INTRAARTERIAL CISPLATIN AND CAFFEINE WITH/WITHOUT DOXORUBICIN FOR MUSCULOSKELETAL HIGH-GRADE SPINDLE-CELL SARCOMA

Abstract

We report on the effects of intraarterial cisplatin and caffeine with/without doxorubicin on high-grade spindle cell sarcomas of bone and soft tissue based on the fact that caffeine enhances cytocidal effects of DNA-damaging agents. Intraarterial cisplatin and caffeine with/without doxorubicin was preoperatively given three times to ail patients and two courses of high-dose methotrexate with the citrovorum factor and vincristine were administered to the patients with skeletal spindle cell sarcoma. Tumor response was assessed radiographically and histologically. Seventeen (90%) of 19 patients with bone sarcoma and 7 (70%) of 10 patients with soft-tissue sarcoma showed good response. All patients with osteosarcoma demonstrating good radiological response underwent marginal excision without subsequent local tumor recurrence. Histologically, there were no viable cells in resected specimen of 14 patients with bone sarcoma. Other 8 cases with soft-tissue sarcoma treated by unplanned surgery were included to assess side effects. Twenty-five out of 37 patients are still free of disease. There was local tumor recurrence in 2 patients who did not respond to the chemotherapy. Toxic effects noted in the clinical study included moderate myelosuppression, nausea and vomiting, renal insufficiency and cutaneous injury. No toxic effects were directly attributable to 1.2-1.5 g/m(2) caffeine. The intraarterial infusion of cisplatin and caffeine combined with/without doxorubicin was tolerable in all patients and led to good response in high-grade spindle cell sarcomas. In patients with good response, limb-salvage surgery can be conducted safely without local relapse and good limb function is preserved by chemotherapy and marginal excision.