LABORATORY STUDIES AND CLINICAL TRIALS OF CHEMICAL RADIO-SENSITIZERS 



that radio-sensitization is obtained for intravenous injection either immedi- 

 ately before or at 30 minutes before starting the X-ray treatment. 



The difference between groups C and D for intravenous injection is 

 regarded as significant. For the pooled intravenous doses x""[i]c = 5-953, 

 P = 0-014 and for the single intravenous doses only, X ^[i]c = 5-133 and 

 P = 0-023. These experiments suggest that Compound XXVIII when 

 administered by intravenous injection in doses approximately twice those 

 of Compound I is an effective radio-sensitizer for the Walker rat carcinoma 

 256, though the findings suggest that Compound XXVIII is slightly less 

 effective as a radio-sensitizer than Compound I. However, there is no very 

 convincing difference in effectiveness between the two compounds in these 

 animal experiments. 



Distribution studies — Distribution studies of Compound I in the rat with the 

 Walker carcinoma 256 have demonstrated increased fluorescence of a deri- 

 vative of the compound with Wood's light (wavelengths 3,650, 3,655 and 

 3,663 A) in the actively growing parts of the tumour and some other tissues, 

 including sternal marrow, lymphoid tissue, testis, ovary and kidney after 

 intramuscular injection. After intravenous injection with small doses there 

 is much more selective concentration of the compound in the tumour. With 

 larger intravenous doses there is spill-over into the other organs mentioned. 

 The compound responsible for the yellow fluorescence appears to be 

 2-methyl-l : 4-naphthoquinone-2 : 3-oxide, as confirmed by the fluorescence 

 spectrum. These distribution studies were summarized in Table II of 

 Mitchell^ (1953). Other compounds which accumulate in the actively 

 growing parts of the Walker rat carcinoma 256 are the tetra-sodium salts 

 of 2 : 3-dimethyl-l : 4-naphthohydroquinone diphosphate (Compound 

 XXVIII), and 2-methyl-3-bromo-l : 4-naphthohydroquinone diphosphate 

 (Compound IX). In the case of Compound IX, there is a considerably 

 lower differential absorption ratio in the tumour, as shown by fluorescence, 

 than in the case of Compound I, and this has been confirmed by Mr. D, R. 

 Maxwell by radioactive tracer studies with Compound IX labelled with 

 »2Br. Distribution studies using Compound I labefled with ^^C in the 

 methyl group are in progress. 



Clinical trials of tetra-sodium 2-rnethyl-l : 4-naphthohydroquinone diphosphate as a 



radio-sensitizer 

 Attempts to evaluate tetra-sodium 2-methyl-l : 4-naphthohydroquinone 

 diphosphate (Synkavit, Compound Ij as a radio-sensitizer in the radio- 

 therapy of maHgnant tumours have been in progress since November 1946. 

 A summary of the results as assessed on 31 May, 1953, has been published 

 (Mitchell 1). The investigation is continuing. It is emphasized that 

 in general the compound alone has no therapeutic eflfect on malignant 

 tumours. 



The preliminary general survey of the use of Compound I in the treatment 

 of patients with various types of malignant tumours other than carcinoma of 

 the bronchus with follow-up for at least 5 years, suggests that the proportion 

 of cases showing unexpectedly good clinical response is greater following 

 radiotherapy combined with the compound administered by intravenous 

 injection than following radiotherapy combined with the compound 



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