e21519 Background: Dacarbazine (DTIC) is the standard treatment for metastatic soft tissue sarcoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine but potential for resistance exist. Metronomic administration of TMZ might be a way to overcome resistance. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Methods: We reviewed data of metastatic soft tissue sarcoma patients treated at our Institutions with cisplatin (25 mg/m2 every 7 days for 3 out of 4 weeks) plus TMZ (50 mg/m2/day from day 2 for 27days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC. Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18–74); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases and grade 2 in 10 cases, respectively. Other toxicities included thrombocytopenia (1 case grade 3 and 2 cases grade 2), anemia (1 grade 3 and 2 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 9 patients had a partial response (27.3%; 95% exact CI: 7.0–35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19–57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI: 16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr). Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic soft tissue sarcoma are encouraging, in light of the negative prognostic features of treated patients.