Capecitabine/Irinotecan Combination Regimens Active as First-Line Treatment of Metastatic Colorectal Cancer

SAN FRANCISCO-Two phase II trials found capecitabine(Drug information on capecitabine) (Xeloda) active as first-line treatment with irinotecan(Drug information on irinotecan) and well tolerated in patients with metastatic colorectal cancer, researchers reported in poster presentations at the Gastrointestinal Cancers Symposium. Flat-Dose Regimen
Howard A. Burris, MD, Director of Drug Development at the Sarah Cannon Cancer Center, Nashville, Tennessee, and his colleagues reported their early results "show that continuous flat-dose capecitabine plus weekly irinotecan [Camptosar] is a feasible and active first-line treatment for metastatic colorectal cancer, achieving disease control in two-thirds of patients." They said the antitumor activity observed is similar to that achieved with irinotecan plus bolus or infused fluorouracil(Drug information on fluorouracil)/leucovorin (5-FU/LV) (abstract 229). In their multicenter study, Dr. Burris and associates evaluated continuous, flat-dose capecitabine (1,000 mg twice daily) plus weekly irinotecan in patients with previously untreated metastatic or locally advanced colorectal cancer. They enrolled 62 patients (35 male, 17 female, median age 65 years), most of whom had only poorly or moderately differentiated tumors. Among 49 evaluable patients, objective responses have occurred in 15 patients (31%), including unconfirmed responses in five. Disease was stabilized in a further 15 patients (31%, unconfirmed in three), yielding a disease control rate of 61%. Currently, median time to progression is 5.4 months, and median overall survival is 16.7 months, Dr. Burris told ONI. Adverse events were predominantly (90%) mild to moderate and none occurred at grade 4 intensity. The most common adverse events were gastrointestinal: diarrhea (60%) and nausea/ vomiting (46%), which occurred at grade 3 intensity in 17% and 12%, respectively. Grade 3/4 neutropenia did not occur. Adverse events led to dose modification in 31 patients (60%), but only nine discontinued study treatment. Only 8% of the patients had grade 1 hand-foot syndrome, which amounted to a little redness that disappeared with a 2-day break from the drug, Dr. Burris said. "By giving a virtually nontoxic regimen," he added, "we're still ending up with a response greater than 30%," and the pill form of capecitabine simplifies administration. XELIRI
Yehuda Z. Patt, MD, chief of gastrointestinal oncology at the University of Maryland Greenebaum Cancer Center, reported on results of a multicenter trial that combined 2 weeks of capecitabine and 3-weekly irinotecan (XELIRI) as a first-line therapy in the treatment of metastatic colorectal cancer (abstract 228). For the trial, researchers enrolled 52 patients (29 male, 23 female), with a median age of 58 years. Most had liver metastases (77%), multiple metastatic sites (73%), and poorly/moderately differentiated tumors (78%). Patients were treated with IV irinotecan 250 mg/m² on day 1 plus oral capecitabine 1,000 mg/m² twice daily from day 1 (PM) until the morning of day 15, every 21 days, with startingdose reduction to 75% in patients who were 65 years or older or had renal impairment. Objective responses were achieved in 24 patients (46%) and XELIRI demonstrated considerable activity in poor-risk subgroups, including those with Karnofsky performance status less than or equal to 80% (33%), with prior neoadjuvant therapy (30%), or age greater than 60 years (41%). Only five patients experienced grade 4 adverse events, and grade 3 hand-foot syndrome occurred in only 6%. Grade 3-4 neutropenia occurred in only 25% of patients and was therefore less common than reported with the IFL regimen (incorporating bolus 5-FU/LV) or FOLFIRI (infused 5-FU/ LV). Most patients (86%) required dose modification to manage adverse events, but only 12 patients withdrew because of adverse events. There have been no treatment-related deaths. The researchers concluded that XELIRI is a highly active first-line treatment for metastatic colorectal cancer, achieving similar efficacy and favorable safety compared with IFL and FOLFIRI. They noted that XELIRI is also more convenient compared with regimens containing infused 5-FU/LV.