Hydralazine at thermoradiotherapy: tumor size and blood flow effects.
OBJECTIVE
This study was aimed to assess the dependence on tumor size and blood flow of the efficacy of a vasoactive drug hydralazine with thermoradiotherapy.


METHODS
Experiments were performed on mice bearing SCC-VII tumors with volumes of about 85 and 340 mm3 (7-8 or 11-12 days after transplantation, respectively). Local hyperthermia (water bath, 43 degrees C, 0.5 h) was started 3 h after irradiation of tumors. Hydralazine (2.5 mg/kg, IP) was given 0.5 h before heating. Tumor blood flow was evaluated by laser Doppler flowmetry before, during and up to 2 days after the treatments.


RESULTS
It was shown that hydralazine and hyperthermia, even in combination with each other, had very weak anti-tumor effect, especially for 85 mm tumors. The agents also insignificantly enhanced the efficacy of radiotherapy excluding the case of polyradiomodification for 340 mm3 tumors when a dose modifying factor of about 2.0 was achieved. Thermometry showed only a small improvement by HDZ in heating patterns of tumors of both sizes. Meanwhile, the therapeutic efficacy of hydralazine and heat was correlated with the changes in tumor blood flow, first of all with the delayed effects. The radiomodifiers induced only minor and transient suppression of perfusion in the smaller tumors, and more markedly and for longer time decreased blood flow in the larger tumors. In the latter case, the inhibiting effect of the drug plus hyperthermia remained for at least 48 h after the treatment.


CONCLUSIONS
(a) The combined use of hydralazine and heat seems to be advisable only at radiotherapy of rather large advanced tumors; (b) the efficacy of such radiomodification is correlated with prolonged inhibition of tumor blood flow by these agents; and (c) hydralazine and hyperthermia are likely to kill selectively both acutely and chronically hypoxic radioresistant cancer cells.
Kozin
S V
SV
Department of Radiology, Kansai Medical University, Osaka, Japan.
Hasegawa
T
T
Ha-Kawa
S K
SK
Akagi
K
K
Tanaka
Y
Y
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D006830:Hydralazine / Q000627:therapeutic use*; D006979:Hyperthermia, Induced; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012039:Regional Blood Flow / Q000187:drug effects / Q000528:radiation effects
D006830:Hydralazine