46 • Clinical Colorectal Cancer May 2004 Phase II Trial of Capecitabine/Irinotecan and Capecitabine/Oxaliplatin in Advanced Gastrointestinal Cancers Karin Jordan, 1 Olaf Kellner, 1 Thomas Kegel, 1 Hans-Joachim Schmoll, 1 Axel Grothey 2 Abstract Clinical Colorectal Cancer, Vol. 4, No. 1, 46-50, 2004 Key words: Combination therapy, Diarrhea, Gastric cancer, Hand-foot syndrome, Pancreatic cancer Introduction The benefit of systemic chemotherapy for advanced col- orectal cancer in the palliative setting has long been known. Several randomized trials in the 1980s and 1990s demon- strated that 5-fluorouracil (5-FU)–based treatment is superior to best supportive care in terms of overall survival (OS) and preservation of quality of life. 1,2 While even today 5-FU mod- ulated by leucovorin (LV) remains the backbone of most cur- rent chemotherapy protocols, treatment options for advanced colorectal cancer have expanded in recent years to include 2 non–thymidylate synthase inhibitors: irinotecan and oxali- platin. Several phase III trials have demonstrated the efficacy and safety of oxaliplatin- or irinotecan-based combination protocols with 5-FU/LV as first- and second-line therapy in advanced colorectal cancer with increased response rates, longer progression-free survival (PFS), and OS. 3-7 It is well established that the antineoplastic activity of 5-FU can be enhanced by protracted intravenous application, which Contribution Original Combination protocols of 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan or oxaliplatin have demonstrated high ac- tivity in metastatic colorectal cancer. Capecitabine, an oral 5-FU prodrug, may replace infusional 5-FU/LV in combination protocols with irinotecan or oxaliplatin. We therefore initiated a phase II study with capecitabine plus either irinotecan or oxaliplatin to determine the efficacy and toxicity of specific combination protocols in patients with advanced gas- trointestinal (GI) tumors. Capecitabine 1000 mg/m 2 taken orally twice a day on days 1-14, plus oxaliplatin 70 mg/m 2 on days 1 and 8, or irinotecan 100 mg/m 2 on days 1 and 8; repeated every 3 weeks in an outpatient setting. Patient and tumor characteristics were as follows: median age, 68 years (range, 34-77 years); sex: 10 women, 33 men; tumor types: 35 colorectal cancer; 8 other GI tumors including 5 gastric, 2 pancreatic, and 1 duodenal cancer. All 43 patients treat- ed were evaluable for toxicity (capecitabine/oxaliplatin, 24 patients; capecitabine/irinotecan, 19 patients), and 39 were evaluable for efficacy (capecitabine/oxaliplatin, 22; capecitabine/irinotecan, 17). Grade 3/4 toxicities (National Cancer In- stitute Common Toxicity Criteria Version 2.0) were limited to diarrhea, 9 patients (capecitabine/irinotecan, n = 5;cape- citabine/oxaliplatin, n = 4); hand-foot syndrome, 1 patient (capecitabine/irinotecan); nausea, 2 patients (capecitabine/ox- aliplatin); vomiting, 1 patient (capecitabine/oxaliplatin); and peripheral neuropathy, 1 patient (capecitabine/oxaliplatin). No grade 3/4 myelosuppression was noted for either protocol.Capecitabine/irinotecan and capecitabine/oxaliplatin demon- strated significant clinical activity in colorectal cancer and other GI cancers as first-line and salvage therapy. Capecita- bine/oxaliplatin and capecitabine/irinotecan show an excellent safety profile and clinical activity in colorectal cancer and other advanced GI tumors.The main toxicity in both arms was manageable diarrhea.This trial served as basis for a ran- domized multicenter phase II study comparing capecitabine/oxaliplatin and capecitabine/irinotecan as first-line therapy in patients with advanced colorectal cancer. Submitted: Dec 10, 2003; Revised: Feb 3, 2004; Accepted: Feb 9, 2004 Address for correspondence: Axel Grothey, MD, Division of Medical Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 Fax: 507-284-1803; e-mail: grothey.axel@mayo.edu 1 Department of Hematology and Oncology, University of Halle, Germany 2 Division of Medical Oncology, Mayo Clinic, Rochester, MN Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1533-0028, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.