title: Phase I dose escalation study of gemcitabine plus irinotecan in advanced solid tumors.
abstract: OBJECTIVE
  To determine the maximally tolerated dose (MTD), recommended phase II dose (RPTD) and toxicity profile of gemcitabine plus irinotecan combination.
  
  
  METHODS
  Thirty-nine evaluable patients with advanced solid tumors were treated with gemcitabine (Gem) and irinotecan (Iri) on days 1, 8 and 15 of a 28-day cycle. Dose levels included Gem/Iri 700/50, 900/50, 900/75, 500/50 mg/m(2) respectively. Dose-limiting toxicity (DLT) was assessed during cycle one; toxicity evaluation was closely monitored throughout the course of treatment. Treatment continued until disease progression or unacceptable toxicity.
  
  
  RESULTS
  DLTs primarily consisted of grade > or = 3 thrombocytopenia lasting > or = 4 days often accompanied by grade > or = 3 neutropenia. Other grade > or = 3 toxicities included vomiting, diarrhea, fatigue and elevated alkaline phosphatase. Three patients had a partial response. Stable disease as best response was seen in 16 patients, ranging from 2-18 months.
  
  
  CONCLUSIONS
  The MTD/RPTD is gemcitabine 500 mg/m(2) plus irinotecan 50 mg/m(2) on days 1, 8 and 15 of a 28-day cycle. Given the toxicity profile and negative results of phase III studies, no further testing of this treatment combination is recommended.
authors.affiliation: Duke University Medical Center, Durham, NC, 27710, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dugan
authors.forename: Roxanne
authors.initials: R
authors.lastname: Truax
authors.forename: Kellen L
authors.initials: KL
authors.lastname: Meadows
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Blobe
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: Nishan H
authors.initials: NH
authors.lastname: Fernando
authors.forename: Jon P
authors.initials: JP
authors.lastname: Gockerman
authors.forename: William P
authors.initials: WP
authors.lastname: Petros
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016022:Case-Control Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine