gms | German Medical Science

Background: To determine whether dose-intensive neoadjuvant chemotherapy is a feasible and effective approach in patients (pts) with unresectable soft tissue sarcoma (STS).

Patients and methods: Treatment consisted of 3 cycles of adriamycin (75 mg/sqm) on day 1 and ifosfamide 12 g/m2 as 72h continuous infusion (AI) followed by one cycle of high-dose chemotherapy (HD-ICE), etoposide 500 mg/sqm, carboplatin 500 mg/sqm and ifosfamide 4 g/m2, applied on day –4 through -2, and retransfusion of PBSC on day 0. Presence of distant metastases deemed resectable was allowed.

Results: Between 11/97-2/00 and 4/01-6/04 20 pts, median age 45 (21-62) years, with high grade STS and different locations (retroperitoneum, trunk, extremity) have entered into this prospective trial, either with primary locally advanced STS at primary diagnosis (65%) or with local recurrences (35%). Four pts had additional single resectable metastases in the lung (3) or the liver (1). Fifteen pts (79%) have completed all 3 planned AI cycles and attained a disease stabilisation/minor (47%) or partial remission (32%); one pt is still ongoing. The other 4 pts revealed disease progression after the first (n=1) or second AI cycle (n=3). Two pts did not receive HD-ICE because of ineffective apharesis and grade III neurotoxicity. HD-VIC was well tolerated without dose reduction in the remaining 10 pts (2 pts still ongoing). Non-haematological grade III toxicity consisted of emesis in 2 pts (22%), and mucositis as well as neurotoxicity in one pt each (11%). After PSCT leucocytes and thrombocytes counts recovered on day 10 and 12, respectively. Tumor assessment revealed one additional PR following HD-ICE. After completion of AI+HD-ICE 3 pts without significant tumor shrinkage underwent preoperative radiation according to protocol. In total, 11 of 17 currently evaluable pts (65%) were allocated to surgery. R0 resection was performed in 9 of 11 pts (82%). In one pt a lung metastasis has been removed simultaneously. After a median follow up time of 18+ mos (range, 4-72+) the 1-yr PFS rate is 26% and the 1-yr survival rate 76%. Depending on the resection status median survival is 38 or 18 mos (p<0.01).

Conclusion: Neoadjuvant AI plus HD-ICE with autologous PSCT is a feasible regimen with an acceptable toxicity profile in pts with locally advanced STS. R0 resection as the primary end point was realised in 65% of the pts.