A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma

Our plain-English summary of A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma, by V. Rusch, L. Saltz, E. Venkatraman, et al (Journal of Clinical Oncology, 1994).

The study

• Authors: V. Rusch, L. Saltz, E. Venkatraman, R. Ginsberg, P. McCormack, M. Burt, M. Markman, D. Kelsen
• Journal: Journal of Clinical Oncology
• Published: 1994;12(6):1156-63
• Cited by: 138 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy.

Patients And Methods: Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first.

Results: Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients).

Conclusion: This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control.

In plain English

This New York phase II trial tested the feasibility of combined treatment for malignant pleural mesothelioma. The plan was lung-sparing surgery (pleurectomy/decortication), then cisplatin and mitomycin placed in the chest cavity, then the same drugs intravenously 3 to 5 weeks later. Of 36 patients entered (October 1989 to March 1992), 28 had this surgery and chest-cavity chemotherapy; 8 had tumor that could not be removed this way. Of the 27 who became candidates for intravenous chemotherapy, 16 (59%) recalled asbestos exposure. One patient died after surgery; another needed dialysis for kidney failure. The 23 given intravenous chemotherapy got a median of 80% of planned cisplatin and 87% of planned mitomycin. Among the 27, survival was 69% at 1 year (95% confidence interval 54% to 90%) and 40% at 2 years (95% confidence interval 25% to 65%); median survival was 18.3 months. Patients with pure epithelial tumors survived significantly longer. Of 20 first relapses, 16 were local only. The authors concluded the regimen was feasible but should stay within research protocols because of potential toxicity, and did not give most patients long-term local control.

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: Phase II (feasibility) clinical trial of a combined surgery and chemotherapy regimen; no comparison group
• Who was studied: 36 patients with biopsy-proven, previously untreated malignant pleural mesothelioma, entered October 1989 to March 1992 at Memorial Sloan-Kettering Cancer Center, New York. 27 of them (24 men, 3 women; median age 62, range 46 to 75) were candidates for systemic chemotherapy.
• Exposure: The study examined a treatment, not asbestos exposure. The regimen was pleurectomy/decortication, then intrapleural cisplatin (100 mg/m2 for the first 17 patients, lowered to 75 mg/m2 for the other 11) with mitomycin 8 mg/m2, then systemic cisplatin and mitomycin. Of the 27 candidates for systemic chemotherapy, 16 recalled a history of asbestos exposure. No fiber types are given.
• Main results:
  • Of the 36 patients entered, 8 were removed from the study in the operating room because their tumor could not be removed by pleurectomy/decortication. All 28 who had the operation received intrapleural chemotherapy.
  • There was one postoperative death. Two patients developed renal insufficiency after intrapleural chemotherapy, and one of them required dialysis.
  • The 23 patients who received systemic chemotherapy got a median of 80% of the planned total cisplatin dose (range 25% to 100%) and 87% of the planned total mitomycin dose (range 50% to 100%).
  • In the 27 candidates for systemic chemotherapy, overall survival was 69% at 1 year (95% confidence interval 54% to 90%) and 40% at 2 years (95% confidence interval 25% to 65%).
  • In the 27 candidates, median overall survival was 18.3 months (range 1 to 44.7) and median progression-free survival was 13.6 months.
  • Overall survival differed significantly by cell type (P = .0375). Patients with pure epithelial tumors survived longer than those with mixed or fibrosarcomatous mesothelioma.
  • Among 20 patients with a first relapse, 16 (80%) relapsed locally only, 1 (5%) both locally and at a distance, and 3 (15%) at a distance only.
• The authors' conclusion: The authors concluded that the regimen was feasible but should not be used outside a protocol setting because of its potential toxicity. They also concluded that one postoperative intrapleural dose followed by systemic chemotherapy did not give long-term local control for most patients.
• Limitations the authors state:
  • The authors cautioned that the effects of patient characteristics such as TNM stage on survival must be interpreted carefully in a small nonrandomized trial.
  • The authors noted that the study was not designed to detect survival differences among small subsets of patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleurectomy/Decortication (P/D), Chemotherapy, Pleural Mesothelioma, Surgical Resection, Biopsy, Cisplatin, Overall Survival, Median Survival.

Related studies

• Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies — V.W. Rusch, D. Niedzwiecki, et al. (1992)
• Pleurectomy/decortication and hyperthermic intrapleural chemotherapy for malignant pleural mesothelioma: initial experience — M. Migliore, D. Calvo, et al. (2015)
• Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy, and systemic chemotherapy in patients with malignant pleural mesothelioma: a 10-year experience — L. Lang-Lazdunski, A. Bille, et al. (2015)
• A Phase II Trial of Nivolumab With Chemotherapy Followed by Maintenance Nivolumab in Patients With Pleural Mesothelioma After Surgery: The NICITA Study Protocol — R. Shah, L.V. Klotz, et al. (2021)
• A feasibility study of induction pemetrexed plus cisplatin followed by pleurectomy/decortication aimed at macroscopic complete resection for malignant pleural mesothelioma — M. Shimokawa, S. Hasegawa, et al. (2013)
• 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)

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