Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study
Open accessAbstract
Background CI-994, an oral histone deacetylase inhibitor, has antineoplastic activity and synergism with gemcitabine preclinically. This randomized phase II trial explored whether CI-994 plus gemcitabine improves overall survival, objective response, duration of response, time to treatment failure and change in quality of life (QoL) or pain compared with gemcitabine alone. Patients and methods A total of 174 patients received CG (CI-994 6 mg/m(2)/day days 1-21 plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 each 28-day cycle) or PG (placebo plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 of each 28-day cycle days 1-21). Results Median survival was 194 days (CG) versus 214 days (PG) (P = 0.908). The objective response rate with CG was 12% versus 14% with PG when investigator-assessed and 1% versus 6%, respectively, when assessed centrally. Time to treatment failure did not differ between the two arms (P = 0.304). QoL scores at 2 months were worse with CG than with PG. Pain response rates were similar between the two groups. There was an increased incidence of neutropenia and thrombocytopenia with CG. Conclusions Adding CI-994 to gemcitabine in advanced pancreatic carcinoma does not improve overall survival, response rate or time to progression; CG produced decreased QoL and increased hematological toxicity and appears inferior to single-agent gemcitabine.
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CI-994 has undergone phase II clinical trials for advanced pancreatic cancer, nonsmall cell lung cancer and multiple myeloma, and phase III clinical trials in combination with gemcitabine for advanced nonsmall-cell lung and pancreatic cancers (discontinued).
“CI-994 has undergone phase II clinical trials for advanced pancreatic cancer, nonsmall cell lung cancer and multiple myeloma [18–20], and has been in phase III clinical trials in combination with gemcitabine for advanced nonsmall-cell lung and pancreatic cancers, though this trial was discontinued [20].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [18]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredCI-994 is well tolerated and has undergone phase II/III clinical trials for several types of cancer.
“Importantly, CI-994 is well tolerated and has undergone phase II/III clinical trials for several types of cancer [18–20].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [18]
The Introduction (page unavailable) says CI-994 was well tolerated in a small pancreatic-cancer trial and describes phase II trials in several cancer types. It does not report a phase III trial of CI-994; the phase III study listed in the References concerns gemcitabine and fluorouracil, not CI-994. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCI-994 has undergone phase II/III clinical trials for several types of cancer.
“CI-994 is well tolerated and has undergone phase II/III clinical trials for several types of cancer [18–20].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [18]
The Introduction reports phase II trials of CI-994 in pancreatic, non-small-cell lung, head and neck, and renal cell cancers; it also describes CI-994 as well tolerated in the pancreatic trial. It does not report a phase III trial of CI-994, so the phase III part of the attributed claim is unsupported. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCI-994 is well tolerated.
“CI-994 is well tolerated and has undergone phase II/III clinical trials for several types of cancer [18–20].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [18]
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- original article Annals of Oncology
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Adhikari, N., Jha, T., & Ghosh, B. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01676 · Cited by 74 · see citing works
Lu, W., Kawatani, K., Ren, Y., Nambara, T., Jia, L., Jeevaratnam, S., Lee, E., Martinez, P. R., Izhar, T., Wang, N., et al. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-01982-0 · Cited by 4 · see citing works
- Authors
- Richards, D. A., Boehm, K. A., Waterhouse, D. M., Wagener, D. J., Krishnamurthi, S. S., Rosemurgy, A., Grove, W., Macdonald, K., Gulyas, S., Clark, M., & Dasse, K. D.
- Affiliations
- Oncology Hematology Care (US)
- University Hospitals of Cleveland (US)
- University of South Florida (US)
- Pfizer (United States) (US)
- Corresponding author
- Richards, D.A.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 17
- Issue
- 7
- Pages
- 1096-1102
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2140942363
- Cited by
- 101
- References
- 1
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 6 · 2021: 7 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 7 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 6
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- gemcitabine, CI-994, histone deacetylase inhibitors, advanced pancreatic cancer, combination chemotherapy, overall survival, quality of life, pain, hematologic toxicity, neutropenia, thrombocytopenia
- MeSH terms
- Gemcitabine, Adenocarcinoma, Aged, Antimetabolites, Antineoplastic, Antineoplastic Combined Chemotherapy Protocols, Benzamides, Deoxycytidine, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Phenylenediamines, Prognosis, Survival Rate
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