856 Intensified adjuvant chemotherapy for extremity soft tissue sarcomas (STS)

Abstract

Adjuvant chemotherapy for STS still remains a matter of debate, since just few randomized studies have indicated a small advantage in terms of disease free interval or overall survival at preliminary reports. However, the majority of those trials have not included adequate doses of anthracyclines nor the today most active agent Ifosfamide (IFO). To re-evaluate the role of adjuvant chemotherapy in extremity STS, we started in June ‘92, a co-operative randomized prospective adjuvant study comparing a control arm to an intensified chemotherapy arm. Treatment consisted of Epirubicin 60 mg/m2, day 1&2, Ifosfamide 1.8 g/m2 × 5days as 1 hr infusion, MESNA 60% of the daily IFO dose fractionated in 3 separated doses, fluids 1.5–2.0 litres/day and G–CSF 300 μg/day from + 8 to + 15; treatment was scheduled every 3 weeks for a total of 5 cycles. Of the 37 up to now randomized pts to the chemotherapy arm, 25 are evaluable (5 cycles completed + two months follow-up) for the toxicity and dose intensity evaluation purpose (12 pts not yet evaluable). The median nadir of WBC and PLTS was 1300/μ1 (range: 200–8000/μ1); and, 120000/μ1 (range: 10000–250000/μ1), respectively. Overall, a G4 leukopenia and thrombocytopenia was noted in 30% and 5% of cycles respectively. Anemia progressively worsened and the median HB fall from basal values to the nadir of the 5th cycle was of 4 g/dl (range 0–9.8 g/dl); in 12 of 25 pts (48%) PRBC transfusions were given to prevent symptoms from anemia. Nevertheless, an optimal recovery to pre-treatment values was obtained after 2 months from end of treatment (median HB 13.5; range: 12.7–14.8). Neutropenic fever was observed in 15% of the cycles, prophylactic antibiotics were administered in further 3% of cycles. No pts received pits support. The median average received dose intensity (ARDI) was of 91% (range: 67–100%) and 19/25 pts (76%) received an ARDI > 80%. Causes of reduction in dose intensity were delay in retreatment in 24 cycles and reduction of the dose in 40 cycles. Even through the toxicity was substantial (anemia and leukopenia) it was possible to give an adequate dose intensity to the majority of pts. All but one pt (3 cycles received) completed the forseen 5 cycles employing the predefined dose reduction schema.