Phase I study of two schedules of oral S-1 in combination with fixed doses of oxaliplatin and bevacizumab in patients with advanced solid tumors Journal Article

  

Authors:	Chung, K. Y.; Saito, K.; Zergebel, C.; Hollywood, E.; Segal, M.; Saltz, L. B.
Article Title:	Phase I study of two schedules of oral S-1 in combination with fixed doses of oxaliplatin and bevacizumab in patients with advanced solid tumors
Abstract:	Background: S-1 is a novel oral agent combining the 5-fluorouracil (FU) prodrug tegafur with gimeracil and oteracil, which inhibit 5-FU degradation by dihydropyrimidine dehydrogenase and phosphorylation within the gastrointestinal tract, respectively. The study was designed to identify the maximum tolerable dose and the dose-limiting toxicities of two schedules of S-1 combined with oxaliplatin and bevacizumab, in advanced solid tumor patients. Methods: Schedule A: S-1 was administered orally at 20 mg/m2 twice daily for 14 consecutive days, escalated by 5 mg/m2, with fixed-dose intravenous bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 of each 3-week cycle. Schedule B: S-1 was administered at 25 mg/m2 twice daily for 7 consecutive days, escalated by 5 mg/m2, with fixed-dose intravenous bevacizumab 5 mg/kg and oxaliplatin 85 mg/m2 on day 1 of each 2-week cycle. Results: The maximum tolerated dose and recommended phase II dose of S-1 was 25 mg/m2 twice daily for 14 days for schedule A and 35 mg/m2 twice daily for 7 days for schedule B. The most common dose-limiting toxicities were grade 3 diarrhea. Both regimens were well tolerated. No pharmacokinetic interactions between oxaliplatin and S-1 components were observed. Conclusions: S-1, oxaliplatin and bevacizumab can be administered with acceptable safety and tolerability and without evidence of pharmacokinetic interactions. Copyright © 2011 S. Karger AG.
Keywords:	adult; clinical article; aged; middle aged; constipation; fatigue; neutropenia; bevacizumab; fluorouracil; advanced cancer; area under the curve; cancer combination chemotherapy; diarrhea; side effect; solid tumor; neoplasms; multiple cycle treatment; anemia; leukopenia; lung non small cell cancer; stomatitis; thrombocytopenia; antineoplastic combined chemotherapy protocols; dehydration; peripheral neuropathy; weight reduction; abdominal pain; drug dose escalation; colorectal tumor; liver tumor; nausea and vomiting; pancreas adenocarcinoma; hyperbilirubinemia; maximum plasma concentration; time to maximum plasma concentration; maximum tolerated dose; phase 1 clinical trial; drug half life; drug combinations; oxaliplatin; administration, oral; organoplatinum compounds; proteinuria; hypersensitivity reaction; esophagus tumor; head and neck tumor; biliary tract tumor; rectum hemorrhage; antidiarrheal agent; tegafur; advanced solid tumor; pharmacokinetic interaction; s-1; gimeracil plus oteracil potassium plus tegafur; antibodies, monoclonal, humanized; oxonic acid
Journal Title:	Oncology
Volume:	81
Issue:	2
ISSN:	0030-2414
Publisher:	S. Karger AG
Date Published:	2011-10-01
Start Page:	65
End Page:	72
Language:	English
DOI:	10.1159/000331010
PROVIDER:	scopus
PUBMED:	21968463
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-80054928149&partnerID=40&md5=792953d4baa2cadf648cd80016f4c228
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 9 December 2011" - "CODEN: ONCOB" - "Source: Scopus"

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