A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal Cancer.

Purpose: Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease.

Patients And Methods: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX).

Baseline Quality of Life is a Strong and Independent Prognostic Factor for Overall Survival in Metastatic Colorectal Cancer.

Background: Previous studies have established that higher baseline quality of life (QOL) scores are associated with improved survival in patients with metastatic colorectal cancer (mCRC). We examined the relationship between overall survival (OS) and baseline QOL.

Patients And Methods: A total of 1 247 patients with mCRC participating in N9741 (comparing bolus 5-FU/LV, irinotecan [IFL] vs infusional 5-FU/leucovorin [LV]/oxaliplatin [FOLFOX] vs.

Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741.

Purpose: With three available chemotherapy drugs for advanced colorectal cancer (CRC), response rate (RR) and survival outcomes have improved with associated morbidity, accentuating the need for tools to select optimal individualized treatment. Pharmacogenetics identifies the likelihood of adverse events or response based on variants in genes involved in drug transport, metabolism, and cellular targets.

Patients And Methods: Germline DNA was extracted from 520 patients on the North American Gastrointestinal Intergroup N9741 study.

Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741.

Purpose: In this report, we update survival (OS) and time-to-progression (TTP) data for the Intergroup trial N9741 after a median 5 years of follow-up by using risk-stratified and prognostic factor analyses to determine if treatment outcomes differ in specific patient subgroups.

Patients And Methods: A total of 1,691 patients were randomly assigned to one of seven fluorouracil-, oxaliplatin-, and irinotecan-containing regimens. OS and TTP were calculated by treatment arm and baseline risk group (on the basis of WBC, performance status, number of sites of disease, and alkaline phosphatase).

Impact of complete response to chemotherapy on overall survival in advanced colorectal cancer: results from Intergroup N9741.

Purpose: To evaluate clinical characteristics and survival outcomes among patients with locally advanced or metastatic colorectal cancer who achieve a complete response (CR) to systemic treatment either alone or with multimodality approach.

Patients And Methods: Data were collected retrospectively from CRC patients enrolled onto the phase III trial N9741, a National Cancer Institute-funded and Gastrointestinal Cancer Intergroup-sponsored study coordinated by the North Central Cancer Treatment Group. Patients were randomly assigned to combinations of oxaliplatin, fluorouracil (FU)/leucovorin (LV) and irinotecan.

Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer.

Background: Efficacy and toxicity of oxaliplatin (Eloxatin; Sanofi-Aventis, Paris, France) combined with irinotecan (IROX) were examined in 383 patients enrolled on the IROX arm of Intergroup Study N9741.

Methods: This IROX regimen was oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) administered every 3 weeks. The relation between adverse events on IROX to selected characteristics was analyzed.

Randomized controlled trial of reduced-dose bolus fluorouracil plus leucovorin and irinotecan or infused fluorouracil plus leucovorin and oxaliplatin in patients with previously untreated metastatic colorectal cancer: a North American Intergroup Trial.

Purpose: Previously, we reported results of Intergroup N9741, which compared standard bolus fluorouracil (FU), leucovorin, plus irinotecan (IFL) with infused FU, leucovorin, plus oxaliplatin (FOLFOX4) and irinotecan plus oxaliplatin in patients with untreated metastatic colorectal cancer. High rates of grade > or = 3 toxicity on IFL (resulting in some deaths) led us to reduce the starting doses of both irinotecan and FU by 20% (rIFL). This article compares rIFL with FOLFOX4.

Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17.

Purpose: Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.

Associations between plasma insulin-like growth factor proteins and C-peptide and quality of life in patients with metastatic colorectal cancer.

Objective: Predictors of quality of life (QOL) in patients with metastatic colorectal cancer are lacking. The insulin-like growth factor (IGF) family of proteins is associated with QOL in noncancer populations. We sought to study whether these proteins are associated with QOL in patients with colorectal cancer.

Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin: results from Intergroup Trial N9741.

Background: Intergroup Trial N9741 evaluated 5-fluorouracil (5-FU)/leucovorin (LV) administered in conjunction with either irinotecan or oxaliplatin in the first-line treatment of advanced colorectal carcinoma (CRC). The current report describes two treatment arms that were withdrawn from the protocol due to unexpected treatment-related toxicities and a high mortality rate. The complications observed in these arms highlight the importance of aggressive and immediate supportive care in the management of digestive toxicity.

A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.

Purpose: Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease.

Patients And Methods: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX).