دورية أكاديمية
Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (bolus) infusion schedule of alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms.
| العنوان: | Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (bolus) infusion schedule of alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms. |
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| المؤلفون: | Holkova B; Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia. bholkova@mcvh-vcu.edu., Kmieciak M; Massey Cancer Center and., Perkins EB; Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia., Bose P; Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia., Baz RC; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida., Roodman GD; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania., Stuart RK; Department of Medicine, Medical University of South Carolina, Charleston, South Carolina., Ramakrishnan V; Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia., Wan W; Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia., Peer CJ; Center for Cancer Research, NCI, NIH, Bethesda, Maryland., Dawson J; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida., Kang L; James A. Haley Veterans' Hospital, Tampa, Florida., Honeycutt C; Massey Cancer Center and., Tombes MB; Massey Cancer Center and., Shrader E; Massey Cancer Center and., Weir-Wiggins C; Massey Cancer Center and., Wellons M; Massey Cancer Center and., Sankala H; Massey Cancer Center and., Hogan KT; Massey Cancer Center and., Colevas AD; Cancer Therapy Evaluation Program, NCI, NIH, Bethesda, Maryland. Departments of., Doyle LA; Cancer Therapy Evaluation Program, NCI, NIH, Bethesda, Maryland. Departments of., Figg WD; Center for Cancer Research, NCI, NIH, Bethesda, Maryland., Coppola D; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida., Roberts JD; Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia., Sullivan D; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida., Grant S; Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2014 Nov 15; Vol. 20 (22), pp. 5652-62. Date of Electronic Publication: 2014 Sep 23. |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , B-Lymphocytes/*pathology , Lymphoproliferative Disorders/*drug therapy , Lymphoproliferative Disorders/*pathology, Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Boronic Acids/administration & dosage ; Boronic Acids/pharmacokinetics ; Bortezomib ; Combined Modality Therapy ; Drug Administration Schedule ; Drug Monitoring ; Female ; Flavonoids/administration & dosage ; Flavonoids/pharmacokinetics ; Humans ; Lymphoproliferative Disorders/diagnosis ; Male ; Middle Aged ; Piperidines/administration & dosage ; Piperidines/pharmacokinetics ; Pyrazines/administration & dosage ; Pyrazines/pharmacokinetics ; Recurrence ; Retreatment ; Treatment Outcome |
| مستخلص: | Purpose: This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma). Experimental Design: Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted. Results: A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m(2) for bortezomib and 40 mg/m(2) for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common nonhematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses. Conclusions: The combination of bortezomib and alvocidib is tolerable, and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory multiple myeloma or indolent non-Hodgkin lymphoma. As the nonhybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies. (©2014 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | KL2 TR000057 United States TR NCATS NIH HHS; R01 CA93738 United States CA NCI NIH HHS; N01 HHSN261201100100C United States PHS HHS; R01 CA100866 United States CA NCI NIH HHS; UL1 TR000058 United States TR NCATS NIH HHS; R01 CA167708 United States CA NCI NIH HHS; M01 RR000065 United States RR NCRR NIH HHS; KL2TR000057 United States TR NCATS NIH HHS; R01 CA093738 United States CA NCI NIH HHS; P30 CA076292 United States CA NCI NIH HHS; R21 CA110953 United States CA NCI NIH HHS; P50 CA130805 United States CA NCI NIH HHS; UL1 TR000142 United States TR NCATS NIH HHS; P30 CA016059 United States CA NCI NIH HHS; P30 CA76292 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Boronic Acids) 0 (Flavonoids) 0 (Piperidines) 0 (Pyrazines) 45AD6X575G (alvocidib) 69G8BD63PP (Bortezomib) |
| تواريخ الأحداث: | Date Created: 20140925 Date Completed: 20150709 Latest Revision: 20240620 |
| رمز التحديث: | 20240620 |
| مُعرف محوري في PubMed: | PMC4233160 |
| DOI: | 10.1158/1078-0432.CCR-14-0805 |
| PMID: | 25248382 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-14-0805 |