Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer.

Purpose: Evidence suggests that lean body mass (LBM) may be useful to normalize doses of chemotherapy. Data from a prospective study were used to determine if the highest doses of 5-fluorouracil (5-FU) per kilogram LBM would be associated with dose-limiting toxicity in stage II/III colon cancer patients treated with 5-FU and leucovorin. Experimental Design: Toxicity after cycle 1was graded according to National Cancer Institute CommonToxicity Criteria, version 2.0. Muscle tissue was measured by computerized tomography. An extrapolation to the LBM compartment of the whole body was employed. Results: Mean values of 5-FU/LBM of the entire population were different in terms of presence or absence of toxicity (P = 0.036). A cut point of 20 mg 5-FU/kg LBM seemed to be a threshold for developing toxicity (P = 0.005). This observation was pertinent to women (odds ratio, 16.73; P = 0.021). Women in this study had a relatively low proportion of LBM relative to their body surface area. Conclusion: Our study shows that low LBM is a significant predictor of toxicity in female patients administered 5-FU using the convention of dosing per unit of body surface area. We conclude that variation in toxicity between females and males may be partially explained by this feature of body composition. 5-Fluorouracil (5-FU) is a potent anti-metabolite used to treata variety of solid tumors, and it is a well-established form of chemotherapy for colorectal cancer (1). The Mayo regimen of bolus 5-FU and leucovorin is associated with significant myelosuppression, mucositis, and diarrhea. In one study, 35% of patients had significant toxicity with patients experiencing dose reductions, therapy discontinuations, hospitalization, and even death (2). Attempts have been made to identify clinical variables to predict patients at risk for severe toxicity (3), but an approach for individualizing 5-FU dosing remains unclear.Interpatient variation in toxicities can arise from differences in target protein(s) expression, drug metabolism, and excretion. Disparate metabolism and excretion of anticancer drugs in turn can be due to environmental, physiologic, and genetic factors.Our hypothesis is that a physiologic factor, heterogeneous body composition of cancer patients, and, specifically, relative amounts of lean and adipose tissue compartments contribute to interpatient variation in toxicities. We propose that the size of lean and fat compartments relate to the pharmacokinetic properties of a drug, as hydrophilic drugs distribute into the lean compartment, whereas lipophilic drugs distribute into the fat compartment.Currently, for most chemotherapy, dose is determined using body surface area (BSA). The practice originated from observations that basal metabolic rates scaled between species according to weight. Early investigators used BSA to estimate an appropriate starting dose for an anticancer drug for phase I studies based on preclinical animal studies (4). BSA dosing became established in clinical settings in part by dogma and not due to s...

CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.

SummaryBackground Eff ective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specifi c cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation.

PURPOSE Immunotherapy has revolutionized the treatment of advanced non–small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m2 once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3–5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC.