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Local hyperthermia enhances the effect of cis-diamminedichloro-platinum(II) on nonirradiated and preirradiated rat solid tumors

By C. van Bree, R. C. Rietbroek, E. M. Schopman, J. B. Kipp and P. J. Bakker

Abstract

We have investigated differences in the efficacy of combined treatment with cis-diamminedichloroplatinum(II) (cDDP) and local hyperthermia (HT) in nonirradiated and preirradiated experimental tumors. Survival of R-1 rhabdomyosarcoma cells was assessed after treatment with various cDDP-concentrations at 37 degrees C and 42 degrees C in vitro. Rats bearing R-1 rhabdomyosarcomas of 190 mm3 (SE 15 mm3) were treated with cDDP (6 mg/kg i.p.), HT (1 h at 43 degrees C), or cDDP+HT (45 min interval) without preirradiation or at day 16 after the first dose of fractionated irradiation. Fractionated irradiation consisted of four daily doses of 5 Gy of x-rays each and tumor volumes had regrown to their original volume at the time of treatment. Experimental endpoint was tumor growth delay (TGD). Hyperthermia-enhanced cDDP cytotoxicity in vitro by a factor of about 5. Treatment with cDDP or HT alone resulted in a similar TGD in non- and preirradiated tumors (7.2 vs. 7.4 days and 1.1 vs. 0.9 days, respectively). In non- as well as in preirradiated tumors, HT given in combination with cDDP significantly enhanced the effect of cDDP, prolonging the TGD (11.1 days (p = 0.0001) and 16.2 days (p < 0.0001), respectively) corresponding to a TGD-enhancement of 1.54 and 2.19, respectively. The TGD after cDDP+HT in preirradiated tumors was significantly longer than in nonirradiated tumors (p = 0.0003). In this tumor model, HT enhanced the antitumor effect of cDDP. Previous radiation treatment did not reduce the HT-enhanced effect of cDDP. Combined cDDP and HT may be useful in the treatment of nonirradiated tumors as well as previously irradiated tumor

Year: 1996
DOI identifier: 10.1016/s0360-3016(96)00238-6
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Provided by: NARCIS
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