Phase I clinical trial testing the dose escalation and expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin administration (PITHAC) for the management of pleural carcinosis.
Louis-Emmanuel Chriqui, Etienne Abdelnour-Berchtold, Edoardo Zanfrini, Severine Devesa-Perez, Michel Gonzalez, Thorsten Krueger, Kim Ellefsen, Alice Destaillats, David Bonnet, Martin Hübner, Hasna Bouchaab, Michal Bassani-Sternberg, Solange Peters, Sabrina Cavin, Jean Y Perentes
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Abstract
Background: Pleural carcinosis originates from various cancers. Its management consists in systemic therapies combined to dyspnea relief procedures. Prior studies have tested hyperthermic intrathoracic chemotherapy to treat pleural carcinosis with interesting patient survival results. However, these approaches were limited by local toxicity. Pre-clinical data have shown that hyperthermia combined to local pleural chemotherapy increased the immune response against tumors. Recently, pressurized intraperitoneal aerosol chemotherapies (PIPAC) showed improved cytostatic penetration in abdominal carcinosis with a 10-fold-lower chemotherapy dose and minimal side-effects. This approach was also tested in limited numbers of patients with pleural carcinosis but never combined with hyperthermia.
Methods: Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin (PITHAC) is an open-label dose-escalation phase I trial. Patients with pleural carcinosis, eligible for the surgical management of their pleural effusion can be enrolled. Cisplatin (7.5-12-5-35-70 mg/m2) heated at 39±1 °C is delivered into the thoracic cavity before the surgical effusion management. Initially, the study consists in a dose escalation of the four different cisplatin doses. The primary endpoint is the maximal tolerated dose of cisplatin administered by PITHAC. The secondary and translational endpoints are adverse events and the immune response directed against cancer following PITHAC. There is then an expansion phase at the recommended cisplatin dose on an additional 15 patients with identical outcomes.
Discussion: Pressurized intrathoracic delivery of chemotherapy under hyperthermic conditions was never tested so far. We plan to determine the safety of such an approach in patients managed for pleural carcinosis. If proven safe, PITHAC could be combined with systemic immunotherapies for the management of cancer.
期刊介绍：
Cancer Treatment and Research Communications is an international peer-reviewed publication dedicated to providing comprehensive basic, translational, and clinical oncology research. The journal is devoted to articles on detection, diagnosis, prevention, policy, and treatment of cancer and provides a global forum for the nurturing and development of future generations of oncology scientists. Cancer Treatment and Research Communications publishes comprehensive reviews and original studies describing various aspects of basic through clinical research of all tumor types. The journal also accepts clinical studies in oncology, with an emphasis on prospective early phase clinical trials. Specific areas of interest include basic, translational, and clinical research and mechanistic approaches; cancer biology; molecular carcinogenesis; genetics and genomics; stem cell and developmental biology; immunology; molecular and cellular oncology; systems biology; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; cancer policy; and integration of various approaches. Our mission is to be the premier source of relevant information through promoting excellence in research and facilitating the timely translation of that science to health care and clinical practice.
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