Selective treatment of metastatic lymph nodes with combination of local hyperthermia and temperature-sensitive liposomes containing bleomycin.

Temperature-sensitive liposomes are designed to break down and release their contents preferentially at temperatures attainable by local hyperthermia. The antitumor effects of hyperthermia and anticancer drugs selectively delivered by temperature-sensitive liposomes in metastatic lymph nodes in rats were determined. Temperature-sensitive liposomes containing bleomycin (BLM) were injected sc into the dorsal surface of the right hindfoot of rats bearing AH66 ascites tumor implanted 7 days previously into a right popliteal lymph node. To break down these temperature-sensitive liposomes preferentially in the metastatic lymph nodes and to achieve the synergistic effects of local hyperthermia and BLM, we applied local hyperthermia to the right popliteal lymph node by making use of a water bath at 44 degrees C for 20 minutes. There was a significant difference in suppression of tumor growth and prolonged survival in rats receiving both temperature-sensitive liposomes containing BLM and local hyperthermia, compared with groups receiving hyperthermia alone, water solution of BLM alone, or a combination of both (P less than 0.05). The possibility that hyperthermia plus temperature-sensitive liposomes will enhance therapy for patients with metastatic lymph nodes warrants attention.