The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.
LOS ANGELES-Bevacizumab(Avastin) plus fluorouracil (5-FU)/leucovorin (LV) can improve outcomesin patients with metastaticcolorectal cancer who are not candidatesfor initial therapy with irinotecan(CPT-11, Camptosar), accordingto results of a phase II trial (abstract3516)."Avastin, when combined withchemotherapy in these patients withmetastatic colorectal cancer, improvessurvival and improves response rates,"said lead investigator Fairooz F.Kabbinavar, MD, associate professorof medicine, University of California,Los Angeles. "This improvement inefficacy was not associated with anincrease in toxicity."The patients were randomized toreceive the Roswell Park 5-FU/LV regimenwith or without bevacizumab5 mg/kg IV every 2 weeks. Addingbevacizumab significantly prolongedmedian progression-free survival timeby nearly 4 months and there was atrend toward improved response rate,duration of response, and survival. Notably,there was a significant survivalbenefit reported for patients who hadlow serum albumin at study entry.
"The study looks at patients whoare elderly, who have lost a little bit ofweight, who are not 100% functional,who may have received prior radiation-patients who would not be ableto tolerate a full-dose regular chemotherapycombination," Dr. Kabbinavarsaid. "For them, it's a very effectivealternative regimen."A total of 209 patients received either5-FU/LV/bevacizumab or 5-FU/leucovorin/placebo. Patients were eligiblefor the study if they were judgedas not optimal candidates for irinotecan-based therapy and had one of thefollowing risk factors at baseline: age65 years or older, Eastern CooperativeOncology Group (ECOG) performancestatus 1 or 2, serum albumin of3.5 g/dL or less, or prior radiotherapyto the pelvis or abdomen.Survival Benefit
Progression-free survival time inthe bevacizumab-treated patientgroup was 9.2 months vs 5.5 monthsin the placebo arm (hazard ratio [HR]=0.50, P = .0002). There was a trendtoward improved median survival timein the bevacizumab arm, 16.6 monthsvs 12.9 months for placebo arm (HR =0.79, P = .16). The response rate wasalso somewhat higher in the bevacizumabarm, 26% vs 15.2% for placebo( P = .55).Low serum albumin at baseline wasassociated with a significant survivalbenefit. Patients with serum albuminof 3.5 g/dL or lower had a mediansurvival time of 15.3 months in thebevacizumab arm and 7.5 months inthe placebo arm (HR= 0.46, P = .001).Otherwise, results by baseline risk factorswere "generally consistent" withthe overall results, investigators said.At 60 days, all-cause mortality washigher in the placebo group, 13.5% vs5% in the bevacizumab group. Grade3 hypertension was increased in thebevacizumab group but was readilymanaged with medication, investigatorssaid. The safety data also includedreports of two cases of gastrointestinalperforation (2%) in the bevacizumabarm, consistent with what has beenfound in previous investigations (seeTable 1).Strengthening the Evidence
This trial reported by Dr. Kabbinavarwas a smaller companion trial tothe larger phase III trial (N Engl J Med350(23):2335-2342, 2004) showingthat bevacizumab prolongs survivalwhen added to irinotecan/5-FU/LV(IFL). Reported median survival timein the larger trial was 15.6 months forIFL alone, and 20.3 months for IFLplus bevacizumab ( P < .001)."Together with the larger phase IIItrial results...these data strengthen theevidence that bevacizumab-basedtherapy should be a standard optionfor the initial treatment of metastaticcolorectal cancer," the investigatorsconcluded.