Treatment sequencing, asymmetry, and uncertainty: protocol strategies for combination chemotherapy.

摘要: Abstract This paper summarizes a large number of simulations which relax the “symmetry” assumptions in Goldie-Coldman treatment model, was symmetrical with respect to two drugs considered for use together. The results are that, under relevant violations assumptions, non-alternating schedules frequently outperform alternation and combination substantially. magnitudes these effects at least as improvements made by shortening time periods between changes. Three protocol design strategies derived from described: (a) when there is no knowledge parameters, empirical trials search best schedule can be contemplated, if patients such have fundamentally “similar” tumors, special sense given name “pattern homogeneity”; (b) minimal cell kill parameters available, “worst drug rule” could perform remarkably well. strategy contrary much current practice, but clear rationale proposed; (c) detailed tumor available each individual, modeling predict optimal promises great outcome. Additional considerations addressed include factors determining merit strategies, suggestions new laboratory research, implications future clinical chemotherapy research.