Interleukin-2 based systemic and locoregional immunology

The major impact of recent clinical research with interleukin-2 (IL2) has been the demonstration that a strictly immunological manipulation can mediate the regression of established cancer in humans through the activation of cytotoxic lymphocytes and the release of secondary cytokines. Since 1985 a variety of clinical studies have been carried out in metastatic cancer patients with the use of interleukins, interferons, and Iymphokine activated killer cells. These studies have either employed a single agent approach or combined modality treatment also including hormonal and chemotherapy. Although the majority of human cancers are systemic diseases by nature, some tumor types are predilected to reside in one organ site or cavity. For example, metastatic colon cancer is often confined to the liver for prolonged periods of time. Ovarian cancer is usually restricted to the abdominal cavity, whereas mesothelioma mostly does not extend the pleural cavity until death. It is for these reasons that the clinical investigations described in this thesis are based on a systemic approach on the one hand and on a locoregional approach on the other hand in selected tumor types. The study treatments comprised single agent IL2 and combinations of IL2 and interferon (IFN)-a with or without chemotherapy. Regarding the systemic administration of IL2 based immunotherapy, we have chosen for a constant infusion schedule rather than intermittent bolus intravenous administration, based on available data in the literature of treatment equivalence and less toxicity accompanied with the continuous infusion method. For the locoregional treatment of liver metastases we have used a continuous arterial infusion method.

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