Phase II trial of gemcitabine in patients with pretreated advanced soft tissue sarcomas

Because of the low number of active cytotoxic drugs and their limited activ ity, the evaluation of new anti-cancer agents for their activity in soft ti ssue sarcomas is a continuing need. The objectives of this prospective phas e II trial of gemcitabine were to estimate the response rate and to define the toxicities of prolonged infusions of low-dose gemcitabine in patients w ith pretreated advanced soft tissue sarcomas, Patients were eligible if the y had a histologic diagnosis of unresectable, recurrent or metastatic, prog ressive soft tissue sarcoma, and if they had been treated with at least one prior chemotherapy consisting of an anthracycline- and/or ifosfamide-conta ining regimen. Gemcitabine was administered as a 360 min infusion on days 1 , 8 and 15 of a 28 day cycle. The initial dose of gemcitabine was 200 mg/m( 2) in all patients. Dose escalation to 250 mg/m(2) was allowed in the case of stable disease and good tolerability of the drug. All 18 patients (media n age 58 years) who enrolled were treated with gemcitabine, and all were as sessable for toxicity, response and survival. Only two of these 18 patients had an objective response to a previous palliative chemotherapy. A median of 3 cycles (range 1-7) of gemcitabicin were administered. Two (11%) of the patients had a partial response lasting 5 and 6 months, respectively. Both of these patients had only lung metastases, Whereas one of these patients had a transient partial response to the foregoing chemotherapy (consisting of ifosfamide and doxorubicin), the other patient has been progressive on t hese drugs. One additional patient, progressive on ifosfamide and doxorubic in, had an objective response of greater than 50% confined to the lungs and stable local recurrence for 6 months. Six patients had stable disease for 3-6 months and nine patients had disease progression. The median survival w as 8 months. Treatment generally was well tolerated with six patients havin g transient grade 3 non-hematologic toxicity, four having grade 3 neutropen ia, and one having grade 4 neutropenia and thrombocytopenia. Gemcitabine, g iven as a prolonged infusion at a low dose level, has a favorable toxicity profile and displays antitumor activity in patients with intensively pretre ated, advanced soft tissue sarcomas. [(C) 2000 Lippincott Williams & Wilkin s.].