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Randomized multicenter phase II trial comparing two schedules of etirinotecan pegol (NKTR-102) in women with recurrent platinum-resistant/refractory epithelial ovarian cancer.

AbstractPURPOSE:
Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma.
PATIENTS AND METHODS:
A total of 71 eligible patients were randomly assigned to receive etirinotecan pegol 145 mg/m(2) every 14 or 21 days until progression or unacceptable adverse events (AEs). The primary end point was objective response rate (ORR) by RECIST (version 1.0). Secondary end points included response by Gynecologic Cancer Intergroup criteria, duration of ORR, progression-free survival (PFS), and overall survival (OS).
RESULTS:
The overall confirmed ORR was 20% (95% CI, 10% to 30%): 20% for once every 14 days, and 19% for once every 21 days. Median response duration was 4.1 months for once every 14 days and 4.0 months for once every 21 days. Median PFS for every 14 and every 21 days was 4.1 and 5.3 months, respectively, and median OS was 10.0 and 11.7 months, respectively. Etirinotecan pegol was well tolerated, with the most common grade 3 to 4 AEs being dehydration (24%) and diarrhea (23%). Diarrhea, dehydration, nausea, and neutropenia were less frequent with the schedule of once every 21 days than with that of once every 14 days.
CONCLUSION:
Both schedules of etirinotecan pegol showed activity in patients with heavily pretreated ovarian cancer, with encouraging ORR and PFS rates. The schedule of once every 21 days was better tolerated and had slightly longer PFS and OS rates. The treatment schedule of etirinotecan pegol 145 mg/m(2) once every 21 days was selected for the expanded phase II study and is preferred for future phase III studies. These findings provide support to directly compare etirinotecan pegol versus one of the approved drugs (eg, pegylated liposomal doxorubicin or topotecan) in platinum-resistant ovarian cancer.
AuthorsIgnace B Vergote, Agustin Garcia, John Micha, Charles Pippitt, Johanna Bendell, Daniel Spitz, Nicholas Reed, Graham Dark, Paula M Fracasso, Emad N Ibrahim, Vincent A Armenio, Linda Duska, Chris Poole, Christine Gennigens, Luc Y Dirix, Abraham C F Leung, Carol Zhao, Raoudha Soufi-Mahjoubi, Gordon Rustin
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 32 Pg. 4060-6 (Nov 10 2013) ISSN: 1527-7755 [Electronic] United States
PMID24081946 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
Chemical References
  • Antineoplastic Agents
  • Heterocyclic Compounds, 4 or More Rings
  • Platinum Compounds
  • Polyethylene Glycols
  • etirinotecan pegol
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents (administration & dosage, adverse effects)
  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • Drug Resistance, Neoplasm (drug effects)
  • Female
  • Heterocyclic Compounds, 4 or More Rings (administration & dosage, adverse effects)
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local (drug therapy, mortality)
  • Neoplasms, Glandular and Epithelial (drug therapy, mortality)
  • Ovarian Neoplasms (drug therapy, mortality)
  • Platinum Compounds (therapeutic use)
  • Polyethylene Glycols (administration & dosage, adverse effects)
  • Treatment Outcome

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