Caffeine-potentiated chemotherapy and conservative surgery for high-grade soft-tissue sarcoma

Abstract

We report here the results of preoperative and postoperative caffeine-potentiated chemotherapy and limb-sparing surgery for soft-tissue sarcomas. Thirty-six patients with histologically high-grade soft-tissue sarcomas were treated with caffeine-potentiated chemotherapy and conservative surgery (25 cases of limb-sparing surgery and 11 of local tumor excision). There were 13 patients with malignant fibrous histiocytoma (MFH), eight with synovial sarcoma, five with liposarcoma, four with malignant schwannoma, four with epithelioid sarcoma, one with leiomyosarcoma and one with extraskeletal chondrosarcoma. Nine patients were at stage III with lung metastasis and the other 27 at stage IIB without metastasis; 22 were male and 14 female with a mean age of 48 years, ranging from 16 to 77. For intra-arterial preoperative chemotherapy, we administered 2-5 courses of cisplatin (120 mg/m2), doxorubicin (30 mg/m2 x 2 days), and caffeine (1.5 g/m2 x 3 days) to 18 patients, and cisplatin and caffeine to the other 18. Although 15 patients had already undergone unplanned tumor excision at other hospitals before preoperative chemotherapy, all patients underwent definitive limb-sparing surgery after the preoperative chemotherapy. Surgical margins were wide for 28 patients, marginal for three and intralesional for five. Local tumor recurrence was seen in one patient with MFH and one with epithelioid sarcoma. Of the 27 stage IIB patients, lung metastasis newly developed in one with MFH, three with synovial sarcoma, two with malignant schwannoma and one with leiomyosarcoma. As for the effects of preoperative chemotherapy in the 33 eligible cases, radiographically confirmed complete response was seen in two patients, partial response in 20 and no response in 11. Histological response to this preoperative chemotherapy consisted of grade I (no response) in 14, grade II (50-90% necrosis) in four, grade III (> 90% necrosis) in eight, and grade IV (no viable cells) in seven cases. An overall objective response rate of 73% was obtained. With the mean follow-up period of 58 months (5-101 months), the overall 5-year cumulative survival rate ascertained with the Kaplan-Meier method was 63% and that of stage II patients 81%. Eight of the nine stage III patients died of metastatic disease within two and a half years from the beginning of the treatment. In conclusion, caffeine-potentiated chemotherapy and limb-sparing surgery brought good results for stage II nonmetastatic soft-tissue sarcomas. The problem of treatment for stage III metastatic soft-tissue sarcomas, however, remains unsolved.