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Background: High cure rates are expected in good-risk metastatic nonseminomatous germ-cell tumor (NSGCT) patients with bleomycin, etoposide and cisplatin. Patients and methods: Patients received either three cycles of BE500P or four cycles of E500P every 3 weeks. Disease was defined according to the Institut Gustave Roussy prognostic model. Patients were retrospectively assigned into the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. A sample size of 250 patients was necessary for an expected favorable response rate (primary end point) of 90% and not more than a 10% difference between the two arms. Results: Among 257 assessable patients, 124 and 122 patients achieved a favorable response in the 3BE500P and 4E500P arms, respectively (P = 0.34). Median follow-up was 53 months. The 4-year event-free survival rates were 91% and 86%, respectively (P = 0.135). The 4-year overall survival rates were not significantly different [five deaths versus 12 deaths, respectively (P = 0.096)]. Similar nonsignificant trends were observed in good IGCCCG prognosis patients. Conclusions: Both regimens produced similar results in terms of favorable response rates. As the trial was underpowered for survival analyses, conclusive data would require a larger randomized trial. Unless such a study is done, 3BE500P is the treatment of choice for metastatic NSGCT patients.

10525 Background: Trabectedin (ET-743, Yondelis), a marine-derived alkaloid has demonstrated significant activity in the treatment of soft tissue sarcomas (STS) in phase III trials, and has recently received EMEA approval in this indication. A subtype that accounts for 10% of STS, MRCL, displays the fusion FUS-CHOP in 95% of all cases. Preliminary results of neoadjuvant trabectedin (T) in advanced MRCL show reduction in the radiological density of the tumor, clinical improvement, and a pathological complete response (pCR) in the resected tumor mass. A phase II study to further determine the response to T in the MRCL population is presented. Methods: In this multicenter Phase II trial, patients (pts) with locally advanced (stage III) or locally recurrent MRCL were treated for 3 - 6 cycles with T (1.5 mg/m2 q3wk) in the neoadjuvant setting. Main endpoints were: pCR rate, objective response rate by RECIST, and correlation of molecular parameters from tissue samples with clinical outcomes. Results: Twenty-five pts with locally advanced MRCL have been recruited, of whom 20 are evaluable. All had the translocation (t12q13, 16p11) which causes the chimeric FUS-CHOP. Median age was 53 (23–75) and male:female ratio was 1. Thirteen pts completed therapy and underwent curative surgery. Pathological assessment was performed in 10 pts: 2 achieved pCR, 1 as per central pathology review and 1 by local pathology assessment. In addition, 1 pt had a very good pathological response. Ten patients remain to be histologically evaluated. Response rate by RECIST from pts who completed therapy was: 6 partial responses (46%) and 7 disease stabilizations. Remarkably, pathological response does not entirely correlate with response by RECIST since the pts with pCR still had radiological disease but no malignant component was found in the excised tumor mass (only connective and reactive tissue). Two serious adverse reactions of severe rhabdomyolysis, and asthenia, nausea and transaminase elevation were reported. Most common toxicities were liver enzyme elevation, neutropenia and thrombocytopenia. Conclusions: These preliminary results in terms of objective and complete pathologic responses, strongly suggest that T may have a role in the neoadjuvant setting in pts with MRCL. [Table: see text]

10507 Background: Masitinib mesylate (AB1010, AB Science, Paris, France) is a novel protein tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib mesylate against bith wild-type c-Kit receptor and its mutated form in the juxtamembrane region. Masatinib also inhibits PDGFR and FGFR3. This multicenter phase II study evaluated the efficacy and safety of masatinib as a first-line treatment of advanced GIST. Methods: Imatinib-naïve patients with inoperable, locally advanced or metastatic GIST received oral masatinib (7.5 mg/kg/day) until progression, refusal or toxicity. A Simon “minimax two stage” design was used. Efficacy variables included response rate at two months, best response according to RECIST, disease control rate (DCR), metabolic response rate and progression free survival (PFS). Results: 30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. The most frequent relevant grade 3 toxicities were rash (10%), neutropenia (7%) and abdominal pain (7%). One patient presented a grade 4 skin exfoliation. Three patients discontinued treatment due to suspected toxicity. At two months, the response rate was 20% (6/30 patients) according to RECIST (DCR of 98.7%, 29/30 patients) and 84.6% (11/13 evaluable patients) according to FDG-PET response criteria. After a median follow-up of 23.7 months, there were 6.7% of CR, 43.3% of PR, 46.7% of SD and 3.3% of PD as best response (DCR of 96.7%). Mean time to response was 5.7 months (0.8 to 23.3 months). The median PFS was 27.2 months with PFS rates of 68.8% at 1 year and 60.2% at 2 years. Up to date, all but one patient are alive (one patient died of post-surgical complications, unrelated to treatment). Mutational analyses of the patients’tumors are ongoing. Conclusions: The results observed with masatinib compare favorably with those reported with imatinib in front-line treatment of advanced GIST both in term of safety and efficacy and support the initiation of a phase III randomized clinical trial. [Table: see text]

From January 1988 to January 1992, 141 patients entered the EW88 protocol based on the chemotherapy (CT) used in St. Jude Hospital since 1978 (JCO 7, 208–213, 1989). Among them, 44 were young adults (15 to 35 yrs, median 20 yrs). Induction CT consisted in Cytoxan 150 mg/m2 p.o. × 7 days followed by Adriamycin 35 mg/m2 IV on day 8 for 5 courses beginning days 1, 15, 29, 50 and 71. Surgery was recommended whenever possible. Radiation was based upon the quality of surgery and the histological response to CT. Maintenance CT was based on vincristine + actinomycin and cytoxan + adriamycin. Total duration of therapy was 10 months. In March 1995, median follow-up of the cohort was 64 months (38–87 m). Outcome was similar in adults and children. 97 pts 44 pts ≥ 15 yrs no. pts without initial control 0 4 no. pts with local relapse 21 8 no. pts with isolated metastases 17 12 5year DFS 58% (± 10) 52% (± 15) N.S. 5 year Survival 64% (± 10) 65% (± 15) N.S.

From 1982 to 1992,146 adults with Ewing's sarcoma, have been treated for their first tumoral event in 3 french cancer centres. There were 91 maies and 56 females. The median âge was 20.2 (16–55) years. As regards site, 62 pts (42.5%) had extremity lesions, 57 pts (39%) had axial tumor (vertebra 8%, pelvic 31%), 13 pts (9%) had rib primary lesion, and 14 pts (9.5%) had extraskeletal disease. 41 pts (28%) were metastatic at diagnosis. Chemotherapy was the first treatment in 90% of the no metastatic patients and 88% of the metastatic patients were treated with curative intent. All patients could receive more than 90% of the previous dose of chemotherapy, although 53 pts received a regimen initially designed also for pediatrie pts. In 66 pts (45%) surgery was done as part of local treatment, of those 45 pts were given post operative radiotherapy. Radiotherapy was performed in 119 pts with a median dose of 45 Gy; 23% of the patients received less than 50 Gy. With a median follow-up of 5 years, overall survival (OS), metastatic free survival (MFS) and local recurrence free survival (LRFS) were and for the no metastatic and the metastatic pts: 50.3%/7% (P OS DFS MFS LRFS Histologie responso 36.5/85.5 30.4/43.4 36.2/52.8 0, 1,2/3,4 p = 0.003 p = 0.02 p = 0.03 xm 44.6/65.3 37.5/44.8 40.4/53.7 p = 0.04 Sites extremity 61.3 p = 0.05 47.4 p = 0.02 47.97 p = 0.06 74.3 pelvic 38.2 28.3 33.1 52.6 vertebra 0 p 0 p 40 0 central 26.2 17.4 39.9 56.4 chest 85.7 51.4 68.6 80 extraskeletal 88.9 62.2 62.2 89.9 Prognostics factors correlated with a poor overall survival were female gender, axial tumor localization and poor histologie response to initial chemotherapy. In conclusion, from this series, naturai history and evolution did not show out to be different for Ewing sarcoma occurring in children. Moreover pediatrie chemotherapy protocols appeared to be correctly tolerated. As in pediatrie pts, novel approached had to be designed for M+ and poor responders to initial chemotherapy.

This report describes the clinical and pathological features and evolution of 2 cases of locally advanced undifferentiated liposarcoma. In each case, a tumor differentiation was noted after induction chemotherapy, which otherwise determined in both patient a dramatic tumor response. This may be explained by heterogenicity of the primary tumors, which may include several cell contingents with different responses to chemotherapy. This constitutes a potential impediment to the efficacy of induction or adjuvant chemotherapy.