New Developments in Non-Small Cell Lung Cancer

• In October 2006, the U.S. Food and Drug Administration (FDA) approved the use of bevacizumab (Avastin) in combination with carboplatin and paclitaxel for the initial systemic treatment of patients with unresectable, locally advanced, recurrent or metastatic, non-squamous, non-small lung cancer. Approval was based on an improvement in survival time in clinical trials involving 878 patients when Avastin was added to a standard chemotherapy regimen. The median survival time for patients treated with Avastin plus standard chemotherapy (carboplatin and paclitaxel) was 12.3 months as compared to 10.3 months for patients treated with standard chemotherapy alone.

• Novel therapies for non-small cell lung cancer that are currently being investigated include:

  • Anti-angiogenesis factors - these drugs are designed to interfere with the production of new blood vessels (angiogenesis) that tumor cells require to grow and spread. Examples include anti-VEGF, SU5416, endostatin, and thalidomide.

  • Receptor tyrosine kinase inhibitors - these drugs inhibit enzymes called receptor tyrosine kinases that play a role in human cancer development. Examples include ZD 1839 (Iressa), OSI-774, and pan-erbB TKI (CI-1033).

  • Monoclonal antibodies - these are a group of highly specialized antibodies that are designed to block the binding of a growth factor to its receptor on the cell surface (such as a tumor cell) and thereby interfere with the growth of the cell. Examples include transtuzumab (Herceptin), cituximab (IMC-C225), and EGFR (ABX-EGF).

  • Matrix metalloproteinase inhibitors - matrix metalloproteinases are a group of enzymes that are thought to play a role in the spread of solid tumors by breaking down collagen and other proteins that are part of the extracellular matrix. Matrix metalloproteinase inhibitors (MMPIs) are a novel group of drugs that are designed to inhibit the degradation activity of these enzymes. Examples include Pronomastat (AG 3340), Batimastat, and Marimastat.

  • COX-2 Inhibitors - this class of drugs inhibits the action of cyclooxygensase-2 (COX-2), an enzyme that has been shown to be active in a variety of human cancers including colorectal cancer and lung cancer. Examples of COX-2 inhibitors include Celebrex and Vioxx.

• Gene Therapy - there is considerable evidence that genetic mutations play a key role in the development of cancer. The goal of gene therapy is to "fix" these genetic mutations and thereby prevent the growth and spread of the tumor. A variety of different modalities of gene therapy are currently being evaluated for the treatment of a variety of cancers, including lung cancer.

• Antisense Therapy - these compounds known as antisense oligonucleotides are designed to interfere with the growth cycle of tumor cells (DNA transcription and translation) and thereby block the growth of the tumor.

• ZD 1839 (Iressa), a novel oral epidermal growth factor receptor-tyrosine kinase inhibitor, initially showed promise in clinical trials for the treatment of various solid tumors including non-small cell lung cancer. Later clinical trials of ZD 1839, however, were not as supportive in terms of a survival benefit.

• Positron Emission Tomography (PET) is emerging as a valuable tool for the management of patients with non-small cell lung cancer including detection of recurrence, evaluating response to treatment, and prognosis.

• Pemetrexed (Alimta), a new antifolate chemotherapeutic agent, has been shown to be an effective treatment option for patients with advanced NSCLC.

• Vinorelbine (Navelbine), a semisynthetic vinca alkaloid drug, has been shown to be an effective and well-tolerated palliative treatment option for elderly patients with NSCLC.

• Irinotecan (CPT-II; Camptosar) has demonstrated efficacy for the treatment of small cell lung cancer and also appears to be promising for the treatment of non-small cell lung cancer.

• Researchers are evaluating the efficacy of tirapazamine, a prototype drug for a novel class of therapeutic agents called "hypoxic cytotoxins" that are designed to target tumor hypoxia, for the treatment of non-small cell lung cancer.

• Researchers from Italy, recently reported that a surgical technique called sleeve lobectomy might be an alternative to pneumonectomy in some patients with non-small cell lung cancer.

• Researchers are evaluating the efficacy of combination therapy with exisulind and docetaxel in patients with advanced NSCLC. Exisulind is an oral anticancer agent that was originally developed for the chemoprevention of colorectal cancer and is now being investigated for the treatment of non-small cell lung cancer.

• Clinical trials are ongoing to evaluate the efficacy of trastuzumab (Herceptin), a humanized monoclonal antibody that has been approved for the treatment of advanced breast cancer, for the treatment of non-small cell lung cancer.

• Researchers are evaluating a platinum-free combination of gemcitabine, ifosfamide, and Navelbine (GIN) for the treatment of advanced non-small cell lung cancer.

• Information regarding ongoing clinical studies in your area can be obtained at the Clinical Trials Listing Service at http://www.centerwatch.com