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Indian J Cancer. 2014 Jan-Mar;51(1):40-4. doi: 10.4103/0019-509X.134617.

Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.

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1
Department of Medical Oncology, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, India.

Abstract

CONTEXT:

Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies.

AIMS:

To determine the safety, dose-limiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD).

SETTINGS AND DESIGN:

Phase 1, open-label, dose-escalation study in men and women ≥18 years of age.

MATERIALS AND METHODS:

An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD).

STATISTICAL ANALYSIS USED:

All data summaries were descriptive. PK parameters were estimated using compartmental analysis.

RESULTS:

25 patients (16 male, 9 female, 26-66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days.

CONCLUSIONS:

2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.

PMID:
24947095
DOI:
10.4103/0019-509X.134617
[Indexed for MEDLINE]
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