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Ann Thorac Surg 2004;78:1772-1773
© 2004 The Society of Thoracic Surgeons
Department of Surgery, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA
rvertree{at}utmb.edu
jzwische{at}utmb.edu
Hyperthermia has a long history in the treatment of various forms of cancer dating back to Coley's work first published in 1893. The literature is replete with examples that demonstrate that hyperthermia is selectively lethal to various subsets of cancers. Currently, a major area of interest in cancer research is the selective induction of apoptosis in targeted neoplastic cells, not damaging normal cells. Although, many studies have shown that hyperthermia in the correct dosage may induce apoptosis, neither the mechanisms nor targets are clearly defined.
Cis-platinum, an alkylating antineoplastic agent enters the cell through diffusion and has been shown to cause apoptosis through DNA binding. Systemic treatment with cis-platinum is often limited by adverse side effects that manifest at higher doses. In theory, the combination of hyperthermia and cis-platinum may act synergistically for two important reasons: the increased temperature facilitates entry of cis-platinum into the cancer cell, and the increased temperature results in an increased metabolic rate magnifying the effect of cis-platinum.
The current article is the second in a series by this group (Matsuzaki and coworkers) on intrapleural hyperthermic perfusion with chemotherapy (IPHC). They have selected regional perfusion as the method of delivery to direct a lethal dose directly to the target tumor, sparing adjacent tissues. This occurs because the chosen method of perfusion is an extravascular intrathoracic continuous pleural wash that delivers constant exposure to both cis-platinum and hyperthermia. Therefore, drug and thermal dose can be delivered directly to the tumor present in the pleura. Their first article discussed this technique in detail whereas this article examines the outcomes of IPHC in 11 patients with Stage IIIB malignant pleuritis. In the current article, they use a commercially available and established method to detect change in genomic DNA that is a hallmark of apoptosis and present a semiquantitative means of measuring the effect of therapy. Importantly, not only does this method quantitate the effectiveness of the intervention, but it may prove predictive of outcomes. The investigators have correctly stated that the lack of randomized studies prohibits them from determining whether the IPHC group lived longer, or that the increased apoptosis could be translated into clinical significance.
We applaud this group's efforts in their development of IPHC and are encouraged by this cohort of patients with respect to the increase in apoptotic cells after IPHC. The apoptosis assay technique has an immediate clinical application that may present us with a ‘yardstick’ by which to measure the effectiveness of a treatment. Their results confirm the feasibility of the IPHC technique, which achieves regional-hyperthermia induction of apoptosis. Much study remains, the IPHC hyperthermia technique, patient selection criteria, disease response and multi-modal adjunctive agent effect need to be established first. Then prospective randomized, controlled, multicenter trials can be conducted to determine the risk or benefit of IPHC for malignant pleuritis.
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