A randomized phase II study of biweekly irinotecan monotherapy or a combination of irinotecan plus 5-fluorouracil/leucovorin (mFOLFIRI) in patients with metastatic gastric adenocarcinoma refractory to or progressive after first-line chemotherapy
Tóm tắt
The aim of this study was to evaluate the efficacy of irinotecan (CPT-11) monotherapy and CPT-11 plus 5-fluorouracil (5-FU)/leucovorin (LV) combination (mFOLFIRI) as second-line treatment in patients with advanced gastric cancer (AGC). A total of 59 patients were randomly assigned to either CPT-11 (150 mg/m2 iv on day 1) or mFOLFIRI (CPT-11 150 mg/m2 plus LV 20 mg/m2 on day 1 followed by 5-FU 2,000 mg/m2 over 48 h), every 2 weeks. The primary end point was objective response rate (ORR). Following random assignment, 29 patients received CPT-11 and 30 patients mFOLFIRI. The ORR was 17.2 % [95 % confidence interval (CI) 3.4–30.9] and 20.0 % (95 % CI 5.6–34.3) for the CPT-11 and mFOLFIRI arms, respectively (P = 0.525). There was no significant difference in median progression-free survival: 2.2 months (95 % CI 0.2–4.3) for CPT-11 versus 3.0 months (95 % CI 2.0–3.7) for mFOLFIRI (P = 0.481) or in median overall survival: 5.8 months (95 % CI 3.0–8.7), compared with 6.7 months (95 % CI 5.3–8.2) (P = 0.514). Grade 3/4 toxicity was observed in 21 and 28 events in the CPT-11 and mFOLFIRI arms, respectively. Although this study had a small sample size and limited statistical power, CPT-11 monotherapy and mFOLFIRI appear to be equally active and tolerable as second-line chemotherapy for AGC. The addition of 5-FU/LV to CPT-11 did not significantly improve efficacy.
Tài liệu tham khảo
Shin HR, Jung KW, Won YJ, Park JG (2004) 2002 annual report of the Korea Central Cancer Registry: based on registered data from 139 hospitals. Cancer Res Treat 36:103–114
Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M (1993) Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72:37–41
Pyrhonen S, Kuitunen T, Nyandoto P, Kouri M (1995) 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
Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE (2010) Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev: CD004064
Ohtsu A, Yoshida S, Saijo N (2006) Disparities in gastric cancer chemotherapy between the East and West. J Clin Oncol 24:2188–2196
Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24:4991–4997
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376:687–697
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358:36–46
Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI (2009) Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 20:666–673
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221
Wesolowski R, Lee C, Kim R (2009) Is there a role for second-line chemotherapy in advanced gastric cancer? Lancet Oncol 10:903–912
Kanat O, Evrensel T, Manavoglu O, Demiray M, Kurt E, Gonullu G, Kiyici M, Arslan M (2003) Single-agent irinotecan as second-line treatment for advanced gastric cancer. Tumori 89:405–407
Futatsuki K, Wakui A, Nakao I, Sakata Y, Kambe M, Shimada Y, Yoshino M, Taguchi T, Ogawa N (1994) Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group. Gan To Kagaku Ryoho 21:1033–1038
Chun JH, Kim HK, Lee JS, Choi JY, Lee HG, Yoon SM, Choi IJ, Ryu KW, Kim YW, Bae JM (2004) Weekly irinotecan in patients with metastatic gastric cancer failing cisplatin-based chemotherapy. Jpn J Clin Oncol 34:8–13
Assersohn L, Brown G, Cunningham D, Ward C, Oates J, Waters JS, Hill ME, Norman AR (2004) Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma. Ann Oncol 15:64–69
Kim ST, Kang WK, Kang JH, Park KW, Lee J, Lee SH, Park JO, Kim K, Kim WS, Jung CW, Park YS, Im YH, Park K (2005) Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane- and cisplatin-refractory, metastatic gastric cancer. Br J Cancer 92:1850–1854
Sym SJ, Ryu MH, Lee JL, Chang HM, Kim TW, Lee SS, Lee JS, Kang YK (2008) Salvage chemotherapy with biweekly irinotecan, plus 5-fluorouracil and leucovorin in patients with advanced gastric cancer previously treated with fluoropyrimidine, platinum, and taxane. Am J Clin Oncol 31:151–156
Ajani JA, Baker J, Pisters PW, Ho L, Mansfield PF, Feig BW, Charnsangavej C (2002) Irinotecan/cisplatin in advanced, treated gastric or gastroesophageal junction carcinoma. Oncology 16:16–18
Park SH, Choi EY, Bang SM, Cho EK, Lee JH, Shin DB, Ki Lee W, Chung M (2005) Salvage chemotherapy with irinotecan and cisplatin in patients with metastatic gastric cancer failing both 5-fluorouracil and taxanes. Anticancer Drugs 16:621–625
Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P (2011) Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer–a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 47:2306–2314
(1992) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project. J Clin Oncol 10:896–903
Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355:1041–1047
Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343:905–914
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216
Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29:3968–3976
Takiuchi H (2011) Second-line chemotherapy for gastric cancer: a new issue lies ahead in global trials. Gastric Cancer 14:206–211
Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH (2012) Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 30:1513–1518
Catalano V, Graziano F, Santini D, D’Emidio S, Baldelli AM, Rossi D, Vincenzi B, Giordani P, Alessandroni P, Testa E, Tonini G, Catalano G (2008) Second-line chemotherapy for patients with advanced gastric cancer: who may benefit? Br J Cancer 99:1402–1407