Amongst eligible patients, age and comorbidity do not predict for dose-limiting toxicity from phase I chemotherapy

• Published in: Cancer chemotherapy and pharmacology 2010-03, Vol.65 (4), p.775-780
• Main Authors: LoConte, Noelle K, Smith, Maureen, Alberti, Dona, Bozeman, Jeffrey, Cleary, James F, Setala, Ashley N, Wodtke, Geoff, Wilding, George, Holen, Kyle D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; alkaline phosphatase; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; bivariate analysis; Cancer Research; Clinical trial. Drug monitoring; Clinical Trials, Phase I as Topic; Comorbidity; cytotoxicity; drug therapy; Drug toxicity and drugs side effects treatment; Drug-Related Side Effects and Adverse Reactions - chemically induced; Drug-Related Side Effects and Adverse Reactions - diagnosis; drugs; Female; General pharmacology; hemoglobin; hospitals; household income; Humans; Logistic Models; Male; marital status; maximum tolerated dose; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Multivariate Analysis; Neoplasms - drug therapy; Neoplasms - epidemiology; Oncology; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Predictive Value of Tests; Prognosis; prospective studies; Retrospective Studies; surface area
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-009-1084-8

Background There are no clear predictors clinicians can use to determine who is more likely to experience dose-limiting toxicity (DLT) in phase I chemotherapy clinical trials. Many providers are reluctant to refer older adults to phase I trials because of concerns about the development of toxicity. The goal of this study was to identify clinical and nonclinical factors which were associated with the development of DLT in phase I studies. Methods Patients (pts) were included if they were treated at maximally tolerated dose (MTD) and above. Studies were included only if MTD was reached. Data collected included age, comorbidity (Cumulative Illness Rating Score-Geriatrics), labs at enrollment, height, weight, performance status, cancer type, duration of diagnosis, prior treatment, drug level, smoking status, marital status, mean income, percent of population high school educated as determined by ZIP code, and distance to the phase I trial hospital. Those who did and did not have DLT were compared by bivariate and then multivariate analysis. Results A total of 242 charts were reviewed from 24 cytotoxic chemotherapy studies, and 27 different types of cancer were represented. On bivariate analysis, mean age, household income (higher), weight, body surface area, dose of drug, alkaline phosphatase, hemoglobin, and LDH were significantly associated with DLT (P < 0.05). CIRS-G score was not associated with DLT. In multivariate analysis, dose level (P = 0.004) and distance from the phase I trial hospital (P = 0.04) were still significant predictors of DLT. Age did not predict for severity of DLT. Conclusions Age and comorbidity did not predict for development of DLT in phase I chemotherapy trials. Many of these pts were very fit, with relatively low CIRS-G scores, so the impact of comorbidity may not have been fully evaluated. Several social and clinical factors may predict for development of DLT. A prospective study is being planned to confirm these results.