An important study published in the Journal of Clinical Oncology (JCO) reports that nearly 40 per cent of patients receiving the anti-cancer drug Taxotere (docetaxel) following standard chemotherapy and radiation for advanced non-small cell lung cancer (NSCLC) were still alive after three-year follow-up. The study, conducted by the Southwest Oncology Group (SWOG) was led by David R. Gandara, M.D, of the University of California (Davis), represents the longest survival reported to date in a clinical trial in patients with advanced stage IIIB NSCLC.
This study was identical in design to a prior SWOG study; same patient selection criteria and treatment regimen. The only difference was this current study included Taxotere following chemotherapy and radiotherapy and the predecessor study used cisplatin/etoposide, a widely accepted chemotherapy, instead of Taxotere, which resulted in a dramatic long-term survival improvement.
The Phase II study included 83 patients with newly diagnosed advanced NSCLC, in primary stage IIIB, and was too extensive to be treated by surgery. Stage IIIB NSCLC is an advanced form of NSCLC, typically has invaded surrounding organs and may have resulted in significant lymph node involvement. All patients first received the chemotherapy drugs cisplatin on days one and eight and etoposide every day from the first day to the fifth day of chemotherapy. This regimen was repeated four weeks later. Patients also started concurrent radiotherapy on day one which continued for five days a week for six weeks. Treatment with Taxotere was started approximately four weeks after the completion of the concurrent cisplatin/etoposide and radiation treatments. The Taxotere treatments were repeated every three weeks for a total of three cycles.
The median survival in this current study was 26 months, and the one-, two-, and three-year survival rates were 76 per cent, 54 per cent and 37 per cent respectively. This compares to a prior study that did not include Taxotere and SWOG investigators had documented one-, two-, and three-year survival rates of 58 per cent, 34 per cent, and 17per cent respectively, which was the highest survival rate that had ever been reported in pathologically staged IIIB NSCLC. This is a significant improvement on the previous SWOG trial results, in which identical initial cycles of chemotherapy and radiation were followed by two additional cycles of cisplatin/etoposide instead of three cycles of Taxotere. Results of the current study also showed that the median length of survival without disease progression was an impressive 16 months. The regimen in the trial was generally well-tolerated, with neutropenia (a decrease in white blood cells) being the most frequently observed adverse event.
Patients diagnosed with Stage I or Stage II NSCLC are generally treated by surgical removal of the primary tumor followed by close observation. A small percentage of Stage II patients are treated with either chemotherapy alone or in combination with radiation. The vast majority of Stage IIIB and IV patients are treated with either chemotherapy alone or in combination with radiation. The development of NSCLC is most often associated with a long history of smoking, and men are several times more likely than women to develop the disease. Early symptoms of NSCLC include new or persistent cough, shortness of breath, wheezing, increased sputum (sometimes containing blood), and recurrent pneumonia. Later symptoms include fatigue, decreased appetite, double vision and pain in bones, chest or abdomen. Nearly 75 per cent of patients diagnosed with NSCLC are considered either Stage IIIB or IV.
Taxotere is a key growth driver for Aventis and is the foundation of the company's oncology franchise. At the end of November 2002, the FDA approved Taxotere as first-line therapy in combination with cisplatin for patients with unresectable locally advanced or metastatic NSCLC. The European Union approval was granted in January 2003. The European labeling reflects the results of a landmark global study of NSCLC that showed 50 per cent more patients receiving Taxotere/cisplatin—compared to those receiving a standard therapy of vinorelbine and cisplatin—were alive after two years of treatment (21 per cent versus 14 per cent respectively). Perhaps as importantly, patients receiving Taxotere/cisplatin reported improvements in quality of life, and were observed to have significantly less weight loss, lower pain scores, and better performance scores than patients receiving vinorelbine/cisplatin. The study evaluated patients who were diagnosed with either Stage IIIB or Stage IV NSCLC and who had not previously received chemotherapy treatment. In addition to its clinical applications in NSCLC and breast cancer, Taxotere is being studied extensively in clinical trials for safety and efficacy in prostate, ovarian, head & neck and gastric cancers. In 2002, Taxotere sales worldwide exceeded 1 billion euros.
In addition to Taxotere, Aventis markets Campto (irinotecan), a reference treatment for advanced colorectal cancer, in countries other than Japan and North America, and Anzemet (dolasetron mesylate), a 5HT3 inhibitor for the treatment of chemotherapy induced nausea and vomiting that is marketed in North America.
Aventis also has a rich pipeline of investigational oncology compounds, including AVE-8062, a unique antivascular agent that differs from angiogenesis inhibitors in that it targets both existing and newly developing blood vessels within tumors; flavopiridol, a novel cell cycle inhibitor; novel taxoids, that may offer benefits over available taxanes; and the ALVAC cancer vaccines being developed through Aventis Pasteur. In 2002, Aventis entered a global agreement with Genta Inc. to jointly develop and commercialize Genasense, an antisense compound designed to decrease the synthesis of Bcl-2, a protein which prevents apoptosis. Genasense, currently in phase II/III clinical studies, is the first oncology drug of its kind to directly target the biochemical pathway whereby it may greatly improve the activity of different cancer therapies.