LABORATORY STUDIES AND CLINICAL TRIALS 

 OF SOME CHEMICAL RADIO-SENSITIZERS 



J. S. Mitchell 

 Department of Radiotherapeutics, University of Cambridge 



This paper deals mainly with work completed and in progress during the 

 past year and is intended to supplement the review of the subject which 

 I gave in 1953 at the 7th International Congress of Radiology (Mitchell^). 



The aim of this investigation is to try to improve the results of radio- 

 therapy of some types of cancer by the ancillary use of chemical agents 

 designed to act as radio-sensitizers. It is emphasized that in general these 

 chemicals when acting alone are not chemotherapeutic agents. In addition 

 to its practical importance, the possibility of chemical radio-sensitization 

 appears to be of theoretical interest. 



The first compound studied, which is still perhaps the most interesting, 

 is tetra-sodium 2-methyl-l : 4-naphthohydroquinone diphosphate (' Syn- 

 kavit ' ; Compound I). Clinical trials of its use have been in progress since 

 November, 1946, and I have employed it in the treatment of about 1070 

 patients mainly in conjunction with radiotherapy. I wish to emphasize the 

 more recent clinical studies which are in progress and include the design of a 

 clinical trial for evaluation of a radio-sensitizer. In August, 1953, a special 

 clinical trial was started to examine the combined use of intravenous Com- 

 pound I (Synkavit), oxygen administration before and during irradiation 

 and X-ray therapy, in the treatment of some patients with advanced cancer. 



The results of various aspects of this work have been published by 

 Mitchell and Simon-Reuss^ in 1947, Mitchell^"^ in the years 1948-52, 

 Mitchell and Simon-Reuss^- ^° in 1952, Hughes and Simon-Reuss^^ in 1953. 

 In addition, a rmmber of papers dealing mainly with mitotic inhibition have 

 been published on the following groups of compounds and related aspects of 

 the problem : Certain quinones by Friedmann, Marrian and Simon- 

 Reuss^^ (1948),svilphydryl addition compounds of some quinones and related 

 compounds by Friedmann, Marrian and Simon-Reuss^^ (1948), maleimide 

 and related substances by the same authors'* in 1949, the reactions of sub- 

 stituted maleimides with thiols (Marrian'^ in 1949), the condensation of 

 N-substituted maleimides with thiourea (Marrian*^ in 1949), the action 

 of 1 : 4-naphthohydroquinone diphosphate (Friedmann and Bailey*'''), 

 unsaturated imides with special reference to their reaction with sulphydryl 

 groups (Friedmann, Marrian and Simon-Reuss^^, 1952), halogen deriva- 

 tives of the 1 : 4-naphthoquinone group and maleic acid series (Friedmann, 

 Marrian and Simon-Reuss*^, 1952), a spectrometric investigation of the 

 interaction of glutathione with maleimide and N-ethylmaleimide (Fried- 

 mann 2*^, 1952), and the action of X-rays on the glutathione 1 : 4 naphtho- 

 quinone reaction (Friedmann-^ 1954). As a different method of approach, 

 studies have been reported on the antagonization of the antimitotic action of 



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