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

Sponsor
National Cancer Center, Korea
Study ID
NCT00874328
Phase
PHASE1/PHASE2
Status
Unknown

Conditions

  • Advanced Non-Small Cell Lung Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
Oct 31, 2008
Status verified
Jul 2010
Primary completion
Dec 31, 2011
Completion
Dec 31, 2012

Study Design

Enrollment
74 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: study arm
    Irinotecan /IV D1 Cisplatin 60mg/m2 iv D1 S-1 bid, P.o. D1 \~ 14 q 3 weeks until maximum 6 cycles

Primary Outcome Measure

Evaluation the Response rate IP plus TS-1(in phase 2) [ Time Frame: 1 year ]

Central Contacts

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