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.