Randomized controlled trial testing the efficacy of platinum-free interval prolongation in advanced ovarian cancer: The MITO-8,MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study

S. Pignata, G. Scambia, A. Bologna, S. Signoriello, I.B. Vergote, U. Wagner, D. Lorusso, V. Murgia, R. Sorio, G. Ferrandina, C. Sacco, G. Cormio, E. Breda, S. Cinieri, D. Natale, G. Mangili, C. Pisano, S.C. Cecere, M. Di Napoli, V. SalutariF. Raspagliesi, L. Arenare, A. Bergamini, J. Bryce, G. Daniele, M.C. Piccirillo, C. Gallo, F. Perrone

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm(median, 7.8 v 0.01 months). Therewas no OS benefit in the experimental arm(median, 21.8 v 24.5 months; hazard ratio, 1.38; 95% CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95% CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting.
Original languageEnglish
Pages (from-to)3347-3353
Number of pages7
JournalJournal of Clinical Oncology
Volume35
Issue number29
DOIs
Publication statusPublished - 2017

Keywords

  • carboplatin
  • doxorubicin
  • gemcitabine
  • paclitaxel
  • topotecan
  • trabectedin
  • 1,3 dioxolane derivative
  • antineoplastic agent
  • deoxycytidine
  • macrogol derivative
  • tetrahydroisoquinoline derivative
  • adult
  • advanced cancer
  • adverse outcome
  • aged
  • allergy
  • alopecia
  • anemia
  • anorexia
  • Article
  • bleeding
  • cancer combination chemotherapy
  • clinical outcome
  • constipation
  • controlled study
  • desquamation
  • diarrhea
  • drug efficacy
  • eye disease
  • fatigue
  • female
  • heart arrhythmia
  • heart disease
  • human
  • human tissue
  • infection
  • lung disease
  • major clinical study
  • metabolic disorder
  • mucosa inflammation
  • multicenter study
  • musculoskeletal disease
  • nausea
  • neuropathy
  • neutropenia
  • open study
  • ovary cancer
  • overall survival
  • pain
  • perception deafness
  • phase 3 clinical trial
  • priority journal
  • progression free survival
  • prospective study
  • quality of life
  • randomized controlled trial
  • rash
  • sensory neuropathy
  • side effect
  • urogenital tract disease
  • vascular disease
  • vomiting
  • analogs and derivatives
  • clinical trial
  • disease course
  • disease free survival
  • drug administration
  • early termination of clinical trial
  • Europe
  • Kaplan Meier method
  • middle aged
  • mortality
  • Ovarian Neoplasms
  • pathology
  • time factor
  • treatment outcome
  • tumor recurrence
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Carboplatin
  • Deoxycytidine
  • Dioxoles
  • Disease Progression
  • Disease-Free Survival
  • Doxorubicin
  • Drug Administration Schedule
  • Early Termination of Clinical Trials
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Paclitaxel
  • Polyethylene Glycols
  • Prospective Studies
  • Tetrahydroisoquinolines
  • Time Factors
  • Topotecan
  • Treatment Outcome

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