British journal of cancer · 2015
A phase I combination dose-escalation study of eribulin mesylate and gemcitabine in patients with advanced solid tumours: a study of the Princess Margaret Consortium.
Клиническое исследование I фазыСтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Lheureux S, Oza A M, Laurie S A, Halford R, Jonker D, Chen E, Keller D, Bourade V, Wang L, Doyle L, Siu L L, Goel R
Аннотация
BACKGROUND: Eribulin mesylate is a synthetic microtubule inhibitor that showed cytotoxic synergy in combination with gemcitabine preclinically. This combination was assessed in a Phase I dose-finding trial in patients diagnosed with advanced solid tumours who had received up to two prior chemotherapy regimens for metastatic disease (CP cohort).
METHODS: Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated.
RESULTS: 45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0 mg m(-2) eribulin and 1000 mg m(-2) gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts - 2/21 (CP), 1/10 (G) and 2/14 (CN).
CONCLUSIONS: The combination of eribulin and gemcitabine was well tolerated at the RP2D.
METHODS: Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated.
RESULTS: 45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0 mg m(-2) eribulin and 1000 mg m(-2) gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts - 2/21 (CP), 1/10 (G) and 2/14 (CN).
CONCLUSIONS: The combination of eribulin and gemcitabine was well tolerated at the RP2D.
Предметные рубрики MeSH
AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsDeoxycytidineDisease-Free SurvivalEndometrial NeoplasmsFemaleFuransHumansKetonesMaleMiddle AgedNeoplasm MetastasisNeoplasmsNeutropeniaOntarioOvarian NeoplasmsResponse Evaluation Criteria in Solid TumorsTreatment OutcomeGemcitabinePolyether Polyketides