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Cancer Chemother Pharmacol. 2019 Sep;84(3):567-578. doi: 10.1007/s00280-019-03877-4. Epub 2019 Jun 12.

A phase 1b, multicenter, open-label, dose-finding study of eribulin in combination with carboplatin in advanced solid tumors and non-small cell lung cancer.

Author information

1
Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Road, Bronx, NY, 10461, USA. sgoel@montefiore.org.
2
University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
3
Meenakshi Mission Hospital and Research Center, Madurai, Tamil Nadu, India.
4
Ludwig Boltzmann Institute for Applied Cancer Research and Applied Cancer Research-Institution for Translational Research Vienna, Center for Oncology and Hematology, Kaiser Franz Josef-Spital, Vienna, Austria.
5
Eisai Inc., Woodcliff Lake, NJ, USA.
6
Ruby Hall Clinic, Pune, Maharashtra, India.
7
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
8
Yale University Cancer Center, New Haven, CT, USA.

Abstract

PURPOSE:

This phase 1b study investigated the maximum tolerated dose (MTD; primary objective), safety, pharmacokinetics, and antitumor activity (secondary objectives) of eribulin combined with carboplatin in patients with solid tumors and, in particular, non-small cell lung cancer (NSCLC).

METHODS:

Two dose-escalation schemes were evaluated with carboplatin, at an area under the curve (AUC) of either 5 or 6 mg/mL·min. Eribulin, dose-escalated from 0.7 to 1.4 mg/m2 was administered 1 h before (Schedule A) or after (Schedule B) carboplatin as a 2-5-min bolus infusion on days 1 and 8 of a 21-day cycle. Following tolerability assessment, patients with NSCLC were recruited in an expansion cohort.

RESULTS:

The MTDs were eribulin 1.4 and 1.1 mg/m2 with carboplatin AUC 5 and AUC 6, respectively. The latter combination was used to treat NSCLC patients in the expansion cohort. Pharmacokinetics of eribulin and carboplatin were generally unaffected by administration sequence (i.e., administration of carboplatin did not significantly affect eribulin Cmax and AUC0-t and the converse was also observed). In the NSCLC cohort, the objective response rate was 27%. Median overall and progression-free survival durations were 12.1 and 4.2 months, respectively. No unexpected safety findings were observed.

CONCLUSIONS:

The combination of eribulin and carboplatin demonstrated antitumor activity; however, recent therapeutic advances may be more promising approaches for first-line treatment of NSCLC. Clinical trial registration NCT00268905.

KEYWORDS:

Advanced solid tumors; Eribulin + carboplatin; Maximum tolerated dose; NSCLC; Phase 1b

PMID:
31190276
DOI:
10.1007/s00280-019-03877-4

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