Synergistic effects of intratumor administration of cis‐diamminedichloroplatinum(II) combined with local hyperthermia in melanoma bearing mice

The synergistic effect of local hyperthermia (LHT) with intratumor injection (i.t.) of cis‐diamminedichloroplatinum (II) (DDP) was studied using a rodent model with implanted B16 melanoma tumors. The hindfoot of the C57BL/6 mouse bearing the tumor was placed in a water bath at 42.5 ± 0.2°C (intratumor temperature was at 42.3 ± 0.1°C) for 30 minutes just after local (i.t.) or systemic (intraperitoneal;i.p.) administration of DDP (1‐3 mg/kg once in experiment I and 1‐3 mg/kg three times in experiment II). The tumor growth ratio (TGR) at 7 days after treatment in the group given DDP 3 mg/kg (i.t.) with LHT was 1.1 in experiment I and 0.5 in experiment II, and there was a statistically significant difference in both experiments compared to findings in other groups ( P < 0.01). The mean survival time was 42.1 days in experiment I and 50.2 days in experiment II, with a significant difference in the latter ( P < 0.001). Thus regional injection chemotherapy given concomitantly with local hyperthermia promotes the anticancer effects and improves the prognosis without either severe renal injury or the promotion of hematogenic metastasis. © 1992 Wiley‐Liss, Inc.