Impact of Young Age on Treatment Efficacy and Safety in Advanced Colorectal Cancer: A Pooled Analysis of Patients From Nine First-Line Phase III Chemotherapy Trials

• Published in: Journal of clinical oncology Vol. 29; no. 20; pp. 2781 - 2786
• Main Authors: BLANKE, Charles D, BOT, Brian M, THOMAS, David M, BLEYER, Archie, KOHNE, Claus-Henning, SEYMOUR, Matthew T, DE GRAMONT, Aimery, GOLDBERG, Richard M, SARGENT, Daniel J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.07.2011
• Subjects: Adolescent; Adult; Age Factors; Aged; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Clinical Trials, Phase III as Topic; Colorectal Neoplasms - drug therapy; Diarrhea - chemically induced; Drug-Related Side Effects and Adverse Reactions; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Irinotecan; Logistic Models; Medical sciences; Middle Aged; Multivariate Analysis; Nausea - chemically induced; Neutropenia - chemically induced; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; ORIGINAL REPORTS; Oxaliplatin; Proportional Hazards Models; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Stomatitis - chemically induced; Survival Analysis; Treatment Outcome; Tumors; Phase III trial; Human; Rectal disease; Treatment efficiency; Colorectal cancer; Malignant tumor; First line treatment; Colonic disease; Chemotherapy; Treatment; Cancerology; Digestive diseases; Intestinal disease; Advanced stage; Age; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.33.5281

Colorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. A total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P < .001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.