title: Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine.
abstract: OBJECTIVE
  To assess the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of orally administered irinotecan in the semi-solid matrix (SSM) formulation, both as a single agent and in sequential combination with capecitabine, in patients with advanced solid tumors.
  
  
  METHODS
  Forty-three patients were treated with irinotecan given as a single oral daily dose on days 1-5 every three weeks. An additional forty patients were treated with sequential oral irinotecan given daily on days 1-5 followed by capecitabine given orally as a divided dose twice daily on days 6-14 of each three week cycle.
  
  
  RESULTS
  The MTD of single-agent oral irinotecan was estimated to be 60 mg/m(2)/day, and DLT included diarrhea, nausea, and neutropenia. In an initial group of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, the MTD of sequential oral irinotecan/capecitabine was estimated to be 40/1600 mg/m(2)/day with DLT of delayed diarrhea. In a subsequent group of patients with ECOG PS of 0 or 1, the MTD for the sequential combination was 50/2000 mg/m(2)/day. The most common adverse events were fatigue, diarrhea, nausea/vomiting and dehydration. Pharmacokinetic (PK) evaluation showed that oral irinotecan was rapidly absorbed and effectively converted to the active metabolite, SN-38, achieving approximately 50% of the SN-38 systemic exposure resulting from an equivalent IV dose.
  
  
  CONCLUSIONS
  Oral irinotecan can be safely administered as a single agent or in sequential combination with capecitabine. The efficacy of oral irinotecan should be explored further as a potentially convenient alternative to IV chemotherapy.
authors.affiliation: Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232-6307, USA. Laura.goff@vanderbilt.edu
authors.forename: Laura W
authors.initials: LW
authors.lastname: Goff
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: Patricia M
authors.initials: PM
authors.lastname: LoRusso
authors.forename: Antoinette R
authors.initials: AR
authors.lastname: Tan
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Berlin
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Denis
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Benner
authors.forename: Donghua
authors.initials: D
authors.lastname: Yin
authors.forename: Mace L
authors.initials: ML
authors.lastname: Rothenberg
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin