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

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Abstract
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.