Drug activity and therapeutic synergism in cancer treatment
Carter, W.H.; Wampler, G.L.; Stablein, D.M.; Campbell, E.D.
Cancer Research 42(8): 2963-2971
1982
ISSN/ISBN: 0008-5472 PMID: 6807534 Document Number: 193846
In work involving modeling of response surfaces to describe the effects of cancer chemotherapy treatments, it is important to define activity and therapeutic synergism in a statistically defensible manner. This requires the construction of confidence intervals around the estimated optimal treatment which has been achieved by use of an indirect method first proposed by Box and Hunter. Activity for a drug or a combination can be claimed at 100(1 - .alpha.)% level of confidence when the 100(1 - .alpha.)% confidence interval about the optimal treatment excludes a zero dose. Results of treatment of L1210-bearing C57BL/6 .times. DBA/2 F1 (B6D2F1) mice. Razoxane and dacarbazine show therapeutic synergism at a 95% confidence level. A 3-drug combination of 5-fluorouracil, teniposide and mitomycin C is considered. In this case, although the estimated optimum treatment includes 48.1 mg of 5-fluorouracil/kg, 15.9 mg of teniposide/kg and 3.9 mg of mitomycin C/kg, the confidence region generated failed to confirm at an 80% level of confidence that 5-fluorouracil was a necessary component of the best treatment.