Phase II trial of karenitecin in patients with malignant melanoma: clinical and translational study.

Purpose: A phase II trial of the novel camptothecin karenitecin (BNP1350) was conducted to determine its efficacy and tolerability in patients with metastatic melanoma. Patients were biopsied to determine topoisomerase expression at baseline and response to therapy.

Patients And Methods: Eligible patients had metastatic melanoma with up to three prior chemotherapy and/or any number of immunotherapy regimens.

Human topoisomerase IIalpha nuclear export is mediated by two CRM-1-dependent nuclear export signals.

Resistance to chemotherapeutic drugs is a major obstacle in the treatment of leukemia and multiple myeloma. We have previously found that myeloma and leukemic cells in transition from low-density log phase conditions to high-density plateau phase conditions export substantial amounts of endogenous topoisomerase II alpha from the nucleus to the cytoplasm. In order for topoisomerase-targeted chemotherapy to function, the topoisomerase target must have access to the nuclear DNA.