Exatecan in pretreated adult patients with advanced soft tissue sarcoma: results of a phase II--study of the EORTC Soft Tissue and Bone Sarcoma Group.

No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. Exatecan (DX-8951f) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas, has been reported for topoisomerase I-inhibitors, a study with a new and more potent agent seemed justified. We report on a prospective multicentre phase II study of Exatecan in adult soft tissue sarcomas failing 1 or 2 lines of chemotherapy in advanced phase, performed within the STBSG of EORTC. Thirty-nine patients (16 leiomyosarcomas and 23 other histologies) were included in two independent strata and received a total of 141 cycles (median 2). Median age was 61 years, range 25-76. Exatecan was given as i.v. infusion over 30 min at a dose of 0.5mg/m2 every day for five consecutive days, repeated every 21 days. Seventy-four percentage of cycles could be given without dose or schedule modification. The main toxicity was haematotoxicity with grade 3/4 neutropenia in 49%, grade 3/4 thrombocytopenia in 23%, and grade 3/4 anaemia in 15% of patients, respectively. Non-haematological toxicity consisted mainly of grade 2/3 dyspnoea in 36% of patients and grade 2/3 fatigue in 28%. One treatment-related toxic death due to septic shock was reported. Best overall response was no change with 60% in the leiomyosarcoma group and 53% in the non-leiomysarcoma group, respectively. The 3 months progression-free survival estimates are 56% for leiomysarcomas and 26% for other histologies, respectively. Using a two-step statistical design, the trial was stopped after the first step in both strata, due to lack of activity. In pretreated soft tissue sarcoma patients, Exatecan is well tolerated but does not achieve any objective responses. However, with respect to progression-free survival, Exatecan did show some activity in leiomyosarcomas.