title: Phase-I-study of four different schedules of pemetrexed, gemcitabine and cisplatin in patients with locally advanced or metastatic solid tumours.
abstract: This non-randomised Phase-I-study determined recommended dose (RD) and dose-limiting toxicities (DLTs) of four different schedules combining pemetrexed (P), gemcitabine (G) and cisplatin (C). Patients 18 years with locally advanced/metastatic cancer were enrolled. Doses were escalated for one 21-d (q3w; PGC d1, G d8) and three 28-d schedules (q4wA: PG d1, GC d15; q4wB: GC d1, PC d15; q4wC: PGC d1+15). Starting doses were P 400/500 mg/m(2) (q3w/q4w), G 800 mg/m(2) and C 40 mg/m(2). Sixty patients were enroled (n=12/14/30/4 for q3w/q4wA/q4wB/q4wC). Common cancers included head and neck (n=19), prostate (n=7), sarcoma (n=5) and stomach (n=5). Thirteen patients experienced DLTs, most frequently fatigue (n=4) and neutropenia (n=3). Schedule q4wB reached the highest doses (P 600 mg/m(2) d15; G 1250 mg/m(2) d1; C 70 mg/m(2)d1+15). There were no CRs, 11 PRs and 25 SDs (n=47). The PGC-combination was feasible. The recommended schedule for subsequent studies would be 1250 mg/m(2) G and 60 mg/m(2) C on d1, followed by 500 mg/m(2) P and 60 mg/m(2) C on d15.
authors.affiliation: St Georg Hospital III, Department of Medicine, Hamburg, Germany. Hanauske.ind-synergen@t-online.de
authors.forename: Axel-R
authors.initials: AR
authors.lastname: Hanauske
authors.forename: Corinna
authors.initials: C
authors.lastname: Endler
authors.forename: Tobias
authors.initials: T
authors.lastname: Graefe
authors.forename: Jochen
authors.initials: J
authors.lastname: Fleeth
authors.forename: Jobst
authors.initials: J
authors.lastname: von Scheel
authors.forename: Frank E
authors.initials: FE
authors.lastname: Lüdtke
authors.forename: Sigrun
authors.initials: S
authors.lastname: Müller-Hagen
authors.forename: Henrik
authors.initials: H
authors.lastname: Depenbrock
authors.forename: Ute
authors.initials: U
authors.lastname: Ohnmacht
authors.forename: Claus
authors.initials: C
authors.lastname: Bolling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D002945:Cisplatin; D000093542:Gemcitabine