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Cited by 125Hepatocellular Carcinoma Treatment and PrognosisPI3K/AKT/mTOR signaling in cancerColorectal Cancer Treatments and Studies

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Phase I/II study of temsirolimus for patients with unresectable Hepatocellular Carcinoma (HCC)- a correlative study to explore potential biomarkers for response

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Yeo, Winnie, Chan, Stephen L, Mo, Frankie KF, Chu, Cheuk M, Hui, Joyce WY, Tong, Joanne HM, Chan, Anthony WH, Koh, Jane, Hui, Edwin P, Loong, Herbert, Lee, Kirsty, Li, Leung, Ma, Brigette, To, Ka F, Yu, Simon CH·2015·BMC Cancer
DOI 10.1186/s12885-015-1334-6PMC PMC4434865
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Abstract

BACKGROUND: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in HCC. Data on the mTOR inhibitor, temsirolimus, is limited in HCC patients with concomitant chronic liver disease. The objectives of this study were: (1) In phase I, to determine DLTs and MTD of temsirolimus in HCC patients with chronic liver disease; (2) In phase II, to assess activity of temsirolimus in HCC, and (3) to explore potential biomarkers for response. METHODS: Major eligibility criteria included histologically confirmed advanced HCC and adequate organ function. In Phase I part of the study, temsirolimus was given weekly in 3-weekly cycle; dose levels were 20 mg (level 1), 25 mg (level 2) and 30 mg (level 3). The MTD was used in the subsequent phase II part; the primary endpoint was PFS and secondary endpoints were response and OS. In addition, exploratory analysis was conducted on pre-treatment tumour tissues to determine stathmin, pS6, pMTOR or p-AKT expressions as potential biomarkers for response. Overall survival and PFS were calculated using the Kaplan-Meier method. Reassessment CT scans were done every 6 weeks. All adverse events were reported using CTCAE v3. RESULTS: The Phase I part consisted of 19 patients, 2 of 6 patients at level 3 experienced DLT; dose level 2 was determined to be the MTD. The phase II part consisted of 36 patients. Amongst 35 assessable patients, there were 1 PR, 20 SD and 14 PD. Overall, the median PFS was 2.83 months (95% C.I. 1.63-5.24). The median OS was 8.89 months (95% C.I. 5.89-13.30). Grade ≥ 3 that occurred in > 10% of patients included thrombocytopenia (4) and hyponatraemia (4). Exploratory analysis revealed that disease stabilization (defined as CR + PR + SD > 12 weeks) in tumours having high and low pMTOR H-scores to be 70% and 29% respectively (OR 5.667, 95% CI 1.129-28.454, p = 0.035). CONCLUSIONS: In HCC patients with chronic liver disease, the MTD of temsirolimus was 25 mg weekly in a 3-week cycle. The targeted PFS endpoint was not reached. However, further studies to identify appropriate patient subgroup are warranted. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov (Id: NCT00321594) on 1 December 2010.

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  • Hydrazides hold a remarkable advantage over hydroxamates-avoidance of glucuronidation in phase II metabolism.

    “Hydrazides hold a remarkable advantage over hydroxamates—avoidance of glucuronidation in phase II metabolism [75, 76].”

    From Medicinal chemistry advances in targeting class I histone deacetylases (2023) · cites this paper as [76]

    The Methods (Treatment plan) and Results (Phase I and II) describe temsirolimus dosing and toxicities in patients with hepatocellular carcinoma; the Discussion addresses its efficacy. Searches for hydrazides, hydroxamates, and glucuronidation found no passage comparing their phase II metabolism. The available copy provides no support for the attributed claim. (LLM, conf=0.78)

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Sorted by citations

  • Medicinal chemistry advances in targeting class I histone deacetylases

    Abdallah, D. I., de Araujo, E. D., Patel, N. H., Hasan, L. S., Moriggl, R., Krämer, O. H., & Gunning, P. T. (2023) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2023.00166 · Cited by 17

    “Typically, UDPglucuronosyl transferases (UGTs) transfer a glucuronide unit onto a hydroxyl unit to tag it for excretion in phase II metabolism (Figure 13), which was observed with the FDA-approved drug belinostat in clinical trials [75, 77].”
    Background

Metadata

Authors
Yeo, W., Chan, S. L., Mo, F. K., Chu, C. M., Hui, J. W., Tong, J. H., Chan, A. W., Koh, J., Hui, E. P., Loong, H., Lee, K., Li, L., Ma, B., To, K. F., & Yu, S. C.
Affiliations
Chinese University of Hong Kong (HK)
Corresponding author
Yeo, Winnie
ORCID
Venue
BMC Cancer
Publisher
Springer Science and Business Media LLC
Published
2015-05-12
Volume
15
Issue
1
Pages
395-395
ISSN
1471-2407 (ISSN-L)
DOI
10.1186/s12885-015-1334-6
PMC
PMC4434865
OpenAlex
W1608382470
Cited by
125
References
4
Citations by year
2026: 2 · 2025: 8 · 2024: 8 · 2023: 9 · 2022: 17 · 2021: 23 · 2020: 24 · 2019: 13 · 2018: 10 · 2017: 7 · 2016: 4
FWCI
4.15
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Cancer (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Pfizer
  • Chinese University of Hong Kong
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords
temsirolimus, hepatocellular carcinoma, mTOR inhibitors, chronic liver disease, PI3K/AKT/mTOR pathway, treatment response biomarkers, phosphorylated mTOR, stathmin, pS6, pAKT, maximum tolerated dose, dose-limiting toxicity, progression-free survival, overall survival, stable disease, thrombocytopenia, hyponatremia
MeSH terms
Adult, Aged, Antineoplastic Agents, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Treatment Outcome, Disease-Free Survival, Sirolimus, Maximum Tolerated Dose, Kaplan-Meier Estimate

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