Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.
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Date
2017-05-01ICR Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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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
Publisher
ELSEVIER SCI LTD