HOUSTON-More than 20% of patients resistant to secondline chemotherapy for advanced non- small-cell lung cancer (NSCLC) responded to a combination of cetuximab(Drug information on cetuximab) (Erbitux) and docetaxel(Drug information on docetaxel) (Taxotere) in a phase II clinical trial reported at the 39th Annual Meeting of the Society of Clinical Oncology (ASCO). Edward S. Kim, MD, assistant professor of medicine in the Department of Thoracic Oncology, Head and Neck Medical Oncology, at the University of Texas M. D. Anderson Cancer Center, Houston, reported a 28% response rate in 47 evaluable patients. The rate was 22.2% when investigators tallied all 54 patients, including three who died of unrelated adverse events (ASCO abstract 2581). The only approved chemotherapy for second-line NSCLC is docetaxel, Dr. Kim noted. Although docetaxel has been shown to produce a response rate as high as 21%, he told ONI that 15% or less is more typical for platinum- refractory NSCLC patients. Concerning the cetuximab plus docetaxel combination, Dr. Kim said, "In a limited study, there is encouraging activity, and it warrants further investigation in a randomized setting. Is this going to cure cancer? Probably not. Could it help people live longer? Very possibly." Continued support of the investigation is uncertain, Dr. Kim noted. The issue is not scientific merit, but allocating limited resources, he said, expressing hope that funds could be found for a second randomized phase II study if a full phase III trial were not possible at this time. Phase II Results A monoclonal antibody, cetuximab targets the HER1/epidermal growth factor receptor (HER1/EGFR), which is expressed in lung cancer and many other solid tumors. Patients in the phase II trial received 400 mg/m2 of cetuximab intravenously the first week and 250 mg/m2 every week thereafter. They were given 75 mg/m2 of docetaxel intravenously every 3 weeks. One patient had a complete response, and 11 had partial responses. Another 18 had progressive disease, and 7 were not evaluable. Median progression-free survival was reported at 2.6 months for the full cohort; median overall survival was 7.5 months. The median time to disease progression was 89 days. The median number of cycles was 4, with a range of 1 to 30. These data are not final: five patients are still on study. Dr. Kim added that the results are particularly encouraging in light of the poor condition of the study population. The trial not only restricted enrollment to EGFR-positive patients who were actively failing chemotherapy, but it also insisted that patients have had disease recurrence within 3 months of their last chemotherapy. "We wanted to focus on those patients who were actively progressing on chemotherapy," Dr. Kim said. "We were dealing with a very sick population." He cited one man who died of an unrelated adverse event between cycles three and four. Although the investigators had recorded major shrinkage of the man's tumor, Dr. Kim said they could not call it a confirmed response. Four patients discontinued because of allergic reactions but the regimen was reported to be well-tolerated, with minimal toxicity. Infection in 21% of patients, fatigue in 21%, and rash in 19% were the most common grade 3 toxicities. One case of grade 4 diarrhea and two cases of grade 4 pulmonary embolus were reported. Cetuximab did not appear to interact with docetaxel in pharmokinetic data.