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Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity
Open accessAbstract
Background Proteins of the BCL-2 family regulate clonal selection and survival of lymphocytes, and are frequently overexpressed in lymphomas. Navitoclax is a targeted high-affinity small molecule that inhibits the anti-apoptotic activity of BCL-2 and BCL-XL. We aimed to assess the safety and antitumour activity of navitoclax in patients with lymphoid tumours, and establish the drug's pharmacokinetic and pharmacodynamic profiles.Methods In this phase 1 dose-escalation study, patients (aged ≥18 years) with relapsed or refractory lymphoid malignancies were enrolled and treated at seven sites in the USA between November, 2006, and November, 2009. A modified Fibonacci 3+3 design was used to assign patients to receive oral navitoclax once daily by one of two dosing schedules: intermittently for the first 14 days of a 21-day cycle (14/21) at doses of 10, 20, 40, 80, 110, 160, 225, 315, or 440 mg/day; or continuously for 21 days of a 21-day cycle (21/21) at doses of 200, 275, 325, or 425 mg/day. Study endpoints were safety, maximum tolerated dose, pharmacokinetic profile, pharmacodynamic effects on platelets and T cells, and antitumour activity. This trial is registered with ClinicalTrials.gov, number NCT00406809.Findings 55 patients were enrolled (median age 59 years, IQR 51-67), 38 to receive the 14/21 dosing schedule, and 17 to receive the 21/21 dosing schedule. Common toxic effects included grade 1 or 2 anaemia (41 patients), infection (39), diarrhoea (31), nausea (29), and fatigue (21); and grade 3 or 4 thrombocytopenia (29), lymphocytopenia (18), and neutropenia (18). On the intermittent 14/21 schedule, dose-limiting toxic effects were hospital admissions for bronchitis (one) and pleural effusion (one), grade 3 increase in aminotransferases (one), grade 4 thrombocytopenia (one), and grade 3 cardiac arrhythmia (one). To reduce platelet nadir associated with intermittent 14/21 dosing, we assessed a 150 mg/day lead-in dose followed by a continuous 21/21 dosing schedule. On the 21/21 dosing schedule, two patients did not complete the first cycle and were excluded from assessment of dose-limiting toxic effects; dose-limiting toxic effects were grade 4 thrombocytopenia (one), grade 3 increase in aminotransferases (one), and grade 3 gastrointestinal bleeding (one). Navitoclax showed a pharmacodynamic effect on circulating platelets and T cells. Clinical responses occurred across the range of doses and in several tumour types. Ten of 46 patients with assessable disease had a partial response, and these responders had median progression-free survival of 455 days (IQR 40-218).Interpretation Navitoclax has a novel mechanism of peripheral thrombocytopenia and T-cell lymphopenia, attributable to high-affinity inhibition of BCL-XL and BCL-2, respectively. On the basis of these findings, a 150 mg 7-day lead-in dose followed by a 325 mg dose administered on a continuous 21/21 dosing schedule was selected for phase 2 study.Funding Abbott Laboratories, Genentech, and National Cancer Institute, National Institutes of Health.
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“Drugs with single or limited targets, such as Nutlin3a (an MDM2 inhibitor) or navitoclax (a BCL-2 inhibitor), can have off-target apoptotic effects on multiple non-Snc types, such as neutrophils and platelets in the case of navitoclax (75), making them panolytic.”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [75]
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“N can cause thrombocytopenia and neutropenia, even after brief exposures57,88–91”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [89]
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“these agents exhibited notable drawbacks, such as dose-dependent thrombocytopenia, variable therapeutic efficacy, and the emergence of resistance mechanisms.”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [33]
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“Trials assessing navitoclax as an anticancer agent report neutropenia and thrombocytopenia (Wilson et al. 2010).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Wilson et al. 2010
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“However, chronic administration of at least some senolytics in humans can be associated with toxic side effects (Kaefer et al., 2014; Wilson et al., 2010) which may be due to off-target killing of non-senescent cells.”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Wilson et al., 2010
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“In oncology trials, 44–50% of patients experienced grade 3 or 4 thrombocytopenia33,34.”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [33]
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BackgroundInhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesis
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BackgroundABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts
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BackgroundClearance of systemic hematologic tumors by venetoclax (Abt‐199) and navitoclax
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BackgroundBCL2 protein signalling determines acute responses to neoadjuvant chemoradiotherapy in rectal cancer
Flanagan, L., Lindner, A. U., de Chaumont, C., Kehoe, J., Fay, J., Bacon, O., Toomey, S., Huber, H. J., Hennessy, B. T., Kay, E. W., et al. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1221-7 · Cited by 27
“Unfortunately, due to inhibition of BCL(X)L, ABT-737 and ABT-263 are destructive to platelets, leading to dose-limiting thrombocytopenia in patients [41, 42].”
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“Clinical trials involving lymphoid malignancies and small-cell lung cancer have indicated that ABT-263 is promising for some patients (Wilson et al., 2010; Tan et al., 2011).”
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“In phase I clinical trials, ABT-263 displayed a favorable toxicity profile, and its application for a short conditioning therapy seems to be adequate also for nonmalignant conditions.(21) Depleting antibodies—notably more efficient in mice than in humans(42)—are not required, but a blockade of the CD40/CD154 pathway w…”
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Evaluating venetoclax and its potential in treatment-naïve acute myeloid leukemia
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“leukemia (CLL) and small lymphocytic leukemia (SLL)– diseases found to be especially sensitive to the drug.(20)”
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“Unfortunately, current multiple anti-apoptotic protein inhibitors, including those targeting BCL-XL such as navitoclax, are poorly tolerated and have significant side effects [29].”
BackgroundImpact of senolytic treatment on immunity, aging, and disease
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“This latter observation may explain why obatoclax lacks associated thrombocytopenia in patients treated with the drug [29], a common side effect associated with the Bcl-XL antagonist navitoclax [30].”
BackgroundNew therapeutic targets and drugs in non-Hodgkinʼs lymphoma
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“potent in the treatment of some malignancies [11,12].”
BackgroundPROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors
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“However, ABT-263 treatment leads to rapid and dose-dependent thrombocytopenia [37] because platelets depend on BCL-XL to maintain their viability [38, 39].”
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“Notably, other prosurvival molecules like BCL-2 and BCL-XL expression were unchanged by DHA treatment.”
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“We report efficacy at a dose of 6 mg/kg/day—the lowest total dosage reported for inhibitor treatment with BCL2/XLi ABT-263 and/or MCL1i S63845 to date.(10,19,37) For patients, lowering the minimum efficacious dose through innovations in targeted delivery and targeted therapy has the additional benefits of reducing the…”
BackgroundResultCurrent challenges and novel treatment strategies in double hit lymphomas
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“Targeted therapy for DHL Proposed mechanism Preliminary clinical results BCL2 inhibitors Navitoclax Inhibition of BCL2, BCLxL and BCLw 4/4 evaluable patients with R/R DLBCL progressed [Wilson et al. 2010] Venetoclax Selective inhibition of BCL2 28% ORR in R/R DLBCL [Davids et al. 2014]”
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“Although use of antisense oligonucleotides has been challenged with efficient drug delivery issues in clinical trials, significant achievements of non-peptidic small molecule inhibitors (SMI) of antiapoptotic Bcl-2 proteins are ensuring the acceleration of efforts to design Bcl-2 manipulationbased therapeutic approach…”
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Senescent neutrophils: a hidden role in cancer progression
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Using biologic predictive factors to direct therapy of diffuse large B-cell lymphoma
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“Although navitoclax showed efficacy in preclinical trials, thrombocytopenia resulting from inhibition of BCL-XL, a megakaryocyte/platelet pro-survival factor, limited its clinical development [7].”
BackgroundRepurposing BCL-2 and Jak 1/2 inhibitors: Cure and treatment of HIV-1 and other viral infections
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“Pre-clinical data describes the dosage as 150 mg with a half-life of 17 hours and clearance not occurring renally (75, 76).”
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“In a phase I study of relapsed or refractory lymphoid malignancies (including CLL) 22% of patients had partial responses (Wilson et al., 2010), and in a phase I study of relapsed or refractory CLL 35% of patients exhibited partial responses (Roberts et al.”
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“…promising anti-tumor effects, studies had to be discontinued due to dosedependent thrombocytopenia (low levels of platelets) at one hour after administration, which occurs because platelets heavily depend on BCL-xL for their survival (Oltersdorf et al., 2005; Tse et al., 2008; Wilson et al., 2010).”
BackgroundBH3 Mimetics for the Treatment of B-Cell Malignancies—Insights and Lessons from the Clinic
Lin, V. S., Xu, Z., Huang, D. C. S., & Thijssen, R. (2020) · Cancers · doi:10.3390/cancers12113353 · Cited by 24
“However, the development of navitoclax was ultimately curtailed by the dose-limiting thrombocytopenia induced by its on-target inhibition of BCLxL, which platelets rely on for their survival [42,43].”
BackgroundGolla, C., Bilal, M., Dwucet, A., Bader, N., Anthonymuthu, J., Heiland, T., Pruss, M., Westhoff, M., Siegelin, M. D., Capanni, F., et al. (2021) · Cancers · doi:10.3390/cancers13164123 · Cited by 22
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Therapy-induced senescence through the redox lens
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“Thrombocyto-penia for instance, can arise due to the unintended off-target lytic effects on non-senescent cells such as circulating platelets and T lymphocytes since these also rely on Bcl-2 family proteins for survival [123].”
BackgroundGyulkhandanyan, A. V., Mutlu, A., Allen, D. J., Freedman, J. J., & Leytin, V. (2013) · Thrombosis Research · doi:10.1016/j.thromres.2013.10.041 · Cited by 23
“ABT-737 and its analog Navitoclax exhibit antitumor activity and are under clinical trials for treatment of solid tumors and lymphoid malignancies [15,30].”
BackgroundYeast techniques for modeling drugs targeting Bcl-2 and caspase family members
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“In yeast, we found that E1B19K (like DPV022 and SPPV14) was resistant to ABT-737 and ABT-263.”
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“Despite high potency in killing several types of malignant cells in pre-clinical tests, clinical trials of Navitoclax in chronic lymphocytic leukaemia were halted because of platelet toxicity [123].”
BackgroundTargeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies
Mukherjee, N., Sheetz, J., & Shellman, Y. G. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26209859 · Cited by 24
“ABT-263 (Navitoclax) has shown promising efficacy in some clinical trials for hematologic malignancies [60].”
Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice
Avivi, I. M., & Goy, A. H. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0488 · Cited by 21
Therapeutic inhibition of BCL-2 and related family members
Levy, M., & Claxton, D. F. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1290078 · Cited by 20
“published results of a phase I/II trial that is still ongoing with use of ABT-263 in patients with relapsed or refractory lymphoid malignancies [30].”
BackgroundA chemically controlled Cas9 switch enables temporal modulation of diverse effectors
Wei, C. T., Popp, N. A., Peleg, O., Powell, R. L., Borenstein, E., Maly, D. J., & Fowler, D. M. (2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01278-6 · Cited by 21
Pemmaraju, N., Garcia, J. S., Perkins, A. C., Harb, J. G., Souers, A. J., Werner, M. E., Brown, C. M., & Passamonti, F. (2023) · Cancer · doi:10.1002/cncr.34986 · Cited by 22
Therapeutic strategies targeting cellular senescence for cancer and other diseases
Wang, X., Fukumoto, T., & Noma, K.-I. (2024) · The Journal of Biochemistry · doi:10.1093/jb/mvae015 · Cited by 23
“ABT-263 is one of the most potent senolytic agents (105) that exhibits platelet toxicity (107, 108) .”
BackgroundTzakos, A. G., Fokas, D., Johannes, C., Moussis, V., Hatzimichael, E. C., & Briasoulis, E. C. (2011) · Molecules · doi:10.3390/molecules16064408 · Cited by 21
“Navitoclax, a targeted high affinity inhibitor of Bcl-2 has already been evaluated in phase I and Nutlin-3 is currently about to enter early clinical evaluation [59,60].”
BackgroundPlatelet apoptosis and agonist-mediated activation in myelodysplastic syndromes
Jiménez‐Yuste, V., Fernandez-Bello, I., Arias‐Salgado, E. G., Álvarez, M., Martín, M., de Paz, R., & Butta, N. V. (2013) · Thrombosis and Haemostasis · doi:10.1160/th12-09-0670 · Cited by 20
Delbridge, A. R. D., Aubrey, B. J., Hyland, C. D., Bernardini, J. P., Rago, L. D., Garnier, J., Lessène, G., Strasser, A., Alexander, W. S., & Grabow, S. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.304 · Cited by 21
“Furthermore, anaemia is a frequent toxicity associated with cancer therapy, including both conventional chemotherapy as well as emerging targeted therapies, such as some of the BH3-mimetics.(2,3) Understanding the requirements for normal erythroid development and survival will help develop improved treatment strategie…”
BackgroundMulti-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells
Marczyk, M., Patwardhan, G. A., Zhao, J., Qu, R., Li, X., Wali, V. B., Gupta, A. K., Pillai, M. M., Kluger, Y., Yan, Q., et al. (2020) · Cancers · doi:10.3390/cancers12092551 · Cited by 21
“Navitoclax (ABT-263) disrupts protein–protein interactions between the pro-survival proteins, including Bcl-2, Bcl-XL (coded by the BCL2L1 gene) and Bcl-w (coded by the BCL2L2 gene) molecules and the pro-apoptotic family of proteins, leading to unopposed pro-apoptotic signaling [9,10].”
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Discovery and Development of Venetoclax, a Selective Antagonist of BCL ‐2
Fairbrother, W. J., Leverson, J. D., Sampath, D., & Souers, A. J. (2019) · doi:10.1002/9783527814695.ch9 · Cited by 21
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“However, senolytic therapy on premature vascular aging and diabetic cardiovascular complications is rarely reported, and the toxic side effects of senolytic compounds have been reported frequently (Schmid et al. 2014; Walaszczyk et al. 2019; Wilson et al. 2010).”
Appropriate management of molecular subtypes of diffuse large B-cell lymphoma.
Dunleavy, K. M., & Wilson, W. H. (2014) · PubMed · Cited by 20
Self-citationMolecular Targeted Approaches in Mantle Cell Lymphoma
Weniger, M. A., & Wiestner, A. U. (2011) · Seminars in Hematology · doi:10.1053/j.seminhematol.2011.05.001 · Cited by 20
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EWSR1-WT1 Target Genes and Therapeutic Options Identified in a Novel DSRCT In Vitro Model
Bleijs, M., Pleijte, C., Engels, S. A. G., Ringnalda, F. C. A. S., Meyer‐Wentrup, F. A. G., van de Wetering, M., & Clevers, H. C. (2021) · Cancers · doi:10.3390/cancers13236072 · Cited by 20
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Chemogenomics for drug discovery: clinical molecules from open access chemical probes
Quinlan, R. B. A., & Brennan, P. E. (2021) · RSC Chemical Biology · doi:10.1039/d1cb00016k · Cited by 18
Wang, Z., Xu, W., Song, T., Guo, Z., Liu, L., Fan, Y., Wang, A., & Zhang, Z. (2016) · Archiv der Pharmazie · doi:10.1002/ardp.201600251 · Cited by 20
Liu, S., Ren, B. X., Gao, H., Liao, S., Zhai, Y.-X., Li, S., Su, X., Jin, P., Stroncek, D. F., Xu, Z., et al. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1289-2 · Cited by 20
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“Early BH3 mimetics, such as ABT-737 [19] or ABT-263/Navitoclax [20], targeted multiple Early BH3 mimetics, such as ABT-737 [19] or ABT-263/Navitoclax [20], targeted multiple BCL-2 family proteins but had disadvantages such as platelet toxicity [21].”
Novel Targeted Agents in Hodgkin and Non-Hodgkin Lymphoma Therapy
Grover, N. S., & Park, S. I. (2015) · Pharmaceuticals · doi:10.3390/ph8030607 · Cited by 19
“A parallel study in patients with relapsed and refractory lymphoid malignancies showed a durable PR in 10 of 46 patients with a median PFS of 455 days [105].”
BackgroundProgress in BCL2 inhibition for patients with chronic lymphocytic leukemia
Tam, C. S. L., Seymour, J. F., & Roberts, A. W. (2016) · Seminars in Oncology · doi:10.1053/j.seminoncol.2016.02.014 · Cited by 19
Gorombei, P., Guidez, F., Ganesan, S., Chiquet, M., Pellagatti, A., Goursaud, L., Tekin, N., Beurlet, S., Patel, S., Guerenne, L., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910658 · Cited by 20
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“It was found that L2 and C1 show inhibitory potential similar to Navitoclax, while L1 and C2 show lower inhibitory potential when it comes to BCL-2 inhibition.”
MethodJohansson, K. B., Zimmerman, M. S., Dmytrenko, I. V., Gao, F., & Link, D. C. (2023) · Leukemia · doi:10.1038/s41375-023-02057-x · Cited by 19
Cellular senescence: A novel therapeutic target for central nervous system diseases
Lei, S.-Y., Qu, Y., Yang, Y.-Q., Liu, J., Zhang, Y.-F., Zhou, S., He, Q., Jin, H., Yang, Y., & Guo, Z. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117311 · Cited by 21
Drug Resistance and Molecular Cancer Therapy: Apoptosis Versus Autophagy
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Kunami, N., Katsuya, H., Nogami, R., Ishitsuka, K., & Tamura, K. (2014) · PubMed · Cited by 19
Small-Molecule Inhibitors of Protein–Protein Interactions
Liu, Z., Chen, H., Wold, E. A., & Zhou, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12326-1 · Cited by 19
Cell Death Pathways in Lymphoid Malignancies
Fletcher, L. B., Nabrinsky, E., Liu, T., & Danilov, A. V. (2020) · Current Oncology Reports · doi:10.1007/s11912-020-0874-3 · Cited by 20
Structure-Based Design of A-1293102, a Potent and Selective BCL-XL Inhibitor
Tao, Z., Wang, X., Chen, J., Ingram, J. P., Jin, S. S., Judge, R. A., Kovar, P. J., Park, C., Sun, C. C., Wakefield, B. D., et al. (2021) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.1c00162 · Cited by 21
Self-citationYamamoto, M., Sanomachi, T., Suzuki, S., Togashi, K., Sugai, A., Seino, S., Satō, A., Okada, M., & Kitanaka, C. (2021) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdab148 · Cited by 20
Advances in Nanotherapy for Targeting Senescent Cells
Shi, Y., Zhang, Y., Zhang, Y., Yao, J., Guo, J., Xu, X., & Wang, L. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s469110 · Cited by 20
“37 43 D+Q drug therapy for aging has been associated with the development of pulmonary edema.”
BackgroundXu, W., Zhao, T., Chen, H., Huang, N., Gong, H., Zhang, J., Yu, Y., Li, T., Zhang, G., Gong, C., et al. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115045 · Cited by 20
The ageing immune system as a potential target of senolytics
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“Navitoclax targets and inhibits BCL-xL, an anti-apoptotic protein in SnCs that also regulates platelet survival; navitoclax treatment led to grade 3/4 thrombocytopaenia in 29 of 55 lymphoid malignancy patients in an earlier phase I clinical trial [77].”
BackgroundZeng, D., Desai, A. P., Yan, F., Gong, T., Ye, H., Ahmed, M., Nomie, K. J., Romaguera, J. E., Champlin, R. E., Li, S., et al. (2018) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000427 · Cited by 18
Diepstraten, S. T., Chang, C. W. T., Tai, L., Gong, J., Lan, P., Dowell, A. C., Taylor, G. S., Strasser, A., & Kelly, G. L. (2020) · Blood Advances · doi:10.1182/bloodadvances.2019000541 · Cited by 18
“However, on-target toxicity to platelets, which rely on BCL-XL for survival, has stalled the progression of these drugs in clinical trials.(23,24) Recent reports have implicated a role for BCL-W in human cancers.”
BackgroundFrom Bench to Bedside and Beyond: Therapeutic Scenario in Acute Myeloid Leukemia
Gurnari, C., Voso, M. T., Maciejewski, J. P., & Visconte, V. (2020) · Cancers · doi:10.3390/cancers12020357 · Cited by 18
“, involving BCL-XL (B-cell lymphoma-extra large) with consequent side effects such as thrombocytopenia [64].”
BackgroundMasilamani, A. P., Dettmer‐Monaco, V., Monaco, G., Cathomen, T., Kuckuck, I., Schultze-Seemann, S., Huber, N., & Wolf, P. (2020) · Cancers · doi:10.3390/cancers12061648 · Cited by 18
“We used immunotoxin doses shown to be non-toxic in this mouse model [34] and ABT-737 doses which did not elicit thrombocytopenia, which is known to be the most adverse side effect in patients due to platelet dependence on Bcl-xl [52].”
MethodMorimoto, Y., Takada, K., Takeuchi, O., Watanabe, K., Hirohara, M., Hamamoto, T., & Masuda, Y. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03796-6 · Cited by 18
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Interdiction at a protein-protein interface: MCL-1 inhibitors for oncology
Li, K. (2020) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2020.127717 · Cited by 18
Metadata
- Authors
- Wilson, W. H., O'Connor, O. A., Czuczman, M. S., LaCasce, A. S., Gerecitano, J. F., Leonard, J. P., Tulpule, A., Dunleavy, K., Xiong, H., Chiu, Y.-L., Cui, Y., Busman, T., Elmore, S. W., Rosenberg, S. H., Krivoshik, A. P., Enschede, S. H., & Humerickhouse, R. A.
- Affiliations
- National Institutes of Health (US)
- Roswell Park Comprehensive Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- Cornell University (US)
- University of Southern California (US)
- Abbott (United States) (US)
- Corresponding author
- Wilson, Wyndham H
- ORCID
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 11
- Issue
- 12
- Pages
- 1149-1159
- ISSN
- 1470-2045 (ISSN-L)
- PMC
- PMC3025495
- OpenAlex
- W2150680216
- Cited by
- 876
- References
- 47
- Citations by year
- 2026: 44 · 2025: 58 · 2024: 66 · 2023: 49 · 2022: 66 · 2021: 69 · 2020: 70 · 2019: 43 · 2018: 42 · 2017: 53 · 2016: 52 · 2015: 63 · 2014: 60 · 2013: 55 · 2012: 50
- FWCI
- 18.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Abbott Fund
- Abbott Laboratories
- National Institutes of Health
- National Cancer Institute (ZIABC010716)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Keywords
- navitoclax, BCL-2 inhibitor, Bcl-xL, lymphoid malignancies, relapsed/refractory lymphoma, dose-limiting toxicity, thrombocytopenia, neutropenia, anemia, pharmacokinetics, pharmacodynamics, T cell proliferation, platelet function, antitumour activity, intermittent dosing
- MeSH terms
- Aged, Aniline Compounds, Antineoplastic Agents, Blood Platelets, Dosage Forms, Humans, Lymphoma, Middle Aged, Sulfonamides, T-Lymphocytes, Survival Analysis, Drug Delivery Systems, Proto-Oncogene Proteins c-bcl-2, Maximum Tolerated Dose
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