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| From OncoLog,
February 2009, Vol. 54, No. 2 |
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Gefitinib Compares Favorably to Docetaxel in Lung Cancer Trial
A large M. D. Anderson–led clinical trial of the biologic therapy gefitinib (Iressa) has shown it to be as effective as the cytotoxic chemotherapy docetaxel (Taxotere) against previously treated advanced non–small cell lung cancer. The phase III trial also showed that gefitinib, an orally administered tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), caused fewer side effects than docetaxel.
“This is the largest head-to-head trial comparing an oral biologic therapy to chemotherapy in lung cancer patients, and it’s the first time that the two therapies have been shown to yield a similar overall survival benefit,” said lead author Edward S. Kim, M.D., an assistant professor in the Department of Thoracic/Head & Neck Medical Oncology.
The INTEREST study was stopped early in the United States after another large study comparing gefitinib to placebo in non–small cell lung cancer showed no survival advantage. The U.S. Food and Drug Administration relabeled the drug, and it was no longer administered to new lung cancer patients. However, INTEREST continued in other countries, accruing more than 1,400 patients with locally advanced or metastatic non–small cell lung cancer that had previously been treated.
When the international INTEREST data were analyzed, the median overall survival duration for patients who received gefitinib was 7.6 months, compared to 8 months for patients who received docetaxel. The most common side effects of gefitinib therapy were rash and diarrhea, compared with the more serious low blood cell counts and infection resulting from docetaxel therapy.
Additionally, tissue samples collected from study participants were tested for mutations in the genes that control EGFR and the KRAS protein. Patients with EGFR mutations had a better response rate and progression-free survival duration with gefinitib, though overall survival was similar to chemotherapy. Patients with KRAS mutations did poorly on either gefinitib or chemotherapy.
Still, Dr. Kim said the finding that gefitinib yields similar overall survival with fewer side effects suggests that it should once again be considered for U.S. patients who have advanced lung cancer that has relapsed or is resistant to chemotherapy.
The study, published late last year in The Lancet, was funded by gefitinib manufacturer AstraZeneca. Dr. Kim has received research funding from and served as a consultant for AstraZeneca and Sanofi-Aventis, which makes docetaxel.
Nilotinib, Dasatinib Show Promise as Front-line Therapies for Chronic Myelogenous Leukemia
Nilotinib and dasatinib may be more effective than imatinib as front-line therapies for chronic myelogenous leukemia (CML), according to preliminary findings from two ongoing phase II trials at M. D. Anderson. While imatinib is the current standard agent for newly diagnosed CML, both nilotinib and dasatinib are approved by the U.S. Food and Drug Administration as second-line therapies.
“We are seeing more patients achieve complete cytogenetic response faster with either nilotinib or dasatinib than we did during clinical trials with imatinib,” said Jorge Cortes, M.D., a professor in M. D. Anderson’s Department of Leukemia and the first author of both studies. “These are early but encouraging results.” A complete cytogenic response occurs when the abnormal chromosome that causes CML completely disappears.
To date, the nilotinib and dasatinib trials have enrolled 49 and 50 patients, respectively. Nearly all patients in the nilotinib trial have had a complete response to the drug in as few as 3 months. Overall, 96% of the patients in the nilotinib trial and 98% of the patients in the dasatinib trial have achieved a complete cytogenetic response. After 1 year of therapy, 52% of the patients in the nilotinib trial and 34% of the patients in the dasatinib trial have achieved a major molecular response, a stricter measure of disease remission.
Since its approval as a front-line therapy for CML, imatinib has increased the 5-year overall survival rate for patients with the disease from 50% to 90%. While imatinib targets aberrant Bcr-Abl protein, which causes white blood cells and immature stem cells to proliferate and crowd out red blood cells and platelets, nilotinib and dasatinib target a greater range of genetic variations that lead to CML.
In each trial, doses have had to be reduced or temporarily halted for some patients because of toxicity. However, Dr. Cortes said, “Side effects so far are manageable and comparable to those seen with imatinib.”
The findings were presented at the 50th annual meeting of the American Society of Hematology and published in the meeting proceedings in Blood.
For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.
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