Elsevier

Clinics in Chest Medicine

Volume 34, Issue 3, September 2013, Pages 501-513
Clinics in Chest Medicine

Intracavitary Therapeutics for Pleural Malignancies

https://doi.org/10.1016/j.ccm.2013.04.007Get rights and content

Section snippets

Key points

  • Pleural malignancies are ideal for novel therapeutic approaches, because they are invariable fatal with few treatment options.

  • Intrapleural chemotherapy has only marginal benefit in pleural malignancies, but may prove efficacious with hyperthermic chemotherapy administered in combination with maximal tumor debulking.

  • Intrapleural immunotherapies may be most effective in those patients with early-stage pleural malignancy, such as mesotheliomas limited to the parietal pleura, and may prove superior

IP chemotherapy

Pleural malignancies such as mesothelioma are characterized by predominantly locoregional spread of disease for which surgical resection can be attempted, but with the certainty of residual microscopic disease. Therefore, there is a rationale for attempted local control of pleural malignancies by IP instillation of cytotoxic chemotherapeutic agents. For example, Refaely and colleagues11 in 2002 reported their experience with intraoperative IP hyperthermic cisplatin chemotherapy in 15 patients

IP immunotherapy

Among the malignancies of the pleural space, MM has been thought to be resistant to immunotherapy compared with more classically immunogenic tumors such as melanoma or renal cell carcinoma. In these diseases, exogenous cytokines, monoclonal antibodies, and tumor vaccines have contributed to antitumor responses. Immunotherapy has been attempted in MM, despite observations of a significant immunosuppressive tumor microenvironment.20, 21, 22 In addition to the tumor’s innate mechanisms of immune

IP gene therapy

Advances in molecular genetics and gene transfer technology facilitated the development of gene therapy: the modification of the genetic makeup of cells for therapeutic purposes. The concept of gene therapy now encompasses the treatment of any pathophysiologic state based on the transfer of genetic material, including complementary DNA (cDNA), full-length genes, small-interfering RNA (si-RNA), or oligonucleotides. This definition also includes approaches involving delivery of genetically

Vectors used in pleural gene therapy

The first requirement for successful gene therapy is efficient gene delivery and a variety of viral and nonviral gene transfer vectors have been developed.36, 37 As summarized in Table 1, each of these vectors has certain advantages with regard to DNA carrying capacity, types of cells targeted, in vivo gene transfer efficiency, duration of expression, and induction of inflammation.

IP delivery of tumor suppressor genes

One of the primary approaches to cancer gene therapy has been mutation compensation: the replacement of absent or mutated tumor suppressor genes responsible, in part, for the malignant phenotype of the cancer cell. Intratumoral delivery of the wild-type p53 (wt-p53) gene, for example, has been used in human gene therapy trials for lung cancer and other solid tumors. Despite most mesotheliomas having wt-p53, p53 function may be abnormal in mesothelioma cells secondary to p53 binding by inhibitor

Summary

Pleural malignancies are ideal for novel therapeutic approaches, because they are invariably fatal, with few treatment options. In addition, research efforts into the efficacy of novel therapies are aided by the ease of access of the pleural space for thoracoscopic examination and/or pleural fluid sampling. IP chemotherapy has only marginal benefit in pleural malignancies, but may prove efficacious with hyperthermic chemotherapy administered in combination with maximal tumor debulking. IP

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