Publications Repository

Publications Repository

View item 
  •   Home
  • ICR Divisions
  • Cancer Therapeutics
  • View item
  • Home
  • ICR Divisions
  • Cancer Therapeutics
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

Thumbnail
View/Open
Accepted version (438.3Kb)
Date
2017-05
ICR Author
Gore, Martin
Banerji, Udai
De Bono, Johann
Lopez, Juanita
Yap, Timothy
Molife, Rhoda
Banerjee, Susana
Turner, Lydia
Marsden,
Kaye, Stanley Bernard
Show allShow less
Author
George, A
Kristeleit, R
Rafii, S
Michie, CO
Bowen, R
Michalarea, V
van Hagen, T
Wong, M
Rallis, G
Molife, LR
Lopez, J
Banerji, U
Banerjee, SN
Gore, ME
de Bono, JS
Kaye, SB
Yap, TA
Show allShow less
Type
Journal Article
Metadata
Show full item record
Abstract
Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010. A total of 200 AOC patients with progressive disease were allocated to ≥1 trial each, with a total of 281 allocations. Of these, 135 (68%) patients commenced ≥1 trial (mean 1.4 [1-8]), totaling 216 allocated trials; 65 (32%) patients did not start due to deterioration resulting from rapidly progressive disease (63 patients) or patient choice (2 patients). Response Evaluation Criteria in Solid Tumours (RECIST) complete/partial responses (CR/PR) were observed in 43 (20%) of those starting trials, including those on poly(ADP-ribose) polymerase (PARP) inhibitors (18/79 [23%]), antiangiogenics (9/65 [14%]) and chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR included: fewer prior treatments, platinum-sensitive disease, CR/PR with prior therapy, (the United States-based) Eastern Cooperative Oncology Group (ECOG) performance status score, fewer metastatic sites, higher albumin and haemoglobin levels, lower white cell counts and baseline CA125 levels, germline BRCA1/2 mutations and better RMH Prognostic Score. Mean survival was 32° months for patients who achieved CR/PR. Treatments were generally well tolerated. Most patients with AOC (134/200 [67%]) received ≥1 subsequent line of therapy after phase I trials. Our data suggest that phase I trial referrals should be considered earlier in the AOC treatment pathway and before the onset of rapid disease progression particularly with the emergence of promising novel agents in the era of precision medicine.
URI
https://repository.icr.ac.uk/handle/internal/632
DOI
https://doi.org/10.1016/j.ejca.2017.01.020
Collections
  • Cancer Therapeutics
  • Clinical Studies
  • Closed Research Teams
Subject
Humans
Carcinosarcoma
Adenocarcinoma, Clear Cell
Carcinoma, Endometrioid
Neoplasms, Cystic, Mucinous, and Serous
Granulosa Cell Tumor
Ovarian Neoplasms
Neoplasm Metastasis
Serum Albumin
Hemoglobins
Membrane Proteins
Antineoplastic Agents
CA-125 Antigen
Leukocyte Count
Prognosis
Treatment Outcome
Severity of Illness Index
Survival Rate
Retrospective Studies
Genes, BRCA1
Genes, BRCA2
Adult
Aged
Middle Aged
England
Female
Clinical Trials, Phase I as Topic
Drug Discovery
Hereditary Breast and Ovarian Cancer Syndrome
Research team
Medicine (de Bono Prostate)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Medicine Drug Development Unit (Kaye)
Language
eng
Date accepted
2017-01-25
License start date
2017-05
Citation
European journal of cancer (Oxford, England : 1990), 2017, 76 pp. 52 - 59

Browse

All of ICR repositoryICR DivisionsBy issue dateAuthorsTitlesPublication TypesThis collectionBy issue dateAuthorsTitlesPublication Types
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.