1. A phase I trial of bortezomib in combination with everolimus for treatment of relapsed/refractory non-Hodgkin lymphoma.
- Author
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Hill BT, Smith MR, Shelley M, Jagadeesh D, Dean RM, Pohlman B, Sweetenham JW, Bolwell BJ, and Smith SD
- Subjects
- Adult, Aged, Aged, 80 and over, Bortezomib administration & dosage, Everolimus administration & dosage, Female, Follow-Up Studies, Humans, Lymphoma, Non-Hodgkin pathology, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Recurrence, Local pathology, Prognosis, Prospective Studies, Remission Induction, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Drug Resistance, Neoplasm drug effects, Lymphoma, Non-Hodgkin drug therapy, Neoplasm Recurrence, Local drug therapy, Salvage Therapy
- Abstract
B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling cell proliferation and apoptosis. Combined proteasome and mTOR inhibition, demonstrated with bortezomib and everolimus in a preclinical model, thus warrants evaluation in humans. We conducted a phase I study to identify the maximum tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r) NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as 5 mg everolimus daily with 1.3 mg/m
2 bortezomib d1, 4, 8, and 11 every 21 days. Of 25 response-evaluable patients there was one complete response in a patient with MCL and three partial responses (two MCL, one FL) for an overall response rate of 16%. In conclusion, the combination of everolimus and bortezomib results in dose limiting thrombocytopenia, but is tolerable. This combination has limited clinical activity in heavily pretreated NHL.- Published
- 2018
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