{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:34:18Z","timestamp":1790696058922,"version":"4.1.0"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"30","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,10,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To determine the maximum-tolerated dose (MTD), efficacy, safety, and pharmacokinetics of oblimersen sodium in patients with advanced chronic lymphocytic leukemia (CLL). <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Eligible patients had relapsed or refractory CLL after treatment with fludarabine. Oblimersen was administered at doses ranging from 3 to 7 mg\/kg\/d as a 5-day continuous intravenous infusion in cycle 1 and as a 7-day continuous intravenous infusion in subsequent cycles every 3 weeks in stable or responding patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Forty patients were enrolled and treated (14 patients in phase I and 26 patients in phase II). Dose-limiting reactions in phase I included hypotension and fever, and the MTD for phase II dosing was established at 3 mg\/kg\/d. Two (8%) of 26 assessable patients achieved a partial response. Other evidence of antitumor activity included \u2265 50% reduction in splenomegaly (seven of 17 patients; 41%), complete disappearance of hepatomegaly (two of seven patients; 29%), \u2265 50% reduction of lymphadenopathy (seven of 22 patients; 32%), and \u2265 50% reduction in circulating lymphocyte counts (11 of 22 patients; 50%). Adverse events included transient hypotension, fever, fatigue, night sweats, diarrhea, nausea, vomiting, hypokalemia, and cough. Plasma concentrations of oblimersen (parent drug) and its major metabolites were variable. Renal clearance represented only a small portion of total parent drug clearance. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Dosing with oblimersen sodium in patients with CLL is limited by development of a cytokine release syndrome that is characterized by fever, hypotension, and back pain. Oblimersen sodium has modest single-agent activity in heavily pretreated patients with advanced CLL, and further evaluation of its activity in combination with cytotoxic drugs is warranted. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.02.4364","type":"journal-article","created":{"date-parts":[[2005,9,27]],"date-time":"2005-09-27T00:44:00Z","timestamp":1127781840000},"page":"7697-7702","source":"Crossref","is-referenced-by-count":169,"title":["Phase I to II Multicenter Study of Oblimersen Sodium, a Bcl-2 Antisense Oligonucleotide, in Patients With Advanced Chronic Lymphocytic Leukemia"],"prefix":"10.1200","volume":"23","author":[{"given":"Susan M.","family":"O'Brien","sequence":"first","affiliation":[{"name":"From the M.D. Anderson Cancer Center, Houston; US Oncology, Dallas, TX; Genta Incorporated, Berkeley Heights, NJ; Long Island Jewish Medical Center, New Hyde Park, NY; Moscow Regional Clinical Research Institute; and Russian Academy of Medical Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles C.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"From the M.D. Anderson Cancer Center, Houston; US Oncology, Dallas, TX; Genta Incorporated, Berkeley Heights, NJ; Long Island Jewish Medical Center, New Hyde Park, NY; Moscow Regional Clinical Research Institute; and Russian Academy of Medical Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoliy K.","family":"Golenkov","sequence":"additional","affiliation":[{"name":"From the M.D. Anderson Cancer Center, Houston; US Oncology, Dallas, TX; Genta Incorporated, Berkeley Heights, NJ; Long Island Jewish Medical Center, New Hyde Park, NY; Moscow Regional Clinical Research Institute; and Russian Academy of Medical Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna G.","family":"Turkina","sequence":"additional","affiliation":[{"name":"From the M.D. Anderson Cancer Center, Houston; US Oncology, Dallas, TX; Genta Incorporated, Berkeley Heights, NJ; Long Island Jewish Medical Center, New Hyde Park, NY; Moscow Regional Clinical Research Institute; and Russian Academy of Medical Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Novick","sequence":"additional","affiliation":[{"name":"From the M.D. Anderson Cancer Center, Houston; US Oncology, Dallas, TX; Genta Incorporated, Berkeley Heights, NJ; Long Island Jewish Medical Center, New Hyde Park, NY; Moscow Regional Clinical Research Institute; and Russian Academy of Medical Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanti R.","family":"Rai","sequence":"additional","affiliation":[{"name":"From the M.D. Anderson Cancer Center, Houston; US Oncology, Dallas, TX; Genta Incorporated, Berkeley Heights, NJ; Long Island Jewish Medical Center, New Hyde Park, NY; Moscow Regional Clinical Research Institute; and Russian Academy of Medical Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Wu GS, El-Deiry WS: Apoptotic death of tumor cells correlates with chemosensitivity, independent of p53 or Bcl-2. 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