I n t r o d u c t i o n Despite the declining incidence of gastric cancer in Western countries, gastric cancer is the most frequently diagnosed cancer worldwide, and is one of the main causes of cancer deaths [1]. In pa- tients with advanced gastric cancer with distant metastasis or re- currence, systemic chemotherapy has been recommended as standard treatment, and the prolongation of survival or increase in the quality of life is well-established [2]. However, patients with advanced gastric cancer with distant metastasis or recurrence remain incurable, and these patients have a median survival of only 7-13 months, despite receiving chemotherapy [3]. Also, first-line standard chemotherapy regimens have not been defined for patients with advanced gastric cancer. Cisplatin-based regimens have demonstrated superior efficacy com- pared to platinum-free regiments, although cisplatin-based regimens have significant toxicity [4,5]. Oxaliplatin is a third generation platinum compound with a lack of cross-drug resistance with cisplatin, a synergistic effect with 5- fluorouracil (5-FU), and a satisfactory safety profile compared to cisplatin [6-9]. Moreover, many adducts of oxaliplatin appear to be more effective in inhibiting DNA synthesis than adducts of cisplatin [10-12]. Two phase III trials have directly compared oxaliplatin-based versus cisplatin-based regimens [13,14], both of which have concluded that oxaliplatin is at least as effective as cisplatin, and has a lower toxicity profile, except neurotoxicity, in combination regimens for patients with advanced gastric cancer. In several phase II studies involving the treatment of advanced gastric cancer, various com- binations of oxaliplatin, 5-FU, and folinic acid (FA), as first- or second- line treatments, have shown considerable activity [15-19]. However, the optimal dose and schedule of combination oxaliplatin, 5-FU, and FA were not established. The aim of this retrospective study was to report the efficacy and toxicity of a biweekly protocol of oxaliplatin (100 mg/m2) combined with 5-FU (2,400 mg/m2; 46-hour continuous infusion), and FA (200 mg/m2) as first-line treatment on response, survival, and toxicity rates of metastatic and recurrent gastric cancer in Korean patients. M a t e r i a l s a n d M e t h o d s 1 Eligibility criteria The eligibility criteria were as follows: 1) histologically-confirmed metastatic or recurrent adenocarcinoma of the stomach and 18 years of age; 2) no previous chemotherapy, except post-operative adjuvant chemotherapy or chemoradiation that was received 6 months pre- viously; 3) an Eastern Cooperative Oncology Group (ECOG) perfor- mance status of 0-2; 4) no serious or uncontrolled concurrent medical illness; 5) at least one measurable lesion; and 6) adequate baseline Han Jo Kim, et al_Oxaliplatin Combination for Advanced Gastric Cancer hematologic function (absolute neutrophil count [ANC] 1.5 109/L, platelet count 100 109/L), adequate hepatic function (serum bili- rubin 1.25 upper normal limit [UNL], serum aspartate amino- transferase, alanine aminotransferase 2.5 UNL, serum alkaline phosphatase 5.0 UNL), and adequate renal function (serum creatinine 1.5 mg/dL). The exclusion criteria were as follows: 1) pre- existing peripheral neuropathy; 2) concurrent or prior malignancy, except curative resection of cervical carcinoma in situ or squamous cell carcinoma of the skin; 3) active infection; and 4) concurrent treatments that interfered with the evaluation of the study. 2 Treatment protocol and dose modifications 1) Chemotherapy protocol Oxaliplatin (100 mg/m2) and FA (200 mg/m2) were given as a 2- hour intravenous infusion followed by 5-FU (2,400 mg/m2) as a 46- hour continuous infusion every 2 weeks. Treatment was continued until disease progression, unacceptable toxicity, patient refusal, or at the discretion of the physician. Anti-emetic prophylaxis was given according to a local protocol. Granulocyte colony-stimulating factor was not routinely used in the study. 2) Treatment delays and dose modifications Each cycle was started if the ANC and platelet count on the day of treatment were 1.5 109/L and 100 109/L, respectively. In the case of toxicity grade 3, except alopecia, chemotherapy was delayed 1 week, then restarted after full recovery. A reduction of 25% in all drug doses was applied to grade 3/4 thrombocytopenia or febrile neutropenia, grade 4 neutropenia, and grade 3/4 non-hematologic toxicity in the previous cycle of chemotherapy. Response and toxicity assessment The response to treatment was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ver. 1.0) [20]. Computed tomography (CT) scans of the measurable lesions were performed within 2 weeks prior to treatment. After every 4th cycle of chemotherapy, CT scans were performed to determine the response of the disease, or sooner if there was evidence of any clinical deterioration. Complete blood cell counts with differentials and serum biochemistries were repeated prior to the start of each chemotherapy cycle, and the toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, ver.3.0). 3 4 Statistical analysis Overall survival (OS) was calculated from the first day of chemo- therapy to the date of death. Time-to-progression (TTP) was calculated from the first day of chemotherapy to the date of disease progression. The Kaplan-Meier method was used to analyze the TTP and OS, and VOLUME 43 NUMBER 3 SEPTEMBER 2011 155