In this phase II trial, 105 eligible patients with no prior chemotherapy and 
advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with 
mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, and 
900 mg/m2 divided over 72 hours by continuous infusion, respectively. Mesna was 
given for 84 to 96 hours at 2,500 mg/m2/d. Myelosuppression was dose limiting, 
causing the only toxic death (sepsis). Nonhematologic toxicity consisted 
predominantly of anorexia and vomiting. Severe mucositis, macroscopic hematuria, 
renal tubular acidosis, renal failure, and CNS toxicity occurred in less than 5% 
of cycles. No cardiotoxicity was detected. The overall response rate (10% 
complete response [CR]) was 47% (95% confidence intervals, 5% to 18% and 37% to 
57%, respectively). Most responses (approximately 70%) were observed within two 
cycles. Median times to progression were 10 and 9 months, respectively. 
Histologic high tumor grade, lesions less than 5 cm, and less than 1 year from 
diagnosis to study entry correlated with the probability of response. The median 
survival was 16 months. Time from diagnosis to study entry, performance status, 
and extent of disease, but not histologic grade, correlated with survival. 
Following CR, two patients remain disease-free at 32 and 16 months. Of the 15 
additional patients rendered disease-free with surgery, two remain disease-free 
at 30 and 18 months with no further therapy. While most relapses occurred in 
sites of prior involvement, death from CNS metastases occurred in 11 of the 80 
patients with high-grade sarcomas, of whom seven were still responding 
systematically (three complete responders). Because of its substantial response 
in this phase II trial, the MAID regimen is being compared with doxorubicin and 
DTIC alone in advanced sarcomas and to observation in the adjuvant treatment of 
high-grade sarcomas in randomized trials.