Dose-escalation study of thoracic radiotherapy in combination with pemetrexed plus Cisplatin followed by pemetrexed consolidation therapy in Japanese patients with locally advanced nonsquamous non-small-cell lung cancer.
BACKGROUND
Pemetrexed has radiosensitizing potential when evaluated in vitro in combination with platinum-containing compounds and radiation. We determined the recommended dose (RD) of thoracic radiotherapy (TRT) with a concurrent chemotherapy combination of pemetrexed and cisplatin in Japanese patients with nonsquamous non-small-cell lung cancer (NSCLC).


METHODS
Eligible patients were histologically confirmed as having locally advanced nonsquamous NSCLC. Study treatment consisted of 2 phases: concurrent chemoradiation and consolidation. In the concurrent chemoradiation phase, all patients received pemetrexed 500 mg/m(2) plus cisplatin 75 mg/m(2) on day 1 of a 21-day interval for 3 cycles. The first 6 patients were given 60 Gy concurrently at level 1 dose (L1D). If dose-limiting toxicity (DLT) occurred in < 2 patients at L1D, radiation was escalated to 66 Gy (level 2 dose [L2D]).


RESULTS
Eighteen patients were treated and completed chemoradiotherapy; 12 completed the consolidation phase. In the concurrent chemoradiation phase, 1 patient experienced 2 DLTs [grade 3 anorexia and diarrhea] at L1D. Because no DLT was observed at L2D, it was determined to be the RD. Common toxicities ≥grade 3 were neutropenia and leukopenia. At L1D, 1 patient each experienced grade 2 and grade 3 pneumonitis, and 2 patients experienced grade 2 esophagitis. Six patients experienced grade 2 pneumonitis and 3 patients experienced grade 2 esophagitis at L2D. Fifteen patients achieved partial response (PR), 2 had stable disease (SD), and 1 had progressive disease (PD).


CONCLUSIONS
Expected toxicities from concurrent chemoradiation were not worsened with concurrent TRT at a total dose of 66 Gy combined with pemetrexed in Japanese patients with locally advanced (LA) nonsquamous NSCLC.
Division of Thoracic Oncology, National Cancer Centre Hospital East, Chiba, Japan. siniho@east.ncc.go.jp
Seiji
S
Niho
Kaoru
K
Kubota
Keiji
K
Nihei
Ikuo
I
Sekine
Minako
M
Sumi
Risa
R
Sekiguchi
Jumpei
J
Funai
Sotaro
S
Enatsu
Yuichiro
Y
Ohe
Tomohide
T
Tamura
D000328:Adult; D000368:Aged; D000855:Anorexia / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage; D060830:Consolidation Chemotherapy; D003967:Diarrhea / Q000209:etiology; D004941:Esophagitis / Q000209:etiology; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007564:Japan; D007970:Leukopenia / Q000209:etiology; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed; D011014:Pneumonia / Q000209:etiology; D011879:Radiotherapy Dosage; D016896:Treatment Outcome
D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin