title: Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer.
abstract: Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m². Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity.
authors.affiliation: Oncology Center, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh, 11211, Saudi Arabia.
authors.forename: Shouki
authors.initials: S
authors.lastname: Bazarbashi
authors.affiliation: Oncology Center, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh, 11211, Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Aljubran
authors.affiliation: Oncology Center, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh, 11211, Saudi Arabia.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Alzahrani
authors.affiliation: Oncology Center, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh, 11211, Saudi Arabia.|Medical Oncology Department, Zagazig University, Al-Gamaá Road, Zagazig, Sharkia Governorate, 44519, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mohieldin
authors.affiliation: Oncology Center, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh, 11211, Saudi Arabia.|Faculty of medicine, Cairo University, Kasr Al-Ainy Street, Cairo, 11562, Egypt.
authors.forename: Hussein
authors.initials: H
authors.lastname: Soudy
authors.affiliation: Department of Biostatistics, Epidemiology and Scientific Computing, Research Center, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh, 11211, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shoukri
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069287:Capecitabine / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D002166:Camptothecin
keywords: Bevacizumab; capecitabine; irinotecan; metastatic colorectal cancer; oxaliplatin