Plasma camptothecin (NSC-100880) levels during a 5-day course of treatment: relation to dose and toxicity
Creaven, P.J.; Allen, L.M.; Muggia, F.M.
Cancer ChemoTherapy Reports 56(5): 573-578
1972
ISSN/ISBN: 0069-0112 PMID: 4652588 Document Number: 5631
A simplified method of determining plasma camptothecin levels has been developed. Minimum plasma camptothecin levels (C,,, 5) during each 24-hour period of a 5-day course of daily treatment were determined in 15 patients to study the relation between C.," values and the development of hematologic toxicity. Mean Qui. values ranged from 0.17 to 1.23 μg of camptothecin/ml of plasma and did not appear to be correlated with dose in the range of doses studied (6.25-20 mg/m2/day × 5). Correlation of mean values with hematologic toxicity was fair for 13 patients in whom toxicity could be evaluated. One of the eight patients in whom toxicity did not occur had a mean value of more than 0.5 μg/ml; one of the five patients in whom hematologic toxicity did occur had a C"," value of less than 0.5 μg/ml. Although camptothecin is highly bound to human serum albumin (HSA) (equilibrium dialysis indicates that the binding constant is 6 × 107 M-1 and that the value for is 0.8), toxicity was not related to HSA concentration, total plasma protein levels, or the use of drugs which bind to HSA. We conclude that daily measurement of C,nin levels is useful in monitoring daily treatment with camptothecin although it is not an absolute predictor of toxicity.
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