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
Introduction
Malignant pleural effusion (MPE) is a significant problem in the treatment of patients with advanced malignancies and is a major cause of poor prognosis [1]. The most widely used therapy for MPE is tube drainage with intrapleural instillation of sclerosing agents to prevent fluid reaccumulation [2].
Despite many reported trials of chemical pleurodesis, there has been no agreement as to the optimal treatment protocol for MPE [3], [4], [5]. The variety of response rates of individual agents among those studies has resulted from heterogeneous patient populations and differences in treatment procedures and response criteria [2], [3], [6]. To resolve these problems, we conducted a randomized phase II trial in which patient selection was limited to previously untreated patients with MPE due to non-small cell lung cancer (NSCLC) and, in view of adequate estimation of the efficacy of each intrapleural therapy regimen, single instillation of chemical agents and uncomplicated study-specific response criteria were applied. In this study, to select the most promising regimen for intrapleural therapy consisting of sclerosing or chemotherapeutic agents, we chose three regimens—BLM, OK-432 and cisplatin plus etoposide (PE). BLM was chosen because it is one of the most frequently used agents and is considered to have high efficacy, low toxicity and high availability [3], [5], [7], [8]. OK-432 (a preparation of Streptococcus pyogenes, type A3, Chugai Pharmaceutical Co., Tokyo) has been used as an anti-tumor immunomodulator for lung cancer [9], [10] and is reported to give superior responses for MPE compared to mitomycin C [11] and BLM [12]. At the beginning of this study, PE regimens were considered one of the standard combination chemotherapy regimens for NSCLC, and a phase II trial using this regimen for intrapleural therapy suggested potential survival benefit as well as local control effects [13].
Section snippets
Patient selection
The eligibility criteria were as follows: cytologically or histologically proven malignant pleural effusion associated with newly diagnosed NSCLC; no prior chemotherapy, thoracic radiotherapy or thoracic surgery; age of 75 years or less; Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–2 after tube thoracostomy; full lung reexpansion after tube thoracostomy; adequate bone marrow reserve (WBC count ≥4000 μL−1, hemoglobin ≥9.5 g/dL, and platelet count ≥100,000 μL−1), and liver
Patients
From May 1996 to August 1999, 105 patients were enrolled onto this study from the 21 participating institutions. The clinical characteristics of the patients are listed in Table 1. Three patients were later found to be ineligible (one patient per group): one had malignant pleural effusion secondary to colon cancer; one had no reexpansion of the affected lung after tube drainage; and one had poor renal function. Thus, 102 patients were assessable for response and survival. Four patients did not
Discussion
To date, numerous chemical agents for treatment of MPE have been studied. These were antibiotics, antineoplastic agents, biological response modifiers (BRMs) and others that showed varied degrees of chemical sclerosis. Among them, BLM and talc are most frequently used for the management of MPE [5], [7], [17], [18]. BLM is an antineoplastic antibiotic used in sclerotherapy with a success rate of 63–85% [7], [8], [18], [19], [20], [21]. Talc applied as either slurry or poudrage is superior to
Conflict of interest
None declared.
Acknowledgements
We are indebted to Ms. M. Imai and Dr. M. Niimi for data management and to Dr. N. Ishizuka for statistical analysis. We thank all of the investigators who contributed to study development and patient enrollment.
Supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan.
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2017, Archivos de BronconeumologiaA propensity score-matched comparison of the efficacies of OK-432 and talc slurry for pleurodesis for malignant pleural effusion induced by lung adenocarcinoma
2016, Respiratory InvestigationCitation Excerpt :The efficacy of OK-432 for pleurodesis was evaluated in a study involving East Asian patients with lung cancer [6,9–11], breast cancer [8], and pneumothorax [7]. Comparative studies reported a higher success rate by using OK-432 than by using bleomycin, mitomycin-C, or cisplatin/etoposide [9–11]. However, no previous studies have directly compared the sclerosant effects of OK-432 and talc-s.