Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.
Indian J Cancer
;
2014 Jan-Mar; 51(1): 40-44
Article
in English
| IMSEAR
| ID: sea-154282
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, doselimiting 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 ANDDESIGN:
Phase 1, open-label, dose-escalation study in men and women ≥18 years of age. MATERIALS ANDMETHODS:
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.
Full text:
Available
Index:
IMSEAR (South-East Asia)
Main subject:
Prognosis
/
Sulfones
/
Time Factors
/
Infusions, Intravenous
/
Aged
/
Female
/
Humans
/
Male
/
Tissue Distribution
/
Cohort Studies
Type of study:
Etiology study
/
Incidence study
/
Observational study
/
Prognostic study
/
Risk factors
Language:
English
Journal:
Indian J Cancer
Year:
2014
Type:
Article
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