J. S. MITCHELL 



{c) Studies of the distribution of the chemicals in the tumour and normal 

 tissues, using mainly both fluorescence methods and radioactive 

 labelling. 



(d) radiotherapeutic experiments to study radio-sensitization in trans- 

 planted tumours, mainly the Walker rat carcinoma 256. 



New compounds examined recently include tetra-sodium 6-iodo-2- 

 methyl-1 : 4-naphthohydroquinone diphosphate and 2-ethylenimino-l : 4- 

 naphthoquinone, the latter compound appearing to be of particular interest. 

 The problem of the thermal instability of Compound I appears to have 

 been solved by the finding that this thermal instability is associated with the 

 presence of an easily removable impurity so that stable aqueous solutions of 

 Compound I can now be prepared. 



An interesting experiment by Mrs. Simon-Reuss is summarized ; it appears 

 that initial treatment of chick fibroblast cultures with Compound I leads to a 

 persistence of radio-sensitivity in subcultures even after 16 passages. 



The possible mechanisms of radio-sensitization are discussed ; the selec- 

 tive sensitization of the tumour cells is envisaged as the converse of — SH 

 protection. 



Two large-scale therapeutic radio-sensitization experiments with Com- 

 pound I and Compound XXVIII have now been completed and are reported 

 in detail. With both compounds, significant radio-sensitization is observed 

 when the compound is administered by the intravenous route but not when 

 the compound is given by the intramuscular route. 



The clinical trials of tetra-sodium 2-methyl-l : 4-naphthohydroquinone 

 diphosphate (Compound I) as a radio-sensitizer are summarized. The pre- 

 liminary general survey 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 unex- 

 pectedly good clinical response is greater following radiotherapy combined 

 with the compound administered by intravenous injection than following 

 radiotherapy combined with the compound administered by intramuscular 

 injection. Of particular interest are the results obtained in carcinoma of 

 the mouth and carcinoma of the ovary. The preliminary clinical studies 

 of the influence of the ancillary use of the compound on the survival 

 times of inoperable cases of carcinoma of the bronchus treated by X-ray 

 therapy were very suggestive, but the methods of investigation used were 

 inadequate. 



It is suggested that the design of a clinical trial for quantitative evaluation 

 of any proposed treatment of cancer is one of the most important problems 

 at the present time. The most important single feature of the design is 

 random allocation of patients to two or more alternative forms of treatment. 

 At the same time it is absolutely essential to provide for the individual 

 patient that form of treatment which is the best according to present know- 

 ledge at the beginning of the investigation. A clinical trial of Compound I 

 as a radio-sensitizer in the treatment of inoperable cases of carcinoma of the 

 bronchus is discussed ; so far it includes 1 73 patients. In general terms, in 

 comparable groups of cases of inoperable carcinoma of the bronchus, the 

 mean survival time after the first X-ray treatment was about 4 months with 



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