Intracavitary Therapeutics for Pleural Malignancies

Our plain-English summary of Intracavitary Therapeutics for Pleural Malignancies, by V. Murthy, K. Mangalick, D.H. Sterman (Clinics in Chest Medicine, 2018).

The study

• Authors: V. Murthy, K. Mangalick, D.H. Sterman
• Journal: Clinics in Chest Medicine
• Published: 2018;39(1):195-209
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pleural malignancies remain a serious therapeutic challenge, and are frequently refractory to standard treatment; however, they have the advantage of occurring in an enclosed cavity readily accessible for examination, biopsy, and serial sampling. Novel therapeutics can be administered via intracavitary delivery to maximize efficacy by targeting the site of involvement and potentially mitigating the adverse effects of systemic therapies. The easy accessibility of the pleural space lends itself well to repeated sampling and analysis to determine efficacy and toxicity of a given treatment paradigm. These factors support the rationale for delivery of novel therapeutics directly into the pleural space.

Copyright © 2017 Elsevier Inc. All rights reserved.

In plain English

This article reviewed cancer treatments delivered directly into the pleural space around the lungs. It covered pleural malignancies, mainly mesothelioma, and malignant pleural effusion (cancer-related fluid around the lungs). It reported no new patient data but described earlier studies of intrapleural chemotherapy, immunotherapy and gene therapy. In one reviewed interferon-gamma trial in 22 patients with stage I-II mesothelioma, 18.1% had a complete and 4.5% a partial response, all in stage I patients. In the initial 12-patient cohort of a phase I measles-virus trial, median overall survival was 449 days (95% confidence interval 221 to 484), with follow-up ongoing. The authors noted that one reviewed study was nonrandomized, another was a single case report, and no survival benefit had been attributed to intrapleural immunotherapy. The review did not study asbestos exposure. Asbestos came up twice: the authors cited work suggesting exposure worsens immune dysfunction in mesothelioma, and noted that reviewed mouse studies used cell lines created by injecting crocidolite asbestos. The authors concluded that the pleural space is a unique target for such therapies and that combined approaches may prove necessary.

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: Narrative review of published and ongoing studies of intrapleural (intracavitary) therapies; no new data collected by the authors
• Who was studied: The reviewed studies involved patients with pleural malignancies, chiefly malignant mesothelioma, and patients with malignant pleural effusion (including effusion from non-small cell lung cancer). Some cell-line and animal studies were also reviewed.
• Exposure: Not an asbestos exposure study. The 'exposures' reviewed were treatments given into the pleural space: chemotherapy (cisplatin and others, sometimes heated), cytokine and innate immunotherapies, gene therapies and CAR T cells. Asbestos came up in two ways. First, as background on immune dysfunction in mesothelioma. Second, as a laboratory tool: crocidolite asbestos was injected to create the cell lines behind the mouse mesothelioma models used in reviewed preclinical studies.
• Main results:
  • Reviewed study (Boutin and colleagues): in 22 patients with stage I-II mesothelioma given intrapleural interferon-gamma, there was a complete response in 18.1% and a partial response in 4.5%, all in stage I patients
  • Reviewed multicenter phase II trial of intrapleural interferon-gamma: of 89 patients, 9% had a complete response and 10.1% a partial response. The 'ORR' (described in the article as overall risk reduction) was 20% overall and 45% in the stage I subset.
  • Reviewed study (Goey and colleagues) of daily intrapleural interleukin-2: partial response rate of 19%, median time to progression 12 months
  • Reviewed phase II trial (Yoshida and colleagues) in 105 patients with malignant pleural effusion from non-small cell lung cancer: pleural progression-free survival at 4 weeks was 75.8% with OK-432, 68.6% with bleomycin and 70.6% with no intrapleural therapy
  • Reviewed phase I measles-virus (MV-NIS) study in 12 patients with malignant pleural mesothelioma: no dose-limiting adverse events and disease stability in 67%. In the initial cohort, median overall survival was 449 days (95% confidence interval 221 to 484), with long-term follow-up ongoing.
  • Reviewed adenovirus HSVtk gene therapy trials in mesothelioma: two patients at higher doses remained alive for 8 and 14 years, respectively
  • Reviewed heated intrapleural chemotherapy experience: some patients developed inflammatory and fibrotic lung injury when the technique was used with lung-sparing surgery
  • Background statement citing other studies: immune dysfunction seems to be exacerbated in mesothelioma as a consequence of asbestos exposure
• The authors' conclusion: The authors concluded that the pleural space offers a unique target for intracavitary therapies that may decrease the morbidity and mortality of malignant pleural disease, with less systemic toxicity. They added that combination approaches may prove necessary for major improvements in outcome.
• Limitations the authors state:
  • The authors noted that no survival benefit has been attributed to intrapleural immunotherapy
  • The authors cautioned that one reviewed chemotherapy study (Baba and colleagues) was nonrandomized
  • The authors cautioned that the intrapleural cisplatin result in plasma cell leukemia came from a single case report, with other possible explanations
  • The authors stated that translating gene-therapy immune responses into meaningful clinical benefit remains a challenge

Topics

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

Medical terms in this study, explained in our Lexicon: Biopsy.

Related studies

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• The CUL4A ubiquitin ligase is a potential therapeutic target in skin cancer and other malignancies — J. Hannah, P.B. Zhou (2013)
• Surgery followed by intracavitary plus systemic chemotherapy in malignant pleural mesothelioma — M. Colleoni, F. Sartori, et al. (1996)
• Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma — D.L. Pouliquen, B. Nawrocki-Raby, et al. (2017)
• Progress report on the palliative therapy of 100 patients with neoplastic effusions by intracavitary low-dose interleukin-2 — P. Lissoni, M. Mandalà, et al. (2001)
• Local treatment of malignant pleural mesothelioma with intracavitary cytosine-arabinoside and cisplatin — E. Aitini, E. Pasquini, et al. (1992)

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