On March 22, 2006, the U.S. Food and Drug Administration (FDA) approved docetaxel (Taxotere® Injection Concentrate, made by Sanofi-Aventis) for use in combination with cisplatin and fluorouracil for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease.
This indication is based on the results of a multicenter, open-label, comparative clinical trial of 457 patients with locally advanced or metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for advanced disease. Patients were randomized to one of two arms.
- TCF (docetaxel 75 mg/m² in combination with cisplatin 75 mg/m² on Day 1 and fluorouracil 750 mg/m²/day by continuous infusion for five days every three weeks), or
- CF (cisplatin 100 mg/m² on Day 1 and fluorouracil 1000 mg/m²/day by continuous infusion for five days every four weeks). Four hundred and forty five patients were treated (TCF = 221, CF = 224)
Time-to-progression (TTP) was the trial’s primary endpoint and was defined as time from randomization to disease progression or death from any cause within 12 weeks of the last evaluable tumor assessment or within 12 weeks of the first infusion of study drugs for patients with no evaluable tumor assessment after randomization.
The hazard ratio (HR) for TTP was 1.47 (CF/TCF, 95 percent CI: 1.19-1.83) with a significantly longer TTP (p=0.0004) in the TCF arm. The median TTP in the TCF arm was 5.6 months compared to 3.7 months in the CF arm.
Overall survival was significantly longer (p=0.02) in the TCF arm with a HR of 1.29 (95 percent CI: 1.04-1.61). The median survival was 9.2 months in the TCF arm and 8.6 months in the CF arm.
Compared to patients receiving CF, patients receiving TCF had more neutropenia, fever, infection, febrile neutropenia, neutropenic infection, allergic reactions, fluid retention or peripheral edema, neurosensory toxicity, dizziness, alopecia, rash, nail changes, diarrhea, esophagitis/dysphagia/odynophagia, gastrointestinal pain or cramping, and tearing than patients receiving CF.
Eighty-two percent of patients on the TCF arm had grade 3 or 4 neutropenia and 32 percent had febrile neutropenia or neutropenic infection. The most frequent causes for treatment discontinuation were GI toxicities, flu-like symptoms and neurosensory toxicity. Patients receiving CF had more thrombocytopenia, vomiting, anorexia, constipation, and altered hearing.
For gastric carcinoma, the recommended dose of docetaxel is 75 mg/m2 administered as a one-hour infusion, followed by cisplatin 75 mg/m2, as a one-to-three hour infusion (both on Day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous infusion for five days, starting at the end of cisplatin infusion. Treatment is repeated every three weeks.
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