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Clinical Benefit With Docetaxel Plus Fluorouracil and Cisplatin Compared With Cisplatin and Fluorouracil in a Phase III Trial of Advanced Gastric or Gastroesophageal Adenocarcinoma: The V-325 Study Group

Jaffer A. Ajani, Vladimir M. Moiseyenko, Sergei Tjulandin, Alejandro Majlis, Manuel Constenla, Corrado Boni, Adriano Rodrigues, Miguel Fodor, Yee Chao, Edouard Voznyi, Cindy Marabotti, Eric Van Cutsem

From The University of Texas M.D. Anderson Cancer Center, Houston, TX; N.N. Petrov Research Institute of Oncology, St Petersburg; N.N. Blokhin Cancer Research Center; Russian Scientific Centre of Radiology, Moscow, Russia; Fundación Arturo López Pérez; Hospital Clínico Universidad de Chile, Santiago, Chile; C.H. de Pontevedra, Pontevedra, Spain; Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; Hospitais da Universidade de Coimbra, Coimbra, Portugal; Taipei Veterans General Hospital, Taipei, Taiwan; Sanofi-aventis, Antony, France; and the Leuven University Hospital, Leuven, Belgium

Address reprint requests to Jaffer A. Ajani, MD, Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Box 426, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: jajani{at}mdanderson.org

Purpose For patients with advanced gastric or gastroesophageal cancer (AGGEC) providing clinical benefit with improved palliation is highly desirable. However, a prospective evaluation of clinical benefit in AGGEC patients has never before been reported in a phase III setting.

Patients and Methods In a multinational trial (V325), 445 patients were randomly assigned and treated with either docetaxel plus cisplatin and fluorouracil (DCF) or cisplatin and fluorouracil (CF). Clinical benefit was prospectively evaluated in this trial as a secondary end point. The primary measure for clinical benefit analysis was time to definitive worsening by one or more categories of Karnofsky performance status (KPS). Secondary clinical benefit end points included time to 5% definitive weight loss, time to definitive worsening of appetite by one grade, pain-free survival (defined as time to first appearance of pain), and time to first cancer pain-related opioid intake. Clinical benefit assessments were recorded at each clinic visit.

Results Clinical benefit assessments were performed in more than 75% of patients throughout V325. DCF significantly prolonged time to definitive worsening of KPS compared with CF (median, 6.1 v 4.8 months; hazard ratio, 1.38; 95% CI, 1.08 to 1.76; log-rank P = .009). Although time to definitive weight loss and time to definitive worsening of appetite favored DCF, the results were not statistically significant. Pain-free survival and time to first cancer pain-related opioid intake were comparable.

Conclusion To our knowledge, V325 is the first phase III trial to report clinical benefit in AGGEC patients. Clinical benefit was assessed beyond protocol-specific chemotherapy. The addition of D to CF not only significantly improved clinical benefit but also improved quality of life, time to progression, and overall survival compared with CF.

Supported by Sanofi-aventis.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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• Doubts About Whether Docetaxel, Cisplatin, Plus Fluorouracil Has Any Benefit in Advanced Gastric Cancer
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