neutropenia was observed in 2 patients treated at the 17.5 mg/m2 dose level; no patients have experienced febrile neutropenia.

CONCLUSION: Concurrent continuous infusion doxorubicin-based chemoradiotherapy appears feasible and safe. The MTD of doxorubicin appears to be 17.5 mg/m2 per week when doxorubicin is administered by continuous infusion over 4 days/week for 5 successive weeks with 50 Gy of preoperative EBRT.