RESUMO
The objectives of this phase I study were to determine the maximum tolerated dose (MTD), recommended phase II dose (RD), antitumor activity, safety, and pharmacokinetics of pemetrexed-paclitaxel combination. Patients (N = 95) with advanced solid tumors were assigned to three schedules (21-day cycles [q21d]). Starting doses for each schedule of pemetrexed and paclitaxel, respectively, were: (S1) 400 and 135 mg/m(2) on d1; (S2) 400 mg/m(2) d1 and 40 mg/m(2) d1 and d8; S3) 400 mg/m(2) d8 and 30 mg/m(2) d1 and d8. MTD was 500/135 mg/m(2) (S1), 400/40 mg/m(2) (S2), and 500/120 mg/m(2) (S3). Most common dose limiting toxicities were febrile neutropenia, fatigue, and neuromotor toxicities. Most common toxicity was grade 3/4 lymphopenia. Four patients had partial response, 43 patients had stable disease. The RD determined was pemetrexed 500 mg/m(2) (d8) and paclitaxel 90 mg/m(2) (d1 and d8), q21d. The combination was well tolerated and showed efficacy in thyroid carcinoma and mesothelioma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dose Máxima Tolerável , Neoplasias/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Masculino , Mesotelioma/tratamento farmacológico , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Pemetrexede , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto JovemRESUMO
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.
