Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199).

Abstract

OBJECTIVE:

HPV infection has been associated with deregulation of the PI3K-Akt-mTOR pathway in invasive cervical carcinomas. This 2-stage phase II study assessed the activity of the mTOR inhibitor, temsirolimus, in patients with measurable metastatic and/or locally advanced, recurrent carcinoma of the cervix.

METHODS:

Temsirolimus 25mg i.v. was administered weekly in 4 week cycles. One response among the first 18 patients was required to proceed to the second stage of accrual. Correlative molecular studies were performed on archival tumor tissue.

RESULTS:

Thirty-eight patients were enrolled. Thirty-seven patients were evaluable for toxicity and 33 for response. One patient experienced a partial response (3.0%). Nineteen patients had stable disease (57.6%) [median duration 6.5 months (range 2.4-12.0mo)]. The 6-month progression free survival rate was 28% (95% CI: 14-43%). The median progression free survival was 3.52 months [95% CI (1.81-4.70)]. Adverse effects were mild-moderate in most cases and similar to other temsirolimus studies. No toxicity>grade 3 was observed. Assessment of PTEN and PIK3CA by IHC, copy number analyses and PTEN promoter methylation status did not reveal subsets associated with disease stability.

CONCLUSION:

Single agent temsirolimus has modest activity in cervical carcinoma with about two-thirds of patients exhibiting stable disease. Molecular markers for treatment benefit remain to be identified.

• Authors: A V Tinker, S Ellard, S Welch, F Moens, G Allo, M S Tsao, J Squire, D Tu, E A Eisenhauer, H MacKay
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 130 Issue 2 Pg. 269-74 (Aug 2013) ISSN: 1095-6859 [Electronic] United States
• PMID: 23672928 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• temsirolimus
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human
• TOR Serine-Threonine Kinases
• PTEN Phosphohydrolase
• PTEN protein, human
• Sirolimus

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Class I Phosphatidylinositol 3-Kinases
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• PTEN Phosphohydrolase (analysis)
• Phosphatidylinositol 3-Kinases (analysis)
• Protein Kinase Inhibitors (therapeutic use)
• Sirolimus (adverse effects, analogs & derivatives, therapeutic use)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)
• Uterine Cervical Neoplasms (drug therapy, mortality)