A new approach to integrate toxicity grade ...
Document type :
Compte-rendu et recension critique d'ouvrage
DOI :
Title :
A new approach to integrate toxicity grade and repeated treatment cycles in the analysis and reporting of phase I dose-finding trials
Author(s) :
Doussau, Adélaide [Auteur]
Epidémiologie et Biostatistique [Bordeaux]
Thiebaut, Rodolphe [Auteur]
Statistics In System biology and Translational Medicine [SISTM]
Université de Bordeaux [UB]
Geoerger, B. [Auteur]
Vectorologie et transfert de gènes [VTG / UMR8121]
Schoffski, Patrick [Auteur]
Department of General Medical Oncology [Leuven]
Floquet, Anne [Auteur]
Institut Bergonié [Bordeaux]
Le Deley, M. C. [Auteur]
Département de santé publique
Epidémiologie des cancers : Radiocarcinogénèse et effets iatrogènes des traitements
Mathoulin-Pelissier, S. [Auteur]
Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux
Rizzo, E. [Auteur]
European Organisation for Research and Treatment of Cancer [Bruxelles] [EORTC]
Fumoleau, Pierre [Auteur]
Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] [UNICANCER/CRLCC-CGFL]
Le Tourneau, Christophe [Auteur]
Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
Paoletti, Xavier [Auteur]
Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
Epidémiologie et Biostatistique [Bordeaux]
Thiebaut, Rodolphe [Auteur]
Statistics In System biology and Translational Medicine [SISTM]
Université de Bordeaux [UB]
Geoerger, B. [Auteur]
Vectorologie et transfert de gènes [VTG / UMR8121]
Schoffski, Patrick [Auteur]
Department of General Medical Oncology [Leuven]
Floquet, Anne [Auteur]
Institut Bergonié [Bordeaux]
Le Deley, M. C. [Auteur]
Département de santé publique
Epidémiologie des cancers : Radiocarcinogénèse et effets iatrogènes des traitements
Mathoulin-Pelissier, S. [Auteur]
Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux
Rizzo, E. [Auteur]
European Organisation for Research and Treatment of Cancer [Bruxelles] [EORTC]
Fumoleau, Pierre [Auteur]
Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] [UNICANCER/CRLCC-CGFL]
Le Tourneau, Christophe [Auteur]
Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
Paoletti, Xavier [Auteur]
Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
Journal title :
Annals of Oncology
Pages :
422-428
Publisher :
Elsevier
Publication date :
2015
ISSN :
0923-7534
HAL domain(s) :
Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Santé publique et épidémiologie
Sciences du Vivant [q-bio]/Santé publique et épidémiologie
English abstract : [en]
Background: Safety assessment beyond the dose-limiting toxicity evaluation period provides relevant informationto define the recommended phase II dose (RP2D) of a new treatment. We retrospectively analyzed three phase I ...
Show more >Background: Safety assessment beyond the dose-limiting toxicity evaluation period provides relevant informationto define the recommended phase II dose (RP2D) of a new treatment. We retrospectively analyzed three phase I trials toillustrate two indicators: per-cycle probability of graded toxicity and cumulative probability of severe toxicity over thetreatment period.Patients and methods: Data were collected from two continual reassessment method (CRM) trials (T1: aviscumine insolid tumors with short time on treatment; T2: erlotinib + radiotherapy in brainstem gliomas with longer time on treatment)and one 3 + 3 design (T3: liposomal doxorubicin + cyclophosphamide combination in ovarian carcinoma). The probabilityof severe and moderate or severe toxicity per cycle was estimated at each dose level with mixed proportional oddsmodel. The cumulative probability of severe toxicity was also estimated with the time-to-event CRM.Results: Eighty-three patients were included in the three trials; 94, 96 and 72 treatment cycles were administered, in T1,T2 and T3, respectively. Moderate toxicities were at least twice as frequent as severe toxicities. An increased probability oftoxicity over time was detected in T3 [P = 0.04; per-cycle probability of severe toxicity: 27% (cycle 1) to 59% (cycle 6) at theRP2D]. At the RP2D, 37% of patients experienced at least one severe toxicity over the first six cycles in T2, and 78% in T3.Conclusions: Dedicated methods can be used to analyze toxicities from all cycles of treatment. They do not delay accrualand should be integrated in the analysis and reporting of phase I dose-finding trials.Show less >
Show more >Background: Safety assessment beyond the dose-limiting toxicity evaluation period provides relevant informationto define the recommended phase II dose (RP2D) of a new treatment. We retrospectively analyzed three phase I trials toillustrate two indicators: per-cycle probability of graded toxicity and cumulative probability of severe toxicity over thetreatment period.Patients and methods: Data were collected from two continual reassessment method (CRM) trials (T1: aviscumine insolid tumors with short time on treatment; T2: erlotinib + radiotherapy in brainstem gliomas with longer time on treatment)and one 3 + 3 design (T3: liposomal doxorubicin + cyclophosphamide combination in ovarian carcinoma). The probabilityof severe and moderate or severe toxicity per cycle was estimated at each dose level with mixed proportional oddsmodel. The cumulative probability of severe toxicity was also estimated with the time-to-event CRM.Results: Eighty-three patients were included in the three trials; 94, 96 and 72 treatment cycles were administered, in T1,T2 and T3, respectively. Moderate toxicities were at least twice as frequent as severe toxicities. An increased probability oftoxicity over time was detected in T3 [P = 0.04; per-cycle probability of severe toxicity: 27% (cycle 1) to 59% (cycle 6) at theRP2D]. At the RP2D, 37% of patients experienced at least one severe toxicity over the first six cycles in T2, and 78% in T3.Conclusions: Dedicated methods can be used to analyze toxicities from all cycles of treatment. They do not delay accrualand should be integrated in the analysis and reporting of phase I dose-finding trials.Show less >
Language :
Anglais
Popular science :
Non
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