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In a recent article published in the journal Cancer, a new oral drug called lonafarnib has produced promising results when combined with paclitaxel (Taxol®) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who had failed previous treatment with Taxol or Taxotere® (docetaxel).

Lung cancer is the leading cause of cancer-related deaths in the United States and Europe. The most common type of lung cancer, NSCLC, is a malignancy that arises from the tissues of the lung. Under most circumstances, NSCLC is not curable. Current treatments attempt to destroy tumor cells or prevent further tumor growth; they include surgery, chemotherapy, and radiation. Researchers are now focused on determining how to best treat patients who do not respond to first-line treatment with chemotherapy. In this recent study, the goal was to determine the safety, efficacy, and tolerability of lonafarnib when combined with Taxol, another drug commonly used for the treatment of NSCLC. Lonafarnib acts on an enzyme system of the cancer cells to disrupt cell growth and proliferation.

A total of 33 patients diagnosed with NSCLC whose disease had progressed during previous treatment with taxane-based chemotherapy (Taxol or Taxotere) were enrolled in the study. Each patient was then treated with lonafarnib at 100 mg orally, twice daily for 21 days. They also received intravenous Taxol on days one and eight of the 21-day cycle. Twenty-nine patients had measurable disease and could be evaluated for response to chemotherapy. Three of the 29 patients achieved a partial response (10%), and eleven patients had stable disease (38%). Overall, 14 of the 29 patients (48%) experienced a clinical benefit from treatment. The average overall survival was 39 weeks and the average disease-free progression survival time was 16 weeks. In general, the combination of Taxol and lonafarnib was well tolerated with minimal side effects. The most frequent side effects included fatigue (9%), diarrhea (6%), and dyspnea (6%). Only one patient experienced a significant drop in white blood counts. Serious side effects included respiratory insufficiency and acute respiratory failure; these were infrequent, however.

Researchers concluded that lonafarnib combined with Taxol was effective for the treatment of NSCLC resistant to taxanes and was generally well tolerated. Further evaluations of lonafarnib in combination with other chemotherapies and administration earlier in the disease course are anticipated. Patients who are interested in participating in clinical trials of treatments for NSCLC are encouraged to speak to their physician or visit for more information.

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Reference: Kim E, Statkevich P, Munden R, et al. Phase II Study of the Farnesyltransferase Inhibitor Lonafarnib with Paclitaxel in Patients with Taxane Resistant Non-Small Cell Lung Carcinoma. *Cancer.*2005;104: 561-569.

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