{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:44:45Z","timestamp":1790203485755,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,7,10]],"date-time":"2006-07-10T00:00:00Z","timestamp":1152489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Therapeutic options are limited and the prognosis is poor for patients with fludarabine\u2010refractory B\u2010cell 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\u2010label, Phase II study was to investigate the clinical activity of bortezomib in patients with fludarabine\u2010refractory B\u2010cell CLL. Twenty\u2010two patients with histologically confirmed B\u2010cell CLL were treated with bortezomib at doses of 1.0 mg\/m<jats:sup>2<\/jats:sup>, 1.3 mg\/m<jats:sup>2<\/jats:sup>, or 1.5 mg\/m<jats:sup>2<\/jats:sup> on Days 1, 4, 8, and 11 of a 21\u2010day 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<jats:sup>2<\/jats:sup> dose group, a higher proportion of patients had stable disease, and a lower proportion had progressive disease compared with the 2 lower\u2010dose 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\u2010refractory B\u2010cell CLL, single\u2010agent 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. \u00a9 2006 American Cancer Society.<\/jats:p>","DOI":"10.1002\/cncr.22097","type":"journal-article","created":{"date-parts":[[2006,7,10]],"date-time":"2006-07-10T14:02:04Z","timestamp":1152540124000},"page":"916-924","source":"Crossref","is-referenced-by-count":74,"title":["Phase II study of single\u2010agent bortezomib for the treatment of patients with fludarabine\u2010refractory B\u2010cell chronic lymphocytic leukemia"],"prefix":"10.1002","volume":"107","author":[{"given":"Stefan","family":"Faderl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanti","family":"Rai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gribben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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