Phase I/II trial of biweekly docetaxel and cisplatin with concurrent thoracic radiation for stage III non-small-cell lung cancer.
OBJECTIVE
We conducted phase I and II studies of biweekly docetaxel and cisplatin with concurrent radiotherapy, followed by consolidation chemotherapy with the same drugs in patients with locally advanced, unresectable non-small-cell lung cancer (NSCLC). Our objectives were to define the maximum-tolerated dose and dose-limiting toxicity (DLT) in the phase I study, and to determine the response rate, toxicity, and survival rate at the recommended dose (RD) in the phase II study.


METHODS
Patients with unresectable stage IIIA and IIIB NSCLC were studied. Six to eight cycles of docetaxel and cisplatin were administered at 2-week intervals. In the phase I study, patients received four dose levels: level 1, docetaxel/cisplatin=30/40 mg/m2; level 2, 35/40; level 3, 40/40; and level 4, 45/40. Radiotherapy was delivered at a rate of 2 Gy per fraction/day up to a total dose of 60 Gy over the course of 6 weeks, during the first three cycles of chemotherapy.


RESULTS
DLT comprised neutropenia at level 4 in the phase I study (n=15), and level 3 was considered the RD. In the phase II study (n=46), two patients had a complete response (4.3%) and 34 had a partial response (73.9%), for an overall response rate of 78.2% [95% CI (66.3-90.2%)]. The survival rate was 69.1% at 1 year and 39.6% at 2 years, with a median survival time of 19.1 months. Leukopenia, neutropenia, anemia, and radiation esophagitis were the most common toxic reactions, with Grade > or = 3 reactions occurring at rates of 77, 70, 17, and 8%, respectively.


CONCLUSIONS
Biweekly docetaxel and cisplatin with concurrent RT was active and well tolerated in patients with unresectable stage III NSCLC.
Iwasaki
Yoshinobu
Y
Division of Pulmonary Medicine, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji, Kamigyo-ku, 602, Kyoto, Japan. yiwasaki@koto.kpu-m.ac.jp
Ohsugi
Shuji
S
Natsuhara
Atsushi
A
Tsubokura
Takuji
T
Harada
Hidehiko
H
Ueda
Mikio
M
Arimoto
Taichiro
T
Hara
Hiroshi
H
Yamada
Tadaaki
T
Takesako
Toshiyuki
T
Kohno
Kenji
K
Hosogi
Shigekuni
S
Nakanishi
Masaki
M
Marunaka
Yoshinori
Y
Nishimura
Tsunehiko
T
D000328:Adult; D000368:Aged; 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 / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects; D000077143:Docetaxel; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D004941:Esophagitis / Q000209:etiology; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000209:etiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin