An Analysis of Comparative Trials of L-Asparaginase (NSC-109929), Cyclophosphamide and Placebo in Patients with Inoperable Bronchogenic Carcinoma Using Corrected Survival Estimates

Abstract

L-Asparaginase (NSC-109929) was compared to Cyclophosphamide and placebo in patients with bronchogenic carcinoma. L-As-paraginase when given at 1500 i.u./kg intravenously over a 30 minute period once weekly for six weeks, shortened patient survival time as compared to Cyclophosphamide or placebo. Some preparations of L-Asparaginase when administered at a dosage of 150 i.u./kg gave a beneficial effect similar to Cytoxan and superior to that of placebo while other preparations when administered at the 150 i.u./kg dose level showed a deleterious effect similar to that given by the higher doses. The shortened survival could not be correlated with any obvious drug toxicity. There is some evidence that L-Asparaginase has an inhibitory effect on T cell function and thus depresses cellular immunity. This may account for the shortened survival observed in the lung cancer patients receiving the high doses. The opposite effect seen at the low dose level suggests that an agent which interferes with host defenses at one dose level may enhance it at another. This favorable effect was not observed with all L-Asparaginase preparations. A variation in composition of preparations of L-Asparaginase, especially the endotoxin content, has been observed by others. Cytoxan increased survival by a few weeks as compared to the Placebo. This effect was consistent in the different trials. Cytoxan was equally effective in large cell, squamous cell and adenocarcinoma. Possible reasons for this are discussed in the light of the current information on the histopathology of bronchogenic carcinoma.