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Bortezomib Warrants Further Study in Advanced Lung Cancer,Two Phase II Trials Suggest

Bortezomib Warrants Further Study in Advanced Lung Cancer,Two Phase II Trials Suggest

ORLANDO, Florida-Two trials with bortezomib (Velcade), one in advanced non-small-cell lung cancer (NSCLC) and the other in small-cell lung cancer (SCLC), suggest that it has some activity in advanced disease. Researchers concluded that it is premature to test bortezomib in larger trials but that it warrants further study,perhaps in combination with other agents, in both NSCLC and SCLC. NSCLC Trial vs Docetaxel In the NSCLC trial, the drug was tested in patients with stage IIIb or IV disease who had previously received one round of chemotherapy (abstract 7034). This phase II trial enrolled 158patients and randomized them to either bortezomib alone or bortezomib with docetaxel (Taxotere). Comparable Responses Response rates and survival were comparable in the two arms. Partial responses occurred in 8% of patients taking bortezomib alone and in 9% of those taking bortezomib with docetaxel. Some of the outcomes seemed to favor bortezomib in combination therapy-median time to progression was 1.5 months with bortezomib alone vs 4 months with the bortezomib/ docetaxel combination, and more patients had stable disease on the combination arm. However, 1-year survival rates were similar: 33.1% for bortezomib alone and 38.7% for the combination. Median survival time was 7.4 months for patients who received bortezomib alone and 7.8 months for those who received the two drugs combined. Toxicity was low and manageable on both arms. The results show that activity of bortezomib is comparable to that of the current, standard drugs for second- line therapy of NSCLC, said the investigators, who were led by Michael Fanucchi, MD, associate professor of hematology and oncology, Winship Cancer Institute, Emory University, Atlanta. Charles Rudin, MD, PhD, director of the lung cancer therapeutics program at Sidney Kimmel Comprehensive Cancer Center, agreed. 'Respectable Results' vs Standard Tx These are "nice results" for bortezomib, he said in his discussion, noting that the outcomes are "perfectly respectable in comparison to any of the existing therapies," and adding, "Ithink bortezomib appears to have real activity in this context-an exciting result." Although bortezomib is probably not ready for a large phase III trial, Dr. Lynch said, it would be interesting to test it in a phase II trial with other agents, particularly with drugs targeted at the epidermal growth factor receptor, or EGFR. SWOG Study in SCLC In the SCLC study, bortezomib showed less activity (abstract 7047). Conducted by the Southwest Oncology Group (SWOG), this phase II trial tested the drug as a single agent inpatients with extensive disease who had received prior platinum therapy. Patients were stratified according to whether they were sensitive or resistant to platinum therapy. Only 1 of 56 evaluable patients had a partial response and 1 had stable disease, both in the platinum-resistant group. The trial was stopped early because of the poor response rates and a higher-than-expected rate of disease progression. Combination Tx Advocated The investigators, led by Jewel Johl, MD, of the University of California, Davis, Cancer Center, concluded thatthe results do not warrant further study of bortezomib as a single agent in heavily pretreated SCLC patients. Like the NSCLC researchers, however, Dr. Johl and his colleagues think bortezomib could be active in combination with other agents. They noted that the drug, a proteasome inhibitor, has shown activity in combination with chemotherapy agents that trigger apoptosis in preclinical and phase I studies. In discussing this study, Thomas Lynch, MD, director, Center for Thoracic Cancers, Massachusetts General Hospital, Boston, agreed that further study was warranted. "I would argue that even one response to a single agent in this setting is a proof of principle," he said, adding that combinations of bortezomib and other agents should be tested. One such trial, investigating bortezomib and topotecan (Hycamtin), has already been instituted by SWOG, the investigators said.

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