The DOI matches its Crossref record; 38 of the 39 references it cites were found in a registry or an index.
Phase I Study of Navitoclax (ABT-263), a Novel Bcl-2 Family Inhibitor, in Patients With Small-Cell Lung Cancer and Other Solid Tumors
Open accessAbstract
Purpose: Resistance to chemotherapy-induced apoptosis represents a major obstacle to cancer control. Overexpression of Bcl-2 is seen in multiple tumor types and targeting Bcl-2 may provide therapeutic benefit. A phase I study of navitoclax, a novel inhibitor of Bcl-2 family proteins, was conducted to evaluate safety, pharmacokinetics, and preliminary efficacy in patients with solid tumors. Patients and Methods: Patients enrolled to intermittent dosing cohorts received navitoclax on day −3, followed by dosing on days 1 to 14 of a 21-day cycle. Patients on continuous dosing received a 1-week lead-in dose of 150 mg followed by continuous daily administration. Blood samples were collected for pharmacokinetic analyses, biomarker analyses, and platelet monitoring. Results: Forty-seven patients, including 29 with small-cell lung cancer (SCLC) or pulmonary carcinoid, were enrolled between 2007 and 2008, 35 on intermittent and 12 on continuous dosing cohorts. Primary toxicities included diarrhea (40%), nausea (34%), vomiting (36%), and fatigue (34%); most were grade 1 or 2. Dose- and schedule-dependent thrombocytopenia was seen in all patients. One patient with SCLC had a confirmed partial response lasting longer than 2 years, and eight patients with SCLC or carcinoid had stable disease (one remained on study for 13 months). Pro-gastrin releasing peptide (pro-GRP) was identified as a surrogate marker of Bcl-2 amplification and changes correlated with changes in tumor volume. Conclusion: Navitoclax is safe and well tolerated, with dose-dependent thrombocytopenia as the major adverse effect. Preliminary efficacy data are encouraging in SCLC. Efficacy in SCLC and the utility of pro-GRP as a marker of treatment response will be further evaluated in phase II studies.
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In the citing paper
“clinical trial data suggest that the dose-limiting toxicities of obatoclax may preclude sufficient target inhibition, in contrast to ABT-263 (30, 34, 35).”
From mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1 (2014) · cites this paper as [30]
Experimental — accuracy not yet measuredIn the citing paper
“The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
In the citing paper
“Bcl-xl inhibition with ABT263 and other small molecular inhibitors induces platelet apoptosis and results in severe thrombocytopenia, which prevents the use of ABT263 and other Bcl-xl specific inhibitors in the clinic—even for cancer patients—because platelets solely depend on Bcl-xl for survival24–27.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
In the citing paper
“Because both SCs and platelets, but not NCs, are primarily dependent on Bcl-xl for survival16–18,24–27 (Supplementary Fig. 1h), we evaluated the effects of PZ compared with ABT263 on the viability of WI38 NCs (Fig. 1g, left panel), IR-SCs (Fig. 1g, middle panel), and platelets (Fig. 1g, right panel).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
In the citing paper
“As reported, ABT263 was highly toxic to both WI38 IR-SCs (Fig. 1g, middle panel) and platelets16–18,24–27 (Fig. 1g, right panel; Supplementary Fig. 2).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
In the citing paper
“Therefore, PZ can selectively induce apoptosis in SCs, but not platelets, which are dependent on Bcl-xl for survival while having minimal toxicity to NCs that are less sensitive to Bcl-xl inhibition than SCs16–18,24–27.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
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Citations
Cites
2 retracted
Pardo, O. E., Arcaro, A., Salerno, G., Raguz, S., Downward, J., & Seckl, M. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.a115.109006 · Cited by 153
RetractedPardo, O. E., Arcaro, A., Salerno, G., Raguz, S., Downward, J., & Seckl, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109006200 · Cited by 145
RetractedAn inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407
ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor
Tse, C., Shoemaker, A. R., Adickes, J., Anderson, M. G., Chen, J., Jin, S., Johnson, E. F., Marsh, K. C., Mitten, M. J., Nimmer, P., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5836 · Cited by 1,992
Certo, M. V., Moore, V. D. G., Nishino, M., Wei, G., Korsmeyer, S. J., Armstrong, S. A., & Letai, A. G. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.027 · Cited by 1,278
van Delft, M. F., Wei, A. H., Mason, K. D., Vandenberg, C. J., Chen, L., Czabotar, P. E., Willis, S. N., Scott, C. L., Day, C. L., Cory, S., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.08.027 · Cited by 1,271
Programmed Anuclear Cell Death Delimits Platelet Life Span
Mason, K. D., Carpinelli, M. R., Fletcher, J. I., Collinge, J. E., Hilton, A. A., Ellis, S., Kelly, P. N., Ekert, P. G., Metcalf, D., Roberts, A. W., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.037 · Cited by 1,031 · cited 1×
“This is a mechanism-based toxicity induced by inhibition of Bcl-xL in circulating platelets,(13,18) which is required for platelet survival.(19,20) Here we describe a phase I dose-escalation study to evaluate the safety (with particular attention to platelet dynamics), pharmacokinetics, and preliminary efficacy of nav…”
BackgroundThe role of Bcl-2 family members in tumorigenesis
Kirkin, V., Joos, S., & Zörnig, M. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2003.08.009 · Cited by 567
Some practical improvements in the continual reassessment method for phase I studies
Goodman, S. N., ZAHURAK, M. L., & Piantadosi, S. (1995) · Statistics in Medicine · doi:10.1002/sim.4780141102 · Cited by 475
Bcl-2 family proteins are essential for platelet survival
Zhang, H., Nimmer, P. M., Tahir, S. K., Chen, J., Fryer, R. M., Hahn, K. R., Iciek, L. A., Morgan, S. J., Nasarre, M. C., Nelson, R., et al. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402081 · Cited by 427
Research works printed but not linked: 2
- Ben-Ezra JM, 1994, Am J Pathol, 145, 1036
- Brambilla E, 1996, Am J Pathol, 149, 1941
Cited by
Sorted by citations
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S. L., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3048 · Cited by 3,058
Self-citationFrom basic apoptosis discoveries to advanced selective BCL-2 family inhibitors
Ashkenazi, A., Fairbrother, W. J., Leverson, J. D., & Souers, A. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.253 · Cited by 903
Broad targeting of resistance to apoptosis in cancer
Mohammad, R. M., Muqbil, I., Lowe, L. J., Yedjou, C. G., Hsu, H.-Y., Lin, L., Siegelin, M. D., Fimognari, C., Kumar, N. B., Dou, Q. P., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.03.001 · Cited by 897
Basu, A. B., Bodycombe, N. E., Cheah, J. H., Price, E. V., Liu, K., Schaefer, G. I., Ebright, R. Y., Stewart, M. L., Ito, D., Wang, S. Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.003 · Cited by 828
Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia
Pan, R. A., Hogdal, L. J., Benito, J. M., Bucci, D. M., Han, L., Borthakur, G. M., Cortes, J. E., DeAngelo, D. J., Debose, L., Mu, H. H., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0609 · Cited by 734
Metadata
- Authors
- Gandhi, L., Camidge, D. R., Ribeiro de Oliveira, M., Bonomi, P., Gandara, D., Khaira, D., Hann, C. L., McKeegan, E. M., Litvinovich, E., Hemken, P. M., Dive, C., Enschede, S. H., Nolan, C., Chiu, Y.-L., Busman, T., Xiong, H., Krivoshik, A. P., Humerickhouse, R., Shapiro, G. I., & Rudin, C. M.
- Affiliations
- Rush University Medical Center (US)
- From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2011-03-01
- Volume
- 29
- Issue
- 7
- Pages
- 909-916
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC4668282
- OpenAlex
- W2119316461
- Cited by
- 603
- References
- 39
- Citations by year
- 2026: 35 · 2025: 28 · 2024: 30 · 2023: 34 · 2022: 32 · 2021: 37 · 2020: 39 · 2019: 29 · 2018: 33 · 2017: 31 · 2016: 40 · 2015: 46 · 2014: 57 · 2013: 54 · 2012: 51
- FWCI
- 24.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- National Cancer Institute (P30CA006973)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- navitoclax, BCL-2 inhibitor, small cell lung cancer, bronchial carcinoid, thrombocytopenia, progastrin-releasing peptide, apoptosis resistance, pharmacokinetics, safety and tolerability, intermittent dosing, continuous dosing, surrogate markers
- MeSH terms
- Administration, Oral, Aged, Aged, 80 and over, Aniline Compounds, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Neoplasms, Prognosis, Sulfonamides, Survival Analysis, Treatment Outcome, Risk Assessment, Genes, bcl-2, Maximum Tolerated Dose, Small Cell Lung Carcinoma
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