NCT00874328

A Study of TS-1 Plus Irinotecan and Cisplatin (IP) for Patients With Stage IIIB/IV Non Small Cell Lung Cancer (NSCLC)

A Phase I/II Study of TS-1, Irinotecan and Cisplatin for Patients With Advanced or Metastatic NSLC

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Sponsor: National Cancer Center, Korea · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The irinotecan and cisplatin combination showed significant anti-tumor activity. In the first-line setting, the investigators showed that this regimen had significant anti-tumor activity in 47% of chemo-naïve NSCLC patients with 1-year survival rate of 64.2%. Again, the investigators showed that the second-line Irinotecan and cisplatin is an active and well-tolerated regimen in patients with advanced NSCLC pretreated with non-platinum based chemotherapy. TS-1 (Jeil Pharmaceutical Co.,Ltd, Seoul, Korea) is an oral anticancer drug comprised of tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate, in a molar ratio of 1:0.4:1. Tegafur is a prodrug that generates 5-fluorouracil (5-FU) in blood via metabolism by liver enzyme, and 5-chloro-2, 4-dihydroxypyridine enhance the serum concentration of 5-FU by the competitive inhibition of dihydropyrimidine dehydrogenase, an enzyme responsible for 5-FU catabolism. Potassium oxonate is also a reversible competitive inhibitor of orotate phosphoribosyl transferase, a phosphoenzyme for 5-FU. Diarrhea induced by 5-FU administration is though to be attributable to the phosphorylation of 5-FU by the enzyme in the gastrointestinal tissue. After oral administration of potassium oxonate, the concentration of potassium in the gastrointestinal tissue is high enough to inhibit the enzyme while the concentration in blood and tumor is reported to be either slight or nil. Because of these mechanism, oral TS-1 administration generates a higher concentration of 5-FU than protracted intravenous infusion of 5-FU given in a dose equimolar to the tegafur in S-1, whereas the incidence of adverse events concerning the GI tract does not increase. In a phase II trial of TS-1 as first-line setting in NSCLC, the response rate was 22% and the median survival time was 10.2 months. As expected, the incidence of severe gastrointestinal adverse events was low, and so was few severe hematologic toxicity. Recently 3-weekly TS-1 plus cisplatin showed activity against NSCLC with a response rate of 32.7% and the safety was acceptable.

Detailed description

The investigators are conducting a phase I/II study to determine the maximum-tolerated dose, the recommended dose, and to evaluate the response rate and toxicity of the TS-1, irinotecan and cisplatin combination in patients with advanced or metastatic NSCLC.

Conditions

• Advanced Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Irinotecan	Irinotecan iv D1 q 3 weeks until maximum 6 cycles
DRUG	Cisplatin	cisplatin 60mg/m2 iv D1 q 3weeks until maximum 6 cycles
DRUG	TS-1 (S-1)	TS-1 po D1\~D14 q 3 weeks until maximum 6 cycles

Timeline

• Start date: 2008-10-01
• Primary completion: 2011-12-01
• Completion: 2012-12-01
• First posted: 2009-04-02
• Last updated: 2010-10-25

Locations

1 site across 1 country: South Korea