Predicting genitourinary toxicity in patients receiving cisplatin-based combination chemotherapy: a cancer and leukemia group B study

Summary

Assessment of renal function prior to cisplatin chemotherapy has long been based on measurement of creatinine clearance by 24-hour urine collection (CrC _meas). Estimated creatinine clearance (CrC _est) as calculated from the patient's age, weight, and serum creatinine level has been suggested as an adequate surrogate for CrC _meas, as it provides advantages of improved convenience, decreased cost, and possibly increased accuracy. We studied 847 patients receiving cisplatin-based chemotherapy on Cancer and Leukemia Group B (CALGB) protocols to determine whether the CrC _meas, CrC _est, or serum creatinine value or the age of the patient would predict the subsequent genitourinary (GU) toxicity. Both CrC _meas (P=0.001) and CrC _est (P=0.02) were predictive of subsequent grade 2+GU toxicity, with CrC _meas being a slightly better predictor. Patient age also influenced subsequent GU toxicity, with the risk increasing with age (P=0.0008). When patients were classified by age group and by CrC _meas, distinct subgroups were identified, with differences in the risk for grade 2+GU toxicity ranging from 14% to 32%. Using a logistic model to assess the probability of grade 2+GU toxicity, we found that an age of≥60 years (P=0.005), a CrC _meas value of <75 ml/min (P=0.004), and the risk characteristics of the individual cisplatin trial were important, whereas CrC _est was not. Furthermore, CrC _est proved to be a poor predictor of a CrC _meas value of <75 ml/min, “misclassifying” nearly half of the patients to a “lower-risk” subgroup. In summary, both CrC _meas and the patient's age independently provided predictive information concerning cisplatin GU toxicity. Our data support the continued clinical usefulness of determining the CrC _meas value prior to the administration of cisplatin-based chemotherapy to most patients.