Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study

Placido, Sabino De; Scambia, Giovanni; Vagno, Giovanni Di; Naglieri, Emanuele; Lombardi, Alessandra; Biamonte, R.; Marinaccio, Marco; Cartenì, Giacomo; Manzione, Luigi; Febbraro, Antonio; Matteis, A. De; Gasparini, Giulia; Valerio, Maria Rosaria; Danese, Saverio; Perrone, Francesco; Lauria, Rossella; Laurentiis, Michelino De; Greggi, Stefano; Gallo, Ciro; Pignata, Sandro

doi:10.1200/jco.2004.09.088

Cited by 150 publications

(58 citation statements)

References 25 publications

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“…We also documented a manageable toxicity profile for docetaxel -irinotecan that reduces neurotoxicity compared to using a higher dose of docetaxel alone although at the expense of increased diarrhoea. However, the recent results of two randomised phase III studies (De Placido et al, 2004;Pfisterer et al, 2005) have failed to demonstrate an improvement in survival with the addition of four cycles of the topoisomerase-I inhibitor topotecan after standard carboplatinpaclitaxel as first-line treatment for EOC. Although the MITO-1 study (De Placido et al, 2004) can be criticised for only effectively assessing the concept of consolidation therapy, as 87% of patients randomised to topotecan or placebo had already obtained a complete response to standard treatment, patients were randomised at registration in the GINECO/AGO-OVAR trial (Pfisterer et al, 2005) and 78% of those randomised to sequential topotecan received this therapy.…”

Section: Discussionmentioning

confidence: 99%

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel–irinotecan as first-line therapy for ovarian cancer

et al. 2005

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The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m À2 (arm A, n ¼ 51) or docetaxel 60 mg m À2 with irinotecan 200 mg m À2 (arm B, n ¼ 49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58 -81%; P ¼ 0.079; arm B 67% (90% CI 55 -78%; P ¼ 0.184)). Median-dose intensities were 485% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3 -4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3 -4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted.

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Section: Discussionmentioning

confidence: 99%

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel–irinotecan as first-line therapy for ovarian cancer

et al. 2005

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“…Because of its favored toxicity profile, the doublet therapy therefore remained the standard of care 13 . In a separate phase iii study examining the utility of topotecan consolidation therapy after standard chemotherapy, findings showed that pfs and os were not significantly affected by that addition, and the trial was concluded to be negative 14 . Interestingly, a recent investigation by Katsumata et al, which compared the efficacy of a dose-dense combination of paclitaxel and carboplatin with the standard combination regimen, showed correlating evidence in the form of a pfs and an os favouring the dose-dense regimen 15 .…”

Section: Pfs and Os In The Setting Of First-line Treatment Of Ovarianmentioning

confidence: 99%

Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective

et al. 2011

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“…Four trials underestimated the actual outcome (A/E ratio of >1.25), Eleven trials were accurate (A/E ratio of 0.75‐1.25), and 5 trials overestimated the outcome (A/E ratio of 0.75) (Table 2). 12, 14, 17, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 The A/E ratios ranged from 0.5 to 1.6, with a mean and median ratio of 1.0 and 1.0, respectively (Fig. 3).…”

Section: Resultsmentioning

confidence: 98%

“…A total of 3 and 7 studies were excluded from the OS15, 23, 29 and PFS17, 36, 38, 42, 43, 44, 45 analyses, respectively. This confirmed a statistically significant difference ( P = .001).…”

Section: Resultsmentioning

confidence: 99%

Estimation of expectedness: Predictive accuracy of standard therapy outcomes in randomized phase 3 studies in epithelial ovarian cancer

Castonguay

Wilson

Díaz-Padilla

et al. 2014

Cancer

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BACKGROUNDThe anticipated clinical outcome of the standard/control arm is an important parameter in the design of randomized phase 3 (RP3) trials to properly calculate sample size, power, and study duration. Changing patterns of care or variation in the study population enrolled may lead to a deviation from the initially anticipated outcome. The authors hypothesized that recent changes in patterns of care in epithelial ovarian cancer (EOC) have led to challenges in correctly estimating the outcome of control groups.METHODSA systematic review of the literature was conducted for RP3 trials of EOC published between January 2000 and December 2010. The expected outcome of the control arm as well as the actual outcome achieved by this cohort was collected and a ratio (actual‐over‐expected ratio) was calculated. The estimation of outcome was deemed accurate if the outcome of the control arm was between 0.75 to 1.25 times the anticipated outcome.RESULTSA total of 35 trials were eligible for analysis. Fifteen trials had survival as the primary endpoint whereas 20 had a progression‐based primary endpoint. In total, 12 of 15 trials with a survival‐based endpoint significantly underestimated the outcome of the control arm, whereas only 4 of 20 trials with a progression‐based endpoint did. Studies with a survival endpoint underestimated outcome more frequently than those with a progression endpoint (P<.001).CONCLUSIONSSurvival of the control arm has frequently been underestimated in recent EOC RP3 trials. This underestimation means that the initial statistical assumptions of these trials may have been inaccurate. Underestimating the outcome of the control arm may result in trials being underpowered to demonstrate the absolute benefit they were designed to show. Cancer 2015;121:413–422. © 2014 American Cancer Society.

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Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study

Abstract: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

Cited by 150 publications

References 25 publications

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel–irinotecan as first-line therapy for ovarian cancer

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel–irinotecan as first-line therapy for ovarian cancer

Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective

Estimation of expectedness: Predictive accuracy of standard therapy outcomes in randomized phase 3 studies in epithelial ovarian cancer

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