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Semin Respir Crit Care Med 2023; 44(04): 462-467
DOI: 10.1055/s-0043-1769094
Review Article

Intrapleural Anticancer Therapy for Malignant Pleural Diseases: Facts or Fiction?

Abhinav Agrawal   *
1   Division of Pulmonary, Critical Care and Sleep Medicine, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York
,
Udit Chaddha   *
2   Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
,
Samira Shojaee
3   Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
,
Fabien Maldonado
3   Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
› Author Affiliations Funding None.
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Abstract

Malignant pleural diseases involves both primary pleural malignancies (e.g., mesothelioma) as well as metastatic disease involving the pleura. The management of primary pleural malignancies remains a challenge, given their limited response to conventional treatments such as surgery, systemic chemotherapy, and immunotherapy. In this article, we aimed to review the management of primary pleural malignancy as well as malignant pleural effusion and assess the current state of intrapleural anticancer therapies. We review the role intrapleural chemotherapy, immunotherapy, and immunogene therapy, as well as oncolytic viral, therapy and intrapleural drug device combination. We further discuss that while the pleural space offers a unique opportunity for local therapy as an adjuvant option to systemic therapy and may help decrease some of the systemic side effects, further patient outcome-oriented research is needed to determine the exact role of these treatments within the armamentarium of currently available options.

Keywords

intrapleural chemotherapy - intrapleural immunotherapy - malignant pleural diseases - mesothelioma - malignant pleural effusion - immunogene therapy

* First coauthors.




Publication History

Article published online:
12 June 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Clive AO, Kahan BC, Hooper CE. et al. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score. Thorax 2014; 69 (12) 1098-1104
    CrossrefPubMedGoogle Scholar
  • 2 Vogelzang NJ, Rusthoven JJ, Symanowski J. et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21 (14) 2636-2644
    CrossrefPubMedGoogle Scholar
  • 3 Zalcman G, Mazieres J, Margery J. et al; French Cooperative Thoracic Intergroup (IFCT). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet 2016; 387 (10026): 1405-1414
    CrossrefPubMedGoogle Scholar
  • 4 Baas P, Scherpereel A, Nowak AK. et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet 2021; 397 (10272): 375-386
    CrossrefPubMedGoogle Scholar
  • 5 Sugarbaker DJ, Flores RM, Jaklitsch MT. et al. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 1999; 117 (01) 54-63 , discussion 63–65
    CrossrefPubMedGoogle Scholar
  • 6 Molina S, Martinez-Zayas G, Sainz PV. et al. Breast and lung effusion survival score models: improving survival prediction in patients with malignant pleural effusion and metastasis. Chest 2021; 160 (03) 1075-1094
    CrossrefPubMedGoogle Scholar
  • 7 Feller-Kopman DJ, Reddy CB, DeCamp MM. et al. Management of malignant pleural effusions. an official ATS/STS/STR clinical practice guideline. Am J Respir Crit Care Med 2018; 198 (07) 839-849
    CrossrefPubMedGoogle Scholar
  • 8 Ost DE, Niu J, Zhao H, Grosu HB, Giordano SH. Quality gaps and comparative effectiveness of management strategies for recurrent malignant pleural effusions. Chest 2018; 153 (02) 438-452
    CrossrefPubMedGoogle Scholar
  • 9 Asciak R, Hallifax RJ, Mercer RM. et al. The hospital and patient burden of indwelling pleural catheters: a retrospective case series of 210 indwelling pleural catheter insertions. Respiration 2019; 97 (01) 70-77
    CrossrefPubMedGoogle Scholar
  • 10 Hu R, Jiang H, Li H, Wei D, Wang G, Ma S. Intrapleural perfusion thermo-chemotherapy for pleural effusion caused by lung carcinoma under VATS. J Thorac Dis 2017; 9 (05) 1317-1321
    CrossrefPubMedGoogle Scholar
  • 11 Song K, Flores RM. A narrative review of hyperthermic intrathoracic chemotherapy for advanced lung cancer. Ann Transl Med 2021; 9 (11) 958
    CrossrefPubMedGoogle Scholar
  • 12 Biaoxue R, Xiguang C, Hua L, Wenlong G, Shuanying Y. Thoracic perfusion of recombinant human endostatin (Endostar) combined with chemotherapeutic agents versus chemotherapeutic agents alone for treating malignant pleural effusions: a systematic evaluation and meta-analysis. BMC Cancer 2016; 16 (01) 888
    CrossrefPubMedGoogle Scholar
  • 13 Goéré D, Passot G, Gelli M. et al. Complete cytoreductive surgery plus HIPEC for peritoneal metastases from unusual cancer sites of origin: results from a worldwide analysis issue of the Peritoneal Surface Oncology Group International (PSOGI). Int J Hyperthermia 2017; 33 (05) 520-527
    CrossrefPubMedGoogle Scholar
  • 14 Ambrogi MC, Bertoglio P, Aprile V. et al. Diaphragm and lung-preserving surgery with hyperthermic chemotherapy for malignant pleural mesothelioma: a 10-year experience. J Thorac Cardiovasc Surg 2018; 155 (04) 1857-1866.e2
    CrossrefPubMedGoogle Scholar
  • 15 Baldini EH, Richards WG, Gill RR. et al. Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2015; 149 (05) 1374-1381
    CrossrefPubMedGoogle Scholar
  • 16 Markowiak T, Larisch C, Hofmann HS, Ried M. Hyperthermic intrathoracic chemotherapy (HITHOC): narrative review of the current literature, recommendations and future studies. Ann Transl Med 2021; 9 (11) 955
    CrossrefPubMedGoogle Scholar
  • 17 Migliore M, Ried M, Molins L. et al. Hyperthermic intrathoracic chemotherapy (HITHOC) should be included in the guidelines for malignant pleural mesothelioma. Ann Transl Med 2021; 9 (11) 960
    CrossrefPubMedGoogle Scholar
  • 18 Shigemura N, Akashi A, Ohta M, Matsuda H. Combined surgery of intrapleural perfusion hyperthermic chemotherapy and panpleuropneumonectomy for lung cancer with advanced pleural spread: a pilot study. Interact Cardiovasc Thorac Surg 2003; 2 (04) 671-675
    CrossrefPubMedGoogle Scholar
  • 19 Kimura M, Tojo T, Naito H, Nagata Y, Kawai N, Taniguchi S. Effects of a simple intraoperative intrathoracic hyperthermotherapy for lung cancer with malignant pleural effusion or dissemination. Interact Cardiovasc Thorac Surg 2010; 10 (04) 568-571
    CrossrefPubMedGoogle Scholar
  • 20 Migliore M, Nardini M. Does cytoreduction surgery and hyperthermic intrathoracic chemotherapy prolong survival in patients with N0-N1 nonsmall cell lung cancer and malignant pleural effusion?. Eur Respir Rev 2019; 28 (153) 190018
    CrossrefPubMedGoogle Scholar
  • 21 Kleontas A, Sioga A, Pandria N. et al. Clinical factors affecting the survival of patients diagnosed with non-small cell lung cancer and metastatic malignant pleural effusion, treated with hyperthermic intrathoracic chemotherapy or chemical talc pleurodesis: a monocentric, prospective, randomized trial. J Thorac Dis 2019; 11 (05) 1788-1798
    CrossrefPubMedGoogle Scholar
  • 22 Sack U, Hoffmann M, Zhao XJ. et al. Vascular endothelial growth factor in pleural effusions of different origin. Eur Respir J 2005; 25 (04) 600-604
    CrossrefPubMedGoogle Scholar
  • 23 Mohammed KA, Nasreen N, Hardwick J, Logie CS, Patterson CE, Antony VB. Bacterial induction of pleural mesothelial monolayer barrier dysfunction. Am J Physiol Lung Cell Mol Physiol 2001; 281 (01) L119-L125
    CrossrefPubMedGoogle Scholar
  • 24 Hu Y, Zhou Z, Luo M. Efficacy and safety of endostar combined with cisplatin in treatment of non-small cell lung cancer with malignant pleural effusion: a meta-analysis. Medicine (Baltimore) 2022; 101 (52) e32207
    CrossrefPubMedGoogle Scholar
  • 25 Wang CQ, Liu FY, Wang W. Thoracic perfusion of lobaplatin combined with endostar for treating malignant pleural effusions: a meta-analysis and systematic review. Medicine (Baltimore) 2022; 101 (40) e30749
    CrossrefPubMedGoogle Scholar
  • 26 Sandler A. Bevacizumab in non small cell lung cancer. Clin Cancer Res 2007; 13 (15 Pt 2): s4613-s4616
    CrossrefPubMedGoogle Scholar
  • 27 Du N, Li X, Li F. et al. Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer-mediated malignant pleural effusion. Oncol Rep 2013; 29 (06) 2332-2340
    CrossrefPubMedGoogle Scholar
  • 28 Qi N, Li F, Li X, Kang H, Zhao H, Du N. Combination use of paclitaxel and Avastin enhances treatment effect for the NSCLC patients with malignant pleural effusion. Medicine (Baltimore) 2016; 95 (47) e5392
    CrossrefPubMedGoogle Scholar
  • 29 Di W, Yue C, Ziran Z. et al. A phase II study of bevacizumab in non-squamous, non-small-cell lung cancer patients with malignant pleural effusion. Future Oncol 2022; 18 (06) 669-677
    CrossrefPubMedGoogle Scholar
  • 30 Karampinis I, Dionysopoulou A, Galata C. et al. Hyperthermic intrathoracic chemotherapy for the treatment of malignant pleural effusion caused by breast and ovarian cancer: a systematic literature review and pooled analysis. Thorac Cancer 2022; 13 (07) 883-888
    CrossrefPubMedGoogle Scholar
  • 31 Zhao Y, Yu L, Wang L. et al. Current status of and progress in the treatment of malignant pleural effusion of lung cancer. Front Oncol 2023; 12: 961440
    CrossrefPubMedGoogle Scholar
  • 32 Li X, Wu G, Chen C. et al. Intrapleural injection of anti-PD1 antibody: a novel management of malignant pleural effusion. Front Immunol 2021; 12: 760683
    CrossrefPubMedGoogle Scholar
  • 33 Hu CY, Zhang YH, Wang T. et al. Interleukin-2 reverses CD8(+) T cell exhaustion in clinical malignant pleural effusion of lung cancer. Clin Exp Immunol 2016; 186 (01) 106-114
    CrossrefPubMedGoogle Scholar
  • 34 Goey SH, Eggermont AM, Punt CJ. et al. Intrapleural administration of interleukin 2 in pleural mesothelioma: a phase I-II study. Br J Cancer 1995; 72 (05) 1283-1288
    CrossrefPubMedGoogle Scholar
  • 35 Boutin C, Viallat JR, Van Zandwijk N. et al. Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma. Cancer 1991; 67 (08) 2033-2037
    CrossrefPubMedGoogle Scholar
  • 36 Boutin C, Nussbaum E, Monnet I. et al. Intrapleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma. Cancer 1994; 74 (09) 2460-2467
    CrossrefPubMedGoogle Scholar
  • 37 Monnet I, Breau JL, Moro D. et al. Intrapleural infusion of activated macrophages and gamma-interferon in malignant pleural mesothelioma: a phase II study. Chest 2002; 121 (06) 1921-1927
    CrossrefPubMedGoogle Scholar
  • 38 Beatty GL, Haas AR, Maus MV. et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res 2014; 2 (02) 112-120
    CrossrefPubMedGoogle Scholar
  • 39 Haas AR, Tanyi JL, O'Hara MH. et al. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers. Mol Ther 2019; 27 (11) 1919-1929
    CrossrefPubMedGoogle Scholar
  • 40 Adusumilli PS, Zauderer MG, Rivière I. et al. A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab. Cancer Discov 2021; 11 (11) 2748-2763
    CrossrefPubMedGoogle Scholar
  • 41 Uchida A, Micksche M. Lysis of fresh human tumor cells by autologous large granular lymphocytes from peripheral blood and pleural effusions. Int J Cancer 1983; 32 (01) 37-44
    CrossrefPubMedGoogle Scholar
  • 42 Uchida A, Micksche M, Hoshino T. Intrapleural administration of OK432 in cancer patients: augmentation of autologous tumor killing activity of tumor-associated large granular lymphocytes. Cancer Immunol Immunother 1984; 18 (01) 5-12
    CrossrefPubMedGoogle Scholar
  • 43 Ishida A, Miyazawa T, Miyazu Y. et al. Intrapleural cisplatin and OK432 therapy for malignant pleural effusion caused by non-small cell lung cancer. Respirology 2006; 11 (01) 90-97
    CrossrefPubMedGoogle Scholar
  • 44 Yoshida K, Sugiura T, Takifuji N. et al. 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. Lung Cancer 2007; 58 (03) 362-368
    CrossrefPubMedGoogle Scholar
  • 45 Sterman DH, Recio A, Carroll RG. et al. A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses. Clin Cancer Res 2007; 13 (15 Pt 1): 4456-4466
    CrossrefPubMedGoogle Scholar
  • 46 Sterman DH, Recio A, Haas AR. et al. A phase I trial of repeated intrapleural adenoviral-mediated interferon-beta gene transfer for mesothelioma and metastatic pleural effusions. Mol Ther 2010; 18 (04) 852-860
    CrossrefPubMedGoogle Scholar
  • 47 Sterman DH, Haas A, Moon E. et al. A trial of intrapleural adenoviral-mediated interferon-α2b gene transfer for malignant pleural mesothelioma. Am J Respir Crit Care Med 2011; 184 (12) 1395-1399
    CrossrefPubMedGoogle Scholar
  • 48 Sterman DH, Alley E, Stevenson JP. et al. Pilot and feasibility trial evaluating immuno-gene therapy of malignant mesothelioma using intrapleural delivery of adenovirus-IFNα combined with chemotherapy. Clin Cancer Res 2016; 22 (15) 3791-3800
    CrossrefPubMedGoogle Scholar
  • 49 Aguilar LK, Shirley LA, Chung VM. et al. Gene-mediated cytotoxic immunotherapy as adjuvant to surgery or chemoradiation for pancreatic adenocarcinoma. Cancer Immunol Immunother 2015; 64 (06) 727-736
    CrossrefPubMedGoogle Scholar
  • 50 Aggarwal C, Haas AR, Metzger S. et al. Phase I study of intrapleural gene-mediated cytotoxic immunotherapy in patients with malignant pleural effusion. Mol Ther 2018; 26 (05) 1198-1205
    CrossrefPubMedGoogle Scholar
  • 51 Andtbacka RH, Kaufman HL, Collichio F. et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 2015; 33 (25) 2780-2788
    CrossrefPubMedGoogle Scholar
  • 52 Danson SJ, Conner J, Edwards JG. et al. Oncolytic herpesvirus therapy for mesothelioma - A phase I/IIa trial of intrapleural administration of HSV1716. Lung Cancer 2020; 150: 145-151
    CrossrefPubMedGoogle Scholar
  • 53 Friedberg JS, Culligan MJ, Mick R. et al. Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma. Ann Thorac Surg 2012; 93 (05) 1658-1665 , discussion 1665–1667
    CrossrefPubMedGoogle Scholar
  • 54 Simone II CB, Cengel KA. Photodynamic therapy for lung cancer and malignant pleural mesothelioma. Semin Oncol 2014; 41 (06) 820-830
    CrossrefPubMedGoogle Scholar
  • 55 Pass HI, Temeck BK, Kranda K. et al. Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma. Ann Surg Oncol 1997; 4 (08) 628-633
    CrossrefPubMedGoogle Scholar
  • 56 Munck C, Mordon SR, Scherpereel A, Porte H, Dhalluin X, Betrouni N. Intrapleural photodynamic therapy for mesothelioma: what place and which future?. Ann Thorac Surg 2015; 99 (06) 2237-2245
    CrossrefPubMedGoogle Scholar