Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer agents or radiation. We began clinical use of caffeine-potentiated chemotherapy for malignant bone and soft tissue tumors in 1989. Herein, we report clinical observations suggesting that caffeine-potentiated chemotherapy may produce improved outcomes compared with historical controls. For this chemotherapy, we utilized ifosfamide, or the combination of cisplatin and doxorubicin, combined with caffeine. In all variants of the caffeine-potentiated chemotherapy protocol, we administered a major tranquillizer to reduce possible caffeine-induced sleep disturbances. Also, to prevent severe adverse effects, we monitored serum levels of caffeine at 24, 48, and 72 hours after the start of continuous infusion at a dose of 1.5 g/m2/day. In patients with nonmetastatic high-grade osteosarcoma, the overall 5-year cumulative survival rate was 90% and the 5-year event-free survival rate was 75%. In high-grade soft tissue sarcoma patients with nonmetastatic lesions, the overall 5-year cumulative survival rate for patients with nonmetastatic sarcoma (stages II and III) was 80.7%. In cases that were radiologically evaluated as a complete response, intentional marginal excision was performed and the average functional evaluation of the patients was 91% of normal. Caffeine-potentiated chemotherapy was also used in patients with metastatic carcinoma and lymphoma. Caffeine-potentiated chemotherapy is a promising novel therapy not only for sarcomas, but also for carcinomas. Future studies require randomized, controlled trials.
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