دورية أكاديمية
أعرض في EDS

Patient self-reporting of tolerability using PRO-CTCAE in a randomized double-blind, placebo-controlled phase II trial comparing gemcitabine in combination with adavosertib or placebo in patients with platinum resistant or refractory epithelial ovarian carcinoma.

التفاصيل البيبلوغرافية
العنوان: Patient self-reporting of tolerability using PRO-CTCAE in a randomized double-blind, placebo-controlled phase II trial comparing gemcitabine in combination with adavosertib or placebo in patients with platinum resistant or refractory epithelial ovarian carcinoma.
المؤلفون: Madariaga A; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Autonomous University of Barcelona, Barcelona, Spain., Mitchell SA; National Cancer Institute at the National Institutes of Health, Rockville, USA., Pittman T; Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Wang L; University of Toronto, Toronto, Ontario, Canada; Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Bowering V; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Kavak N; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Quintos J; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Chang K; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Ramsahai J; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Karakasis K; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Welch SA; Division of Medical Oncology & Hematology, London Health Science, London, Ontario, Canada., Dhani NC; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada., Lheureux S; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada., Oza AM; Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address: amit.oza@uhn.ca.
المصدر: Gynecologic oncology [Gynecol Oncol] 2022 Nov; Vol. 167 (2), pp. 226-233. Date of Electronic Publication: 2022 Aug 30.
نوع المنشور: Randomized Controlled Trial; Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 0365304 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-6859 (Electronic) Linking ISSN: 00908258 NLM ISO Abbreviation: Gynecol Oncol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, Academic Press.
مواضيع طبية MeSH: Gemcitabine* , Ovarian Neoplasms*/pathology, Female ; Humans ; Carcinoma, Ovarian Epithelial/drug therapy ; Platinum/therapeutic use ; Fatigue ; Double-Blind Method ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
مستخلص: Background: A double-blind, randomized, placebo-controlled, phase 2 trial assessed gemcitabine in combination with the wee1 inhibitor adavosertib or placebo in platinum resistant or refractory high grade serous ovarian cancer (HGSOC), demonstrating improved progression free and overall survival favouring the adavosertib/gemcitabine arm. An exploratory objective of the study included the PRO-CTCAE assessment, to capture self-reporting of frequency, severity and/or interference of symptomatic adverse events (syAEs).
Methods: PRO-CTCAE items at baseline, days 1 and 15 of each cycle and off treatment, were completed in two centres, with the objective of characterizing syAEs in the first three months of therapy. The maximum post-baseline score proportion for each syAE was tabulated per patient. The 12-week area under the curve (AUC12w) as a measure of syAE over-time and incremental AUC12w (iAUC12w) for adjustment to baseline syAEs.
Results: Sixty-one patients were approached for PRO-CTCAE surveys and 55 were evaluable. Among patients with HGSOC, 28 received gemcitabine/adavosertib (arm A) and 19 gemcitabine/placebo (arm B). Survey completion rates were high. The proportion of participants with positive (≥1) PRO-CTCAE scores was higher for difficulty swallowing with gemcitabine/adavosertib (arm A 35.7% vs arm B 5.3%, p = 0.02). The high score (≥3) syAEs showed more frequent diarrhea with gemcitabine/adavosertib (arm A 25% vs arm B 0%, p = 0.03). The proportions of worsening syAEs over time were higher in patients receiving gemcitabine/adavosertib for difficulty swallowing (arm A 35.7% vs arm B 5.3%; p = 0.03) and fatigue severity (arm A 71.43% vs arm B 42.1%; p = 0.04).
Conclusions: The longitudinal assessment of patient self-reported tolerability showed greater difficulty swallowing and fatigue severity in patients receiving gemcitabine/adavosertib, compared to gemcitabine/placebo. PRO-CTCAE provides complementary and objective assessment of drug tolerability from a patient's perspective.
(Copyright © 2022. Published by Elsevier Inc.)
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معلومات مُعتمدة: UM1 CA186644 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Adavosertib; Gemcitabine; Ovarian cancer; PRO-CTCAE; Patient reported outcomes; clinical trial.
المشرفين على المادة: 0 (Gemcitabine)
K2T6HJX3I3 (adavosertib)
49DFR088MY (Platinum)
تواريخ الأحداث: Date Created: 20220902 Date Completed: 20231023 Latest Revision: 20231221
رمز التحديث: 20231221
مُعرف محوري في PubMed: PMC10731422
DOI: 10.1016/j.ygyno.2022.08.006
PMID: 36055813
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-6859
DOI:10.1016/j.ygyno.2022.08.006