J. S. MITCHELL 



administered by intramuscular injection. Of particular interest are the results 

 obtained in carcinoma of the mouth and carcinoma of the ovary. Of 

 interest is the frequent clinical observation of focal pain and sensations in 

 the region of the tumour after intravenous injection of large doses of 

 Compound I. 



The preliminary clinical studies of the influence of the ancillary use of 

 the compound on the svuvival times of inoperable cases of carcinoma of 

 the bronchus treated by X-ray therapy have been discussed in detail. The 

 evidence obtained was sufficiently suggestive to justify further work, but the 

 methods used were clearly inadequate. 



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

 of any proposed method of 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 each 

 individual patient that form of treatment which is the best according to 

 present knowledge at the beginning of the investigation. Accordingly, it is 

 often necessary to plan to depart from what might be termed the theoretically 

 ideal form of experiment with deliberate sacrifice of some information. In 

 the present example, cases were allocated at random with the aid of a table 

 of random numbers to one or two alternative forms of treatment, X-ray 

 therapy combined with the compound administered by intravenous injec- 

 tion and X-ray therapy combined with the compound administered by 

 intramuscular injecdon, the latter being regarded as the control group. This 

 type of design of a clinical therapeutic trial must be justified a posteriori. 

 This has been done, and includes consideration of all the various factors 

 which may be relevant. To date, this trial includes 173 patients but the 

 follow-up must be continued. Already for the first 91 cases the two groups 

 are substantially identical in composition and there is evidence of a small but 

 definite improvement in survival of the male patients with reasonably 

 certain diagnosis (excluding those treated surgically) in the group treated 

 with X-ray therapy combined with intravenous compound in relation to 

 those in the group treated with X-ray therapy combined with intramuscular 

 compound. Statistical details have been published (MitchelP, 1953, 

 especially Table II). In general terms, in comparable groups of cases of 

 inoperable carcinoma of the bronchus, the mean survival time after the 

 first X-ra\' treatment was only about 4 months with X-ray therapy only, 

 about 6 months with X-ray therapy combined with intramuscular compound 

 and about 1 1 months with X-ray therapy combined with intravenous com- 

 pound. The improvement in this last group is certainly in accordance with 

 clinical impressions and indicates a small prolongation of useful life. The 

 mean interval from the first symptom to the first X-ray treatment is about 

 7 (6 8) months in all the groups. One unsolved problem to which much 

 attention is being devoted is to decide when to stop a clinical trial such as the 

 present one. 



It is concluded that the results obtained so far indicate that intravenous 

 administration of Compound I has a small but useful eflfect as a clinical 

 radio-sensitizer. Even though large eff"ects have not been produced, the 

 results provide evidence that it is possible to improve the response of some 



179 



