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


METHODS
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).


RESULTS
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).


CONCLUSIONS
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 tumors.
van Bree
C
C
Department of Radiotherapy, University of Amsterdam, The Netherlands.
Rietbroek
R C
RC
Schopman
E M
EM
Kipp
J B
JB
Bakker
P J
PJ
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006979:Hyperthermia, Induced; D009374:Neoplasms, Experimental / Q000628:therapy*; D051381:Rats; D012008:Recurrence; D012208:Rhabdomyosarcoma; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002945:Cisplatin