CLINICAL APPLICATION OF ADJUVANT CHEMOTHERAPY (CT) IN ADULT SOFT TISSUE SARCOMAS(STS) FOLLOWING A RADOMIZED STUDY. THE ITALIAN SARCOMA GROUP EXPERIENCE

¹Frustaci S, ¹Berretta M, ²Olmi P, ³Barbieri E, ⁴Ippolito V, ¹Buonadonna A. ⁵De Paoli A, ⁶Apice G, ⁷Comandone A, ⁸Gherlinzoni F, ⁹Picci P. From the Italian Sarcoma Group. Divisions of ¹Medical Oncology and ⁵Radiation Therapy, C.R.O.- Aviano, ²Division of Radiation Therapy, Firenze; ³Division of Radiation Therapy, Bologna; ⁴Division of Orthopedics, Brescia, ⁶Division of Medical Oncology, Istituto Tumori, Napoli, ⁷Division of Medical Oncology, Torino, ⁸Division of Orthopedics, Gorizia, ⁹Istituto Rizzoli, Bologna.

Background: After the conclusion (11/96) of the Italian cooperative randomized study of CT in adult STS and its positive results (ASCO `97, Abs N<sup>o</sup> *1785; ASCO `99, Abs N^o *2108), the participating Institutions, continued to treat patients(pts) with the same modality.

Methodology: The present report deals with the analysis of treatment, compliance, toxicity, dose-intensity, pattern of relapse and survival of pts treated in Italy from different Institutions according to the same guidelines of the randomized protocol. The methodology of data collection will be, therefore, different from the perspective study (spontaneous referral, retrospective analysis of unregistered pts, etc.).

Selection criteria: pts > 18 years, affected by spindle cell, greater than 5 cm, high grade STS of the extremities and girdles:

Treatment: Epirubicin(EPI)60mg/m², day 1 and 2; Ifosfamide(IFO) 9g/m² in 3-5 days; G-CSF 300µg s.c. from day +8 until recovery, was planned every 3 weeks for 5 cycles.

Results: From 11/96, more than 50 pts have already been treated in Italy by the same Institutions which participated in the protocol itself (the treatment arm of the protocol dealt with only 53 pts accrued in a four-year period). The data collection is ongoing and analysis of the above mentioned points will be completely available by September `99. Full data are available up to now only for 30 pts. Compliance: 24/30 pts have completed the 5 programmed cycles (5 stopped treatment for hematological toxicity, 1 other causes); the median administrated doses were: EPI 600mg/m² (range: 443-617), IFO 44,7g/m² (range: 31.7-45.8); the average median dose intensity was 88% of the planned program. Grade 3-4 toxicities were: leucopenia in 12/30, thrombocytopenia in 7/30, anemia in 4/30 pts, respectively. After a median follow up time of 20 months 5 pts have already relapsed (1 locally and 4 at the lung level).

Conclusions: The analysis of the clinical approach and results obtained after the conclusion of a prospective randomized trail is of interest and indicates the impact on the clinical decision obtained by the study itself. Even though, the bias of such a retrospective data collection is self-explanatory, the historical comparison with the study-data are of interest in terms of its reliability and reproducibility. This comparison is in our case even more appropriate since the selection criteria and treatment have been the same. A longer follow-up is needed in order to verify the prognostic significance of such an aggressive approach.