Jaffer A. Ajani

Multicenter Phase II Trial of S-1 Plus Cisplatin in Patients With Untreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

PURPOSEnS-1 plus cisplatin is considered highly active in Japanese gastric cancer patients. We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination.nnnMETHODSnPatients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at 25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance status (KPS) of > or = 70% and near-normal organ function were eligible. All patients provided a written informed consent. To observe a 45% confirmed overall response rate (ORR), 41 assessable patients were needed.nnnRESULTSnAll 47 patients were assessed for safety and survival, and 41 patients were assessed for ORR. The median age was 56 years and median KPS was 80%. The median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI, 35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71% of patients were alive, with a median survival time of 10.9 months. Frequent grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile neutropenia (2%) were uncommon. There was one (2%) treatment-related death.nnnCONCLUSIONnS-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.

Chemotherapy for Advanced Gastric Cancer: Results from Western Clinical Trials

Current treatments for advanced gastric cancer are mainly palliative though the role of chemotherapy is evolving. Reference regimens vary, depending on the region and cultural preferences and in the United States, a combination of 5-fluorouracil and cisplatin is often used in untreated patients with advanced gastric cancer. There is a renewed interest in developing newer standards given the availability of novel agents including irinotecan, taxanes (paclitaxel and docetaxel), oxaliplatin and novel oral fluoropyrimidines like S-1. These have been used in the last five years either singly or in combination with promising results. We anticipate that with trials combining these agents, improved methodologies with appropriate endpoints, as well as the availability of molecular profiling techniques and a better understanding of molecular targets, we will be able to develop better treatments for patients with advanced gastric cancer.

Combined Modality Therapy for Gastric, Pancreatic, and Biliary Tract Carcinomas

Localized cancers are not often treated using a single modality. Rather, they are approached in a multidisciplinary manner. This approach has evolved over the past 15 yr to include medicine, surgery, radiation oncology, and gastroenterology.