Taxotere shows significant survival benefit in the treatment of advanced gastric cancer

Final results from the largest international study in the treatment of advanced stomach cancer, also known as gastric cancer, demonstrated that patients who received a Taxotere (docetaxel) Injection Concentrate-based chemotherapy regimen (Taxotere, cisplatin and 5-fluorouracil) had significantly improved overall survival rates compared to patients who received a standard treatment (cisplatin and 5- fluorouracil).

Overall survival was longer with the Taxotere-based regimen with a statistically significant risk reduction of 23 percent in mortality at the time of median follow-up of 23 months. In addition, the study findings showed that twice as many patients treated with the Taxotere-based regimen were alive (18 percent) compared to those treated with standard therapy (9 percent) after 23 months of follow-up, which was statistically significant. Final results of the landmark study were presented at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida.

"These findings demonstrate that patients with advanced stomach cancer lived longer when we added Taxotere to a standard treatment regimen," said Jaffer A. Ajani, MD, Professor, GI Medical Oncology, the University of Texas M.D. Anderson Cancer Center, who is the lead investigator of this study. "This is the first time in a randomized study we are observing an 18 percent two- year survival rate for this disease."

Patients in the study also had a significant improvement in time to tumor progression (5.6 months vs. 3.7 months, p=0.0004) and a significantly better rate of tumor response (37 percent vs. 25 percent, p=0.01) with the Taxotere-based regimen.

"This may be one of the most promising finding in the treatment of advanced gastric cancer in recent years," said Vladimir Moiseyenko, MD, Professor, Petrov Research Institute of Oncology, St. Petersburg, Russia. "Adding Taxotere to this current treatment regimen may contribute to an advance in the management of the disease."

Locally advanced or metastatic gastric cancer (MGC) has a poor prognosis with 2-year survival of only 11.5 percent. This study was undertaken to study the benefits of adding Taxotere to a standard chemotherapy regimen. The primary study endpoint was time to tumor progression (TTP), and the trial was equally powered to detect a benefit in overall survival (OS).

Patients in the study included those with locally recurrent or metastatic gastric adenocarcinoma and measurable/evaluable disease who had not previously been offered chemotherapy. Twenty-two percent of the patients had carcinoma of the gastroesophageal junction. The median cycles of treatment to patients in the study were six cycles of TCF (Taxotere, cisplatin and 5-FU) or four cycles of cisplatin plus 5FU (CF). Tumor assessments were performed every 8 weeks and reviewed by independent experts.

The Taxotere (docetaxel) combination resulted in an increased incidence of low white blood cell counts (82.3% vs. 56.8%), diarrhea (20.4% vs. 8%), and infection (16.3% vs. 10.3%). Supportive measures are available to manage these problems. In this treatment arm, 81.4% of the patients experienced at least one grade3/4 side effect versus 75.4% in the control arm.

"In this sick patient population, the tolerability of cytotoxic regimens is limited. However, Taxotere combined with cisplatin plus 5FU (CF) along with appropriate risk management shows promise in the treatment of advanced stomach cancer," said Professor Eric Van Cutsem from the University Hospital of Gasthuisberg, Leuven, Belgium, a principal investigator of the TAX325 trial.

Results of the interim analysis were presented at the American Society of Clinical Oncology (ASCO) annual meeting in 2003.

An estimated 21,860 Americans (13,510 men and 8,350 women) will be diagnosed with gastric cancer during 2005, with an estimated 11,550 deaths. Globally, gastric cancer is the fourth most common cancer worldwide. Approximately 870,000 new cases are diagnosed annually worldwide, and 650,000 are expected to succumb to the disease.

Taxotere, a member of the taxane class of chemotherapeutic agents, inhibits cancer cell division by "freezing" the cell's internal skeleton, which is comprised of microtubules. Microtubules assemble and disassemble during each cell cycle. Taxotere promotes their assembly and blocks their disassembly, thereby preventing many cancer cells from dividing and resulting in death in some cancer cells.

Taxotere is currently approved in the United States to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy, and it is also approved in combination with doxorubicin and cyclophosphamide (TAC regimen) for the adjuvant (post surgery) treatment of patients with operable, node-positive breast cancer. Taxotere is approved for the treatment of patients with unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with cisplatin, who had not received prior chemotherapy. It also is approved for patients with unresectable locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy. On May 19, 2004, the U.S. Food and Drug Administration granted approval of Taxotere for use in combination with prednisone as a treatment for men with androgen-independent (hormone- refractory) metastatic prostate cancer.

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