A dose-escalation study of pemetrexed and docetaxel in non-small-cell lung cancer.
A phase I study was conducted to determine the maximum tolerated doses (MTD) and the dose-limiting toxicities (DLT) of pemetrexed and docetaxel in patients with advanced unresectable or metastatic non-small-cell lung cancer (NSCLC). Patients were treated with escalating doses of pemetrexed (400-600 mg/m(2) as a 10-min intravenous infusion) and docetaxel (65-85 mg/m(2) as a 1-h intravenous infusion) on day 1, every 3 weeks. An expanded accrual at the level of the recommended dose (RD) had been scheduled. Forty-two patients with metastatic NSCLC were enrolled in the phase I study and 20 additional patients at the RD level. The MTD could not be reached even at the doses of 550 and 85 mg/m(2) for pemetrexed and docetaxel, respectively, which are higher than the recommended dose for each drug given as a single agent. Therefore, the RD was defined at 500 mg/m(2) pemetrexed and 75 mg/m(2) docetaxel. Among the 164 administered chemotherapy cycles (phase I part), there were three episodes of febrile neutropenia whereas 13 (7.9%) and 11 (6.7%) cycles were complicated with grade III and IV neutropenia, respectively. Three patients developed grade III/IV thrombocytopenia. Non-hematologic toxicity was mild with grade III fatigue occurring in three (6.7%) patients. There was no toxic death. The favorable toxicity profile of the regimen was confirmed in patients treated at the RD level. Overall, one complete (CR) and 13 partial responses (PR) (overall response rate = 23; 95% C.I:12.4-33.5%] were documented. The combination of pemetrexed and docetaxel seems to be an effective regimen in NSCLC with acceptable and manageable toxicity, which merits further investigation.
Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece. georgsec@med.uoc.gr
Athanasios
A
Kotsakis
Sophia
S
Agelaki
Nikolaos
N
Vardakis
George
G
Stathopoulos
Lambros
L
Vamvakas
Antonia
A
Kalykaki
Nikolaos
N
Kentepozidis
Emmanouel
E
Kontopodis
Georgia
G
Sfakiotaki
Dimitris
D
Mavroudis
Vassilis
V
Georgoulias
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D005971:Glutamates; D043823:Taxoids; D050257:Tubulin Modulators; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine