LABORATORY STUDIES AND CLINICAL TRIALS OF CHEMICAL RADIO-SENSITIZERS 



human malignant tumours to radiotherapy by means of chemical radio- 

 sensitizers. 



Combination of Compound I, oxygen and X-ray therapy — Since August, 1953, a 

 clinical trial has been in progress of the combined use of intravenous Com- 

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

 and X-ray therapy in the attempted treatment of patients with advanced 

 cancer. The compound has been given in the usual manner with maximum 

 unit doses in the region of 100 to 150mg at 30 minutes before starting the 

 X-ray treatments at each visit. The oxygen is administered at atmospheric 

 pressure by means of either a B.L.B. mask or an anaesthetic mask, with a 

 flow-rate meter at about 6 litres per minute, starting usually 20 minutes before 

 and continued throughout irradiation. Every endeavour has been made to 

 employ the normal methods of X-ray therapy, often with large fields, and to 

 avoid any modification of the techniques as a result of the combined treat- 

 ment. So far 34 cases have been treated, mainly advanced cases of car- 

 cinoma of the stomach, colon, and ovary and inoperable cases of carcinoma 

 of the bronchus after thoracotomy. It is of course too early to assess the 

 results. With the combined treatment, both the skin reactions and the 

 general reactions appear to be no more severe than would be expected with 

 the X-ray therapy only. I wish to thank Dr. S. D. Sturton for his help in 

 the initial part of this investigation. These trials are being continued, 

 together with studies of the combination of oxygen and X-ray therapy. A 

 randomized trial has been started using four groups. X-ray therapy combined 

 with intramuscular Synkavit, oxygen combined with X-ray, intravenous 

 Synkavit combined with X-ray and intravenous Synkavit, oxygen and X-ray. 

 Experiments with animal tumours in these fields are being carried out by 

 Dr. D. B. Cater and Dr. A. F. Phillips. 



SUMMARY 



The aim of this investigation is to try to improve the results of radiotherapy 

 of some types of cancer by the ancillary use of chemical agents designed to act 

 as radio-sensitizers. This paper deals mainly with recent results but also 

 refers to the previous studies carried out since 1946. The first compound 

 studied, tetra-sodium 2-methyl-l : 4-naphthohydroquinone diphosphate 

 (Synkavit ; Compound I), is stiU perhaps the most interesting. Clinical 

 trials of its use have been in progress since November, 1946, and about 

 1 ,070 patients have been treated by the combination of radiotherapy with 

 this compound. 



In the laboratory studies we have used : — 



(7) tissue cultures mainly of chick fibroblasts, for the primary sorting test 



and for studies of the relation between chemical structure and biological 



action. 



{2) animal experiments with rats mainly, but also using mice and rabbits, 



for : — 



{a) tests of chemical toxicity and radiotoxicity in the case of compounds 



incorporating radio-isotopes. 

 ib) studies of radio-sensitization of normal tissues with total body radiation. 



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