A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma

• DOI: 10.1007/s00280-008-0807-6
• Publication Date: 2008-07-31T06:18:56Z
• Authors: Joanna M. Brell; Smitha S. Krishna...; Milind Javle; Joel Saltzman; Ira Wollner; Robert Pelley; Afshin Dowlati; Belagodu N. Kanth...; Mark D. Schluchter; Linda Rath; S. Percy Ivy; Scot C. Remick
• Keywords: Adult; Male; Adolescent; Dose-Response Relationship, Drug; Maximum Tolerated Dose; Organoplatinum Compounds; Adenocarcinoma; Middle Aged; Irinotecan; Deoxycytidine; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Humans; Camptothecin; Female; Esophagogastric Junction; Fluorouracil; Capecitabine; Aged; Neoplasm Staging

There is no standard first-line therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma and the prognosis remains poor. Our institution conducted a phase I study of oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule. The regimen was tolerated; pharmacodynamic studies revealed no drug interactions, and there was one confirmed response in a gastric cancer patient. We performed a phase II trial in advanced gastric and GEJ adenocarcinoma to determine response rate and response duration.This was a multi-center single treatment arm study involving six sites. Only prior adjuvant therapy was allowed. Patients had ECOG performance status of 0-2, adequate organ function, and were able to tolerate oral medications. All patients received oxaliplatin 60 mg/m(2) intravenously (IV) and irinotecan 50 mg/m(2) IV weekly times 4 weeks with a 2-week rest period. Capecitabine 450 mg bid orally was received on days 1 through 5 every week for 4 weeks, followed by a 2-week rest. Patients were assessed for response after the first two cycles; response duration, overall survival, and adverse events were also recorded. We estimated an improvement in historical response rate by 30% would have clinical meaning.A total of 39 patients were accrued and all were assessed for toxicity; 30 patients were evaluable for response. The median age was 57.8 years (31-79 years) and 74% were male. Two patients had a complete response, with nine patients achieving a partial response. The total response rate was 28%, with nine patients not evaluable for response. The median response duration was noted at 5.97 months and median overall survival was 8.98 months. There were no grade 5 treatment related events, with all deaths secondary to disease progression. Only five grade 4 events occurred (neutropenia, hyperkalemia, hypokalemia (2), thrombosis/embolism) without grade 4 diarrhea or sensory neuropathy.Oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule does induce responses in advanced gastric and GEJ adenocarcinoma. However, the total response rate is modest and not an improvement over other regimens.