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Phase II study of single‐agent bortezomib for the treatment of patients with fludarabine‐refractory B‐cell chronic lymphocytic leukemia
Author(s) -
Faderl Stefan,
Rai Kanti,
Gribben John,
Byrd John C.,
Flinn Ian W.,
O'Brien Susan,
Sheng Shihong,
Esseltine DixieLee,
Keating Michael J.
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22097
Subject(s) - medicine , fludarabine , neutropenia , bortezomib , chronic lymphocytic leukemia , gastroenterology , peripheral neuropathy , adverse effect , anemia , bendamustine , leukemia , oncology , chemotherapy , multiple myeloma , cyclophosphamide , diabetes mellitus , endocrinology
Therapeutic options are limited and the prognosis is poor for patients with fludarabine‐refractory B‐cell chronic lymphocytic leukemia (CLL). Bortezomib induces apoptosis in vitro in CLL cells, both alone and in combination, including in cells resistant to fludarabine or other agents. The aim of the current randomized, open‐label, Phase II study was to investigate the clinical activity of bortezomib in patients with fludarabine‐refractory B‐cell CLL. Twenty‐two patients with histologically confirmed B‐cell CLL were treated with bortezomib at doses of 1.0 mg/m 2 , 1.3 mg/m 2 , or 1.5 mg/m 2 on Days 1, 4, 8, and 11 of a 21‐day treatment cycle for a maximum of 9 cycles. None of 19 patients evaluable for response achieved complete remission or partial response; however, signs of biologic activity based on disease site responses (e.g., reduction in lymphocytosis, splenomegaly, and lymphadenopathy) were observed. In the 1.5 mg/m 2 dose group, a higher proportion of patients had stable disease, and a lower proportion had progressive disease compared with the 2 lower‐dose groups. Eleven patients, all in the 2 higher dose groups, experienced Grade 3/4 adverse events (AEs) (according to National Cancer Institute Common Toxicity Criteria [version 2.0]); 2 patients experienced Grade 4 neutropenia. Grade 3 hematologic AEs included anemia, neutropenia, thrombocytopenia, and hemolytic anemia; Grade 3 nervous system AEs included aphasia; peripheral neuropathy, not otherwise specified; and peripheral sensory neuropathy. Although no objective responses were achieved in patients with fludarabine‐refractory B‐cell CLL, single‐agent bortezomib demonstrated biologic activity. In view of the evidence for its activity, further exploration of bortezomib in combination with other agents is warranted. Cancer 2006. © 2006 American Cancer Society.