A Pilot Study of Irinotecan Combined with 5-Fluorouracil and Leucovorin for the Treatment of Chinese Patients with Locally Advanced and Metastatic Gastric Cancer
Restricted accessResearch articleFirst published online July, 2009
A Pilot Study of Irinotecan Combined with 5-Fluorouracil and Leucovorin for the Treatment of Chinese Patients with Locally Advanced and Metastatic Gastric Cancer
The FOLFIRI regimen was evaluated for its anti-tumor activity and toxicity in Chinese patients with locally advanced and metastatic gastric cancer.
Methods and study design
Treatment consisted of irinotecan, 180 mg/m2 (90-min infusion), leucovorin, 200 mg/m2 (2-h infusion), followed by 5-fluorouracil, 400 mg/m2 (bolus), and then 5-fluorouracil, 600 mg/m2 (22-h continuous infusion) on days 1 and 2, every 14 days.
Results
Twenty-six patients, of whom 17 were pretreated, were included in the study. Partial response was observed in 9 patients (37.5%). The overall disease control rate was 83.3%. Median progression-free and overall survival was 6.8 and 11.2 months, respectively. Grade 3–4 neutropenia was observed in 6 patients (23.1%) and grade 2–3 diarrhea in 5 (19.2%). No treatment-related deaths occurred.
Conclusions
The results demonstrate that the FOLFIRI regimen is an active regimen with acceptable toxicity for Chinese patients with advanced and metastatic gastric cancer that merits further investigation in comparative trials.
ParkinM., BrayF., FerlayJ., PisaniP.: Global cancer statistics 2002 D. CA Cancer J Clin, 55: 74–108, 2005.
2.
SetiawanV.W., ZhangZ.F., YuG.P., LiY.L., LuM.L., TsaiC.J., CordovaD., WangM.R., GuoC.H., YuS.Z., KurtzR.C.: GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population. Cancer Epidemiol Biomarkers Prevent, 9: 73–80, 2000.
3.
WatersJ.S., NormanA., CunninghamD., ScarffeJ.H., WebbA., HarperP., JoffeJ.K., MackeanM., MansiJ., LeahyM., HillA., OatesJ., RaoS., NicolsonM., HickishT.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: Results of a randomized trial. Br J Cancer, 80: 269–272, 1999.
4.
ChauI., NormanA.R., CunninghamD., WatersJ.S., OatesJ., RossP.J.: Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer—pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol, 22: 2395–2403, 2004.
5.
GlimeliusB., EkstromK., HoffmanK., GrafW., SjödénP.O., HaglundU., SvenssonC., EnanderL.K., LinnéT., SellsrömH., HeumanR.: Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol, 8: 163–168, 1997.
6.
PyrhonenS., KuitunenT., NyandotoP., KouriM.: Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer, 71: 587–591, 1995.
KohneC.H., CataneR., KleinB., DucreuxM., Thuss-PatienceP., NiederleN., GipsM., PreusserP., KnuthA., ClemensM., BugatR., FigerI., ShaniA., FagesB., BettaD.D., JacquesC., WilkeH.J.: Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial. Br J Cancer, 89: 997–1001, 2003.
12.
BokuN., OhtsuA., ShimadaY., ShiraoK., SekiS., SaitoH., SakataY., HyodoI.: Phase II study of a combination of irinotecan and cisplatin against metastatic gastric cancer. J Clin Oncol, 17: 319–323, 1999.
13.
YamaoT., ShiraoK., MatsumuraY., MuroK., YamadaY., GotoM., ChinK., ShimadaY.: Phase I-II study of irinotecan combined with mitomycin-C in patients with advanced gastric cancer. Ann Oncol, 12: 1729–1735, 2001.
14.
YamadaY., YasuiH., GotoA., AraiT., UraT., HamaguchiT., MuroK., ShimadaY., ShiraoK.: Phase I study of irinotecan and S-1 combination therapy in patients with metastatic gastric cancer. Int J Clin Oncol, 8: 374–380, 2003.
15.
BlankeC.D., HallerD.G., BensonA.B., RothenbergM.L., BerlinJ., MoriM., HsiehY.C., MillerL.L.: A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma. Ann Oncol, 12: 1575–1580, 2001.
16.
DouillardJ.Y., CunninghamD., RothA.D., NavarroM., JamesR.D., KarasekP., JandikP., IvesonT., CarmichaelJ., AlaklM., GruiaG., AwadL., RougierP.: Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet, 355: 1041–1047, 2000.
17.
AndreT., LouvetC., Maindrault-GoebelF., CouteauC., MabroM., LotzJ.P., Gilles-AmarV., KrulikM., CarolaE., IzraelV., de GramontA.: CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. Eur J Cancer, 35: 1343–1347, 1999.
18.
InnocentiF., RatainM.J.: Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology (Williston Park), 17: 52–55, 2003.
19.
BeutlerE., GelbartE., DeminaA.: Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promote: a balanced polymorphism for regulation of bilirubin metabolism?Proc Natl Acad Sci USA, 95: 8170–8174, 1998.
20.
AkabaK., KimuraT., SasakiA., TanabeS., IkegamiT., HashimotoM., UmedaH., YoshidaH., UmetsuK., ChibaH.: Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese. Biochem Mol Biol Int, 46: 21–26, 1998.
21.
ArmitageJ.O., CarboneP.P., ConnorsJ.M., LevineA., BennetJ.M., KrollS.Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients. J Clin Oncol, 21: 897–906, 2003.
22.
PozzoC., BaroneC., SzantoJ., PadiE., PeschelC., BükkiJ., GorbunovaV., ValvereV., ZaluskiJ., BiakhovM., ZuberE., JacquesC., BugatR.: Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol, 15: 1773–1781, 2004.
23.
BouchéO., RaoulJ.L., BonnetainF., GiovanniniM., EtienneP.L., LledoG., ArsèneD., PaitelJ.F., Guérin-MeyerV., MitryE., BuecherB., KaminskyM.C., SeitzJ.F., RougierP., BedenneL., MilanC.: Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Fédération Francophone de Cancérologie Digestive Group Study—FFCD 9803. J Clin Oncol, 22: 4319–4328, 2004.
24.
KimS.G., OhS.Y., KwonH.C., LeeS., KimJ.H., KimS.H., KimH.J.: A phase II study of irinotecan with bi-weekly, low-dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as salvage therapy for patients with advanced or metastatic gastric cancer. Jpn J Clin Oncol, 37: 744–749, 2007.
25.
O'DwyerP.J., CatalanoR.B.: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy. J Clin Oncol, 24: 4534–4538, 2006.
26.
OnoueM., KuritaA., KadoS., MatsumotoT., KanedaN., UchidaK., KatoI., YokokuraT.: Involvement of UDP-glucuronosyltransferase activity inirinotecan-induced delayed-onset diarrhea in rats. Cancer Chemother Pharmacol, 61: 595–605, 2008.
27.
HanJ.Y., LimH.S., ShinE.S., YooY.K., ParkY.H., LeeJ.E., JangI.J., LeeD.H., LeeJ.S.: Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol, 24: 2237–2244, 2006.
28.
RammohanM., JeevananthineeJ., ZhouQ.Y., TanE.H., SparreboomA., VerweijJ., BalramC.: The influence of functional polymorphisms in UGT1A7 and UGT1A9 on irinotecan pharmacokinetics in Asian cancer patients. J Clin Oncol, 23: 2007, 2005.
29.
AzrakR.G., CaoS., SlocumH.K., TóthK., DurraniF.A., YinM., PendyalaL., ZhangW., McLeodH.L., RustumY.M.: Therapeutic synergy between irinotecan and 5-fluorouracil against human tumor xenografts. Clin Cancer Res, 10: 1121–1129, 2004.
