Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer: JCOG 9515.
To evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin (BLM), OK-432 (a pulverized product of heat-killed Streptococcus pyogenes) or cisplatin plus etoposide (PE) for the management of malignant pleural effusion (MPE) in previously untreated non-small cell lung cancer. Eligible patients were randomized to the BLM arm: BLM 1mg/kg (maximum 60mg/body), the OK-432 arm: OK-432 0.2 Klinische Einheit units (KE)/kg (maximum 10KE/body), or the PE arm: cisplatin (80mg/m(2)) and etoposide (80mg/m(2)). Pleural response was evaluated every 4 weeks according to the study-specific criteria. All responders received systemic chemotherapy consisting of PE every 3-4 weeks for two or more courses. Pleural progression-free survival (PPFS) was defined as the time from randomization to the first observation of pleural progression or death due to any cause. The primary endpoint was the 4-week PPFS rate. Of 105 patients enrolled, 102 were assessed for response. The 4-week PPFS rate for the BLM arm was 68.6%, 75.8% for the OK-432 arm, and 70.6% for PE arm. Median survival time (MST) for the BLM arm was 32.1 weeks, 48.1 weeks for the OK-432 arm, and 45.7 weeks for the PE arm. However, the outcomes did not differ significantly between groups. Toxicity was tolerable in all arms except for one treatment-related death due to interstitial pneumonia induced by BLM. We will select intrapleural treatment using OK-432 in the management of MPE in NSCLC for further investigation because it had the highest 4-week PPFS rate.
Yoshida
Kimihide
K
Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. 105197@aichi-cc-jp
Sugiura
Takahiko
T
Takifuji
Nobuhide
N
Kawahara
Masaaki
M
Matsui
Kaoru
K
Kudoh
Shinzoh
S
Takada
Minoru
M
Fukuoka
Masahiro
M
Ariyoshi
Yutaka
Y
Fukuda
Haruhiko
H
Saijo
Nagahiro
N
D000328:Adult; D000368:Aged; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002945:Cisplatin; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010844:Picibanil / Q000009:adverse effects / Q000627:therapeutic use; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000473:pathology*; D015996:Survival Rate
D001761:Bleomycin; D010844:Picibanil; D002945:Cisplatin