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http://ir.nhri.org.tw/handle/3990099045/6135
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| Title: | Phase II study of low-dose everolimus plus weekly cisplatin and 24-hour infusion of high-dose 5-fluorouracil and leucovorin for first-line treatment of metastatic or recurrent gastric cancers |
| Authors: | Yeh, K;Shen, YC;Li, CP;Yen, CJ;Lin, YL;Lin, ZZ;Chen, LT;Su, WC;Chao, Y;Cheng, AL |
| Contributors: | National Institute of Cancer Research |
| Abstract: | Background: Cisplatin-HDFL regimen, using weekly 24-hour infusions of cisplatin and high-dose 5-fluorouracil (5-FU) and leucovorin, is commonly used in Taiwan for patients with advanced gastric cancer (GC), showing a satisfactory response rate with favourable toxicity profiles [J Clin Oncol 1994; 12(4): 875; J Clin Oncol (Suppl) 2006; 24(18S): A14063]. Everolimus (RAD001), a derivative of rapamycin, is an orally bioavailable mTOR inhibitor. We have demonstrated that low-dose everolimus (in concentration of 0.5 to 5.0 nM) has a chemosensitizing effect for cisplatin and 5-FU in GC cells [Proc Am Assoc Cancer Res 2007; 48: A4043]. Methods: All patients had pathologically confirmed metastatic/recurrent chemonaive GC, at least 1 measurable lesion, a fasting serum triglyceride level >70 mg/dl, ECOG PS 0/1/2, adequate hepatic, renal, and bone marrow functions. Everolimus 10 mg PO on days 1, 8, and 15; and was given concurrently with the initiation of chemotherapy. Cisplatin 35 mg/m2 was given as a 24h infusion, days 1 and 8. A 24h infusion of 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 (HDFL) was given on days 1, 8, and 15. Cycles were repeated every 28 days, and response evaluation was performed every 2 cycles & at the end of protocol treatment. The primary end-point was confirmed objective response rate (RR) by RECIST. Results: Between Mar. 2008 and Mar. 2011, 30 patients (M:15, F:15) with a median age of 55 (33?71) were enrolled and evaluable for response assessment. The overall RR was 60.0% (41?77%, 95% C.I.) with one CR and 17 PRs. Among a total of 201 cycles (median: 6, range: 1 to 25 cycles) given, Gr3/4 neutropenia, infection, nausea, and vomiting developed in 4.0%, 2.0%, 2.5%, and 2.5% of 201 cycles, respectively (data cut-off date: Mar. 31, 2011). None of them developed Gr3/4 stomatitis, diarrhea, or skin rash. Gastrointestinal and skin toxicities were generally mild with addition of low-dose weekly everolimus to cisplatin-HDFL. Gr1/2 nausea, vomiting, stomatitis, and diarrhea developed in 18.9%, 15.4%, 12.9%, and 6.0% of 201 cycles, respectively. Gr1/2 skin rash and Gr1 hand-foot syndrome developed in 7.0% and 30.8% of 201 cycles, respectively. One patient has developed reversible HDFL-related hyperammonemic encephalopathy. Median PFS (range: 1.2 to 24.3+ months) and OS (range: 1.8 to 24.3+months) was 7.2 and 12.6 months, respectively. Conclusions: Low-dose everolimus plus infusional cisplatin-HDFL is a highly effective regimen with low toxicity and favorable survival in firstline treatment of metastatic or recurrent GC. Addition of low-dose weekly everolimus to infusional cisplatin and HDFL did not cause any additional gastrointestinal toxicity. |
| Date: | 2011-09 |
| Relation: | European Journal of Cancer. 2011 Sep;47(Suppl 1):S467. |
| Link to: | http://dx.doi.org/10.1016/S0959-8049(11)71896-2 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0959-8049&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000295752801622 |
| Appears in Collections: | [陳立宗] 會議論文/會議摘要
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| ISI000295752801622.pdf | | 44Kb | Adobe PDF | 434 | View/Open |
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