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A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer

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Zaman, Khalil Durando, Xavier Baurain, Jean-François [UCL] Humblet, Yves [UCL] Mazzeo, Filomena [UCL] Machiels, Jean-Pascal [UCL] Bauer, Jean

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250 mg/m(2)/DXR 40 mg/m(2) every 3 weeks for schedule 1 and VFL 120 mg/m(2)/DXR 25 mg/m(2) days 1 and 8 every 3 weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluation.

Document type Article de périodique (Journal article) – Article de recherche – Clinical Trial, Phase I, Journal Article
Access type Accès restreint
Publication date 2011
Language Anglais
Journal information "Breast Cancer Research and Treatment" - Vol. 127, no. 3, p. 689-696 (2011)
Peer reviewed yes
Publisher Springer New York LLC ((United States) New York)
issn 0167-6806
e-issn 1573-7217
Publication status Publié
Affiliations UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
UCL - Unité d'oncologie médicale
UCL - (SLuc) Centre du cancer
UCL - SSS/IREC/SLUC - Pôle St.-Luc
MESH Subject Vinblastine - administration & dosage - adverse effects - analogs & derivatives - pharmacokinetics - therapeutic use ; Middle Aged ; Humans ; Female ; Drug Administration Schedule ; Doxorubicin - administration & dosage - adverse effects - pharmacokinetics - therapeutic use ; Breast Neoplasms - drug therapy ; Antineoplastic Combined Chemotherapy Protocols - adverse effects - therapeutic use ; Aged ; Adult ; Adolescent
Keywords Breast cancer ; Advanced stage ; Vinflunine ; Doxorubicin ; Phase I ; Pharmacokinetics
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Bibliographic reference Zaman, Khalil ; Durando, Xavier ; Baurain, Jean-François ; Humblet, Yves ; Mazzeo, Filomena ; et. al. A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer. In: Breast Cancer Research and Treatment, Vol. 127, no. 3, p. 689-696 (2011)
Permanent URL http://hdl.handle.net/2078.1/88339