Previous in vitro and in vivo studies showed a synergistic effect of concomitant doxorubicin and radiotherapy in a variety of solid tumors. From 1988 to 2000, we have investigated in a pilot study and then in a phase II study the efficacy of a concomitant doxorubicin radiotherapy treatment in patients with advanced and/or metastatic soft tissue sarcomas (STS). We enrolled and treated a group of 115 patients with advanced STS, with metastases (61%), frequently pretreated (59%), predominantly G2/G3 (84%). Doxorubicin was administered by continuous infusion at a dose of 12 mg/m2/day over 5 consecutive days concomitantly with radiotherapy; treatment was given on ambulatory basis at 2-week intervals with support of granulocytes colony stimulating factors (GCSF). In the whole group of 115 patients a clinical objective response (ORs) rate of 67% was obtained, with 11% complete and 56% partial responses. No patient progressed while on therapy, except one who progressed in non-irradiated metastatic tumor. Treatment (median 3 cycles) was well tolerated with no WHO grade 3 toxicity (apart from alopecia) and no acute or chronic cardiotoxicity. Thirty-nine responder patients underwent surgery (24 primary tumors, 10 relapses, 5 relapses plus isolated lung metastases). The median survival time(s) was 29 months in the whole series and over 50 months in responder patients. A multivariate analysis showed a positive association between survival and sex (HR=1.8; CI 95%, 1.0-3.4), performance status (HR=2.1; CI 95%, 1.1-4.0), ORs (HR=7.9; CI 95%, 3.5-18.1) and surgery (HR=8.8; CI 95%, 2.1-35.9). Low toxicity, high OR rate and positive survival time trend make the concomitant chemo-radiotherapy an efficacious approach for advanced STS.

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