Phase I study of pemetrexed plus cisplatin in unresectable, advanced gastric carcinoma in Taiwan

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14009 Background: Phase I of this Phase I/II study (H3E-AA-S038) was conducted to determine the recommended dose of pemetrexed (PT) when given with cisplatin (Cis) to patients with unresectable, advanced gastric carcinoma. Methods: Patients 18 to 70 years of age, with stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0 or 1 were included. Patients received PT and Cis on Day 1 every 21 days. Cis was dosed at 75 mg/m2. PT dosage was planned at 600, 700, 800, and 900 mg/m2. Vitamin B12 and folic acid supplementation, and dexamethasone (or equivalent corticosteroid) prophylaxis were required. The initial number of patients to be enrolled per dose level (DL) was 3. If 0/3 patients had dose-limiting toxicity (DLT), PT dose was escalated. If 1/3 patients had DLT, 3 more patients were enrolled at that DL. If ≥2 patients had DLT, the dose was not escalated further. The recommended dose of PT for Phase II was the highest dose at which <2/6 patients experienced DLT. The following toxicities were defined as DLT: death due to toxicity; neutropenia [<0/5 × 109/L for ≥5 days, or <1.0 × 109/L with fever (≥38.5 ºC)]; thrombocytopenia (<10.0 × 109/L, or <50.0 × 109/L with bleeding); AST or ALT >20 × ULN; and non-hematological toxicities of CTC grade 3 or 4 (except nausea and vomiting). Intra-patient dose escalation was not permitted. Results: Sixteen patients were enrolled. The mean (±SD) age of enrolled patients was 52.8 (±10.0) years, and the majority were male (62.5%). At DL1, 0/3 patients experienced DLT. At DL2, 1/6 patients had DLT. At DL3, 3/7 patients had DLT, and so PT dose was not escalated. All DLTs occurred in cycle 1; 2 involved neutropenia, 1 tumor hemorrhage, and 1 hypokalemia. Grade 3/4 toxicities were experienced by 12/16 (75%) patients, including 9 (56%) hematological and 10 (63%) non-hematological events. Five out of thirteen (38%) patients with measurable disease had a RECIST response (2 had a complete response, 1 each at DL1 and DL2; 3 had a partial response, 2 at DL2 and 1 at DL3). At this interim analysis, 2 patients were still on therapy. Conclusions: The recommended dose of PT is 700 mg/m2. Phase II will examine response and safety of PT plus Cis in advanced gastric carcinoma. [Table: see text]