Abstract
Background:Eribulin mesylate is a synthetic macrocyclic ketone analogue of Halichondrin B that has demonstrated high antitumor activity in preclinical and clinical settings. This phase I study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics in combination with cisplatin (CP) in patients with advanced solid tumours.Methods:Thirty-six patients with advanced solid tumours received eribulin mesylate 0.7-1.4 mg m<sup>-2</sup> and CP 60-75 mg m<sup>-2</sup>. Eribulin mesylate was administered on days 1, 8, and 15 in combination with CP day 1 every 28-day cycle. The protocol was amended after dose level 4 (eribulin mesylate 1.4 mg m<sup>-2</sup>, CP 60 mg m<sup>-2</sup>) when it was not feasible to administer eribulin mesylate on day 15 because of neutropenia; the treatment schedule was changed to eribulin mesylate on days 1 and 8 and CP on day 1 every 21 days.Results:On the 28-day schedule, three patients had DLT during the first cycle: grade (G) 4 febrile neutropenia (1.0 mg m<sup>-2</sup>, 60 mg m<sup>-2</sup>); G 3 anorexia/fatigue/hypokalemia (1.2 mg m<sup>-2</sup>, 60 mg m<sup>-2</sup>); and G 3 stomatitis/nausea/vomiting/fatigue (1.4 mg m<sup>-2</sup>, 60 mg m<sup>-2</sup>). On the 21-day schedule, three patients had DLT during the first cycle: G 3 hypokalemia/hyponatremia (1.4 mg m<sup>-2</sup>, 60 mg m<sup>-2</sup>); G 4 mucositis (1.4 mg m<sup>-2</sup>, 60 mg m<sup>-2</sup>); and G 3 hypokalemia (1.2 mg m<sup>-2</sup>, 75 mg m<sup>-2</sup>). The MTD and recommended phase II dose was determined as eribulin mesylate 1.2 mg m<sup>-2</sup> (days 1, 8) and CP 75 mg m<sup>-2</sup> (day 1), on a 21-day cycle. Two patients had unconfirmed partial responses (PR) (pancreatic and breast cancers) and two had PR (oesophageal and bladder cancers).Conclusions:On the 21-day cycle, eribulin mesylate 1.2 mg m<sup>-2</sup>, administered on days 1 and 8, in combination with CP 75 mg m<sup>-2</sup>, administered on day 1 is well tolerated and showed preliminary anticancer activity.
Original language | English (US) |
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Pages (from-to) | 2268-2274 |
Number of pages | 7 |
Journal | British Journal of Cancer |
Volume | 111 |
Issue number | 12 |
DOIs | |
State | Published - Dec 9 2014 |
Keywords
- advanced solid tumours
- cisplatin
- eribulin mesylate (E7389)
ASJC Scopus subject areas
- Cancer Research
- Oncology