Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial

Our plain-English summary of Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial, by V.W. Rusch, R. Figlin, D. Godwin, et al (Journal of Clinical Oncology, 1991).

The study

• Authors: V.W. Rusch, R. Figlin, D. Godwin, S. Piantadosi
• Journal: Journal of Clinical Oncology
• Published: 1991;9(2):313-9
• Cited by: 95 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural effusions are a common and significant problem in patients with advanced malignancies. Pleurodesis with tetracycline or other sclerosing agents is the usual treatment for malignant pleural effusions. In contrast to this approach, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the effusion. Intracavitary cisplatin-based chemotherapy, which is cytotoxic rather than sclerosing, has proven safe and effective via the intraperitoneal route in ovarian cancer and malignant mesothelioma. There has been little previous experience, however, with intrapleural cisplatin-based chemotherapy. As part of a planned series of trials in malignant mesothelioma, the Lung Cancer Study Group first evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors. From April 1986 to November 1987, 46 patients with cytologically proven, symptomatic, and previously untreated malignant pleural effusions were entered on study. A single dose of cisplatin 100 mg/m2 plus cytarabine 1,200 mg was instilled into the pleural space via a chest tube, which was then immediately removed. Patients were evaluated for toxicity and response at 24 hours; 1, 2, and 3 weeks; and then monthly. No recurrence of the effusion was considered a complete response (CR). Partial response (PR) was defined as a 75% or greater decrease in the amount of the effusion on serial chest radiographs. One patient experienced reversible grade 4 renal toxicity, four patients had grade 3 hematologic toxicity, and five patients had grade 3 cardiopulmonary toxicity. The overall response rate (CR plus PR) at 3 weeks was 49% (18 of 37 patients). The median length of response was 9 months for a CR and 5.1 months for a PR. The outcome of this trial was sufficiently encouraging that this regimen has been incorporated into subsequent trials for malignant pleural mesothelioma.

In plain English

This trial did not study asbestos exposure. From April 1986 to November 1987, 46 patients with cancer-related fluid around the lung (malignant pleural effusions) were enrolled; most had lung cancer, two malignant mesothelioma. Most treated patients received one dose of cisplatin and cytarabine, chemotherapy drugs placed into the chest through a tube; four had a second course, without response. Nine patients died of progressive disease within three weeks. At three weeks, 18 patients responded (6 completely; 12 partially, meaning at least 75% less fluid): 39% of all 46 (95% confidence interval 25% to 55%) and 49% of the 37 assessable (32% to 66%). Median response lasted 9 months for complete and 5.1 months for partial responses. One patient needed short-term dialysis for kidney failure. By last follow-up, 40 of 46 had died; median survival was 5.7 months. The authors concluded the drugs were safe and may help treat the cancer while controlling the fluid. Response rates and durations were no better than those historically reported for tetracycline, though the authors called this comparison difficult because those studies' response criteria and follow-up varied.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Multi-institution phase II treatment trial (LCSG 861), with all patients receiving the same intrapleural chemotherapy; the first of a planned series of studies aimed mainly at malignant mesothelioma
• Who was studied: 46 patients (20 men, 26 women; average age 63, range 39 to 88) with symptomatic, cytologically proven, previously untreated malignant pleural effusions from various tumors, entered April 1986 to November 1987 at Lung Cancer Study Group institutions. Primary sites: lung 24, breast 8, ovary 5, pleura 2, esophagus 1, pancreas 1, stomach 1, unknown 4. Two patients had malignant mesothelioma.
• Exposure: No asbestos exposure was studied. The intervention was a single dose of cisplatin 100 mg/m2 plus cytarabine 1,200 mg instilled into the pleural space through a chest tube or catheter for 4 hours. Patients whose effusion stabilized were to receive a second identical dose.
• Main results:
  • Among all 46 patients entered, 6 had a complete response and 12 a partial response at 3 weeks, an overall response rate of 39% (18 of 46; 95% confidence interval, 25% to 55%)
  • Among the 37 patients assessable at 3 weeks, the response rate was 49% (95% confidence interval, 32% to 66%)
  • Four patients received a second course of intrapleural chemotherapy; none of them had an objective response
  • Nine patients died of progressive disease in the first 3 weeks and could not be assessed for response
  • Median length of response was 9 months for the 6 complete responders and 5.1 months for the 12 partial responders
  • 43 of 46 patients were assessable for toxicity. The only life-threatening toxicity was renal failure requiring short-term dialysis in one elderly patient who had not received adequate hydration.
  • Among the 43 assessable patients, 4 (9%) had grade 3 hematologic toxicity
  • Among the 43 assessable patients, 5 (11%) had grade 3 cardiopulmonary symptoms
  • Among the 43 assessable patients, 38 (88%) had grade 1 to 2 nausea and vomiting
  • At last follow-up, 14 months after the study closed, 40 of the 46 patients had died
  • Median survival was 5.7 months
  • The authors stated that response rates and durations were not superior to those historically reported for intrapleural tetracycline
• The authors' conclusion: The authors concluded that intrapleural cisplatin and cytarabine are safe and may play a role in treating the underlying malignancy as well as controlling the effusion
• Limitations the authors state:
  • Cardiopulmonary toxicity may have been overestimated because it is hard to measure in patients with advanced disease who are short of breath for many reasons
  • Drug levels in the pleural fluid and blood could not be measured in this multi-institution study
  • Comparison with tetracycline studies is difficult because those studies used variable and sometimes poorly defined response criteria and follow-up

Topics

Medical terms in this study, explained in our Lexicon: Cisplatin, Pleural Effusion, Lung Cancer, Pleurodesis, Chemotherapy, Ovarian Cancer, Mesothelioma, Chest X-Ray.

Related studies

• The efficacy of pemetrexed and bevacizumab intrapleural injection for malignant pleural mesothelioma-mediated malignant pleural effusion — D. Chen, X. Li, et al. (2014)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)
• Intrapleural recombinant IL-2 in passive immunotherapy for malignant pleural effusion — P. Astoul, J.R. Viallat, et al. (1993)
• Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion — H. Sakaguchi, H. Ishida, et al. (2017)
• Optimal management of malignant mesothelioma after subtotal pleurectomy: revisiting the role of intrapleural chemotherapy and postoperative radiation — E.R. Sauter, C. Langer, et al. (1995)
• Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies — V.W. Rusch, D. Niedzwiecki, et al. (1992)

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