Survival Analysis of Drug Combinations Using a Hazards Model with Time-Dependent Covariates

Publication Type
Journal Article
Year of Publication
1980
Authors
Stablein, D M; Carter, W H; Wampler, G L
Secondary
Biometrics
Volume
36
Start Page
537
Pagination
537-546
Date Published
09/1980
Keywords
Altretamine; Animals; Antineoplastic Agents; Disease Models, Animal; Drug Therapy, Combination; Female; Leukemia L1210; Mice; Razoxane; Risk
Abstract

Hazard functions in cancer chemotherapeutic situations may not be proportional, so a nonproportional hazard model has been developed. The dose-response surface is explored by regression analysis of experimental data, and after the estimation of the underlying hazard function the quality of the fit of the model is assessed. Further, treatment levels may be optimized, and estimated survival distributions can be plotted for any treatment combination. In an example of two-drug treatment of murine L1210 leukemia, statistically significant nonproportionality is determined. Analysis permits extraction of potentially important information on drug interrelationships, which has been previously unavailable.