Patients with malignant pleural mesothelioma have a poor prognosis. Until recently, attempts to improve survival of patients using surgical therapy alone have been disappointing. Trimodality treatment using maximal cytoreductive surgery followed by adjuvant chemotherapy and radiation has increased survival up to 46% at 5 years in selected patients.1 It is extremely difficult to achieve a microscopically complete resection with surgery alone.2 Although metastases can occur distantly, the recurrence pattern in malignant pleural mesothelioma is predominantly locoregional. In Sugarbaker's analysis of a large cohort of patients undergoing extrapleural pneumonectomy (EPP), microscopic tumor involvement at the surgical margin played a significant role in survival, which supports the need for improved locoregional control.1 The use of intracavitary chemotherapy has been studied in abdominal malignancies as a method of locoregional control.3 Sugarbaker and colleagues studied heated intracavitary chemotherapy for gastrointestinal malignancies.4,5 A series of studies at Brigham and Women's Hospital was conducted to treat malignant pleural mesothelioma using this innovative technique. This methodology was applied to both EPP and pleurectomy and decortication (P/D) in selected patients. Techniques for hyperthermic intraoperative chemotherapy (HIOC) are presented along with its complications and pitfalls.
With intracavitary administration, chemotherapy agent enters the tumor cells directly by diffusion, which minimizes the toxic systemic effects of IV administration. The depth of penetration of the chemotherapeutic agent is limited to several millimeters deep to the surface of the cavity.6 Thus cytoreduction of the tumor to microscopic levels is very important if one is to achieve maximal benefits for this modality of treatment. Complete contact with any surface that might sequester cancerous cells from the chemotherapeutic agent is extremely important. The optimal timing of intracavitary chemotherapy lavage is immediately after resection of the tumor. This ensures maximal exposure of residual cancerous cells to the chemotherapy before there is development of adhesions or fibrinous exudates and while the volume of residual tumor is small enough to be penetrated by the agent.
Cisplatin is the chemotherapeutic agent used in our lavage protocol. The drug binds covalently to various macromolecules, including DNA, the apparent target.7 The effects of cisplatin on mesothelioma have been studied in the past, and it can be combined with cytoprotective agents or other drugs.8,9 The concentration of the drug with regional administration is up to 50-fold higher than with IV administration.10 Ratto and colleagues showed that levels of cisplatin given into the pleura are higher with hyperthermic perfusion than with normothermic perfusion.11 Heat increases cell permeability, alters cellular metabolism, and improves membrane transport of drugs. This has been demonstrated in animal and human studies.12,13 A synergistic effect of hyperthermia and cisplatin has been demonstrated.14,15 Intracavitary cisplatin and its benefits in thoracic malignancies have been studied in the past for both EPP and P/D.11,16
Two cytoprotective agents are used during HIOC. Sodium thiosulfate is a neutralizing agent with ...