Phase-I-study of four different schedules of pemetrexed, gemcitabine and cisplatin in patients with locally advanced or metastatic solid tumours

• Published in: European journal of cancer (1990) 2008-11, Vol.44 (16), p.2444-2452
• Main Authors: Hanauske, Axel-R, Endler, Corinna, Graefe, Tobias, Fleeth, Jochen, Scheel, Jobst von, Lüdtke, Frank E, Müller-Hagen, Sigrun, Depenbrock, Henrik, Ohnmacht, Ute, Bolling, Claus
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cisplatin - adverse effects; Combination treatment; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Feasibility Studies; Female; Gemcitabine; Glutamates - administration & dosage; Glutamates - adverse effects; Guanine - administration & dosage; Guanine - adverse effects; Guanine - analogs & derivatives; Hematology, Oncology and Palliative Medicine; Humans; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - drug therapy; Pemetrexed; Pharmacology. Drug treatments; Phase-I-study; Treatment Outcome; Tumors; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2008.08.002

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/m2 (q3w/q4w), G 800 mg/m2 and C 40 mg/m2 . 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/m2 d15; G 1250 mg/m2 d1; C 70 mg/m2 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/m2 G and 60 mg/m2 C on d1, followed by 500 mg/m2 P and 60 mg/m2 C on d15.