Phase I study of cisplatin analogue nedaplatin, paclitaxel, and thoracic radiotherapy for unresectable stage III non-small cell lung cancer.
BACKGROUND
The standard treatment of unresectable stage III non-small cell lung cancer is concurrent chemoradiotherapy in patients in good general condition, but where the optimal chemotherapeutic regimen has not been determined.


METHODS
Patients with unresectable stage III non-small cell lung cancer received nedaplatin (80 mg/m2) and paclitaxel on day 1 every 4 weeks for 3-4 cycles and concurrent thoracic radiotherapy (60 Gy/30 fractions for 6 weeks) starting on day 1. The dose of paclitaxel was escalated from 120 mg/m2 in level 1, 135 mg/m2 in level 2 to 150 mg/m2 in level 3.


RESULTS
A total of 18 patients (14 males and 4 females, with a median age of 62.5 years) were evaluated in this study. Full cycles of chemotherapy were administered in 83% of patients in level 1, and in 50% of patients in levels 2 and 3. No more than 50% of patients developed grade 4 neutropenia. Transient grade 3 esophagitis and infection were noted in one patient, and unacceptable pneumonitis was noted in three (17%) patients, two of whom died of the toxicity. Dose-limiting toxicity (DLT), evaluated in 15 patients, noted in one of the six patients in level 1, three of the six patients in level 2 and one of the three patients in level 3. One DLT at level 2 developed later as radiation pneumonitis. Thus, the maximum tolerated dose was determined to be level 1. The overall response rate (95% confidence interval) was 67% (41-87%) with 12 partial responses.


CONCLUSIONS
The doses of paclitaxel and nedaplatin could not be escalated as a result of severe pulmonary toxicity.
Sekine
Ikuo
I
Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. isekine@ncc.go.jp
Sumi
Minako
M
Ito
Yoshinori
Y
Kato
Terufumi
T
Fujisaka
Yasuhito
Y
Nokihara
Hiroshi
H
Yamamoto
Noboru
N
Kunitoh
Hideo
H
Ohe
Yuichiro
Y
Tamura
Tomohide
T
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; C053989:nedaplatin; D017239:Paclitaxel