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Further reading for A Burrows and others. Systemic treatment and liver transplantation for hepatocellular carcinoma: two ends of the therapeutic spectrum. Lancet Oncol 2004; 5: 409–18. 1 Olweny CL, Toya T, Katongole-Mbidde E, et al. Treatment of + VM 26 + 5-fluorouracil with mAMSA + VM 26 + 5-fluorouracil. hepatocellular carcinoma with Adriamycin: preliminary Oncology 1987; 44: 207–09. communication. Cancer 1975; 36: 1250–57. 25 Falkson G, Cnaan A, Simson IW, et al. A randomized phase II study 2 Vogel CL, Bayley AC, Brooker RJ, et al. A phase II study of of acivicin and 4’deoxydoxorubicin in patients with hepatocellular adriamycin (NSC 123127) in patients with hepatocellular carcinoma carcinoma in an Eastern Cooperative Oncology Group study. from Zambia and the United States. Cancer 1977; 39: 1923–29. Am J Clin Oncol 1990; 13: 510–15. 3 Johnson PJ, Williams R, Thomas H, et al. Induction of remission in 26 Mok TS, Leung TW, Lee SD, et al. A multi-centre randomized phase hepatocellular carcinoma with doxorubicin. Lancet 1978; 1: II study of nolatrexed versus doxorubicin in treatment of Chinese 1006–09. patients with advanced hepatocellular carcinoma. Cancer Chemother 4 Falkson G, Moertel CG, Lavin P, et al. Chemotherapy studies in Pharmacol 1999; 44: 307–11. primary liver cancer: a prospective randomized clinical trial. 27 Ishikawa T, Ichida T, Sugitani S, et al. Improved survival with oral Cancer 1978; 42: 2149–56. administration of enteric-coated tegafur/uracil for advanced stage 5 Olweny CL, Katongole-Mbidde E, Bahendeka S, et al. Further IV-A hepatocellular carcinoma. J Gastroenterol Hepatol 2001; 16: experience in treating patients with hepatocellular carcinoma in 452–59. Uganda. Cancer 1980; 46: 2717–22. 28 Ravry MJ, Omura GA, Bartolucci AA. Phase II evaluation of 6 Williams R, Melia WM. Liver tumours and their management. cisplatin in advanced hepatocellular carcinoma and Clin Radiol 1980; 31: 1–11. cholangiocarcinoma: a Southeastern Cancer Study Group Trial. 7 Melia WM, Johnson PJ, Williams R. Induction of remission in Cancer Treat Rep 1984; 68: 1517–18. hepatocellular carcinoma: a comparison of VP 16 with adriamycin. 29 Falkson CI, Falkson G. A phase II evaluation of clofazimine plus Cancer 1983; 51: 206–10. doxorubicin in advanced, unresectable primary hepatocellular 8 Chlebowski RT, Tong M, Weissman J, et al. Hepatocellular carcinoma. Oncology 1999; 57: 232–35. carcinoma: diagnostic and prognostic features in North American 30 Baker LH, Saiki JH, Jones SE, et al. Adriamycin and 5-fluorouracil patients. Cancer 1984; 53: 2701–06. in the treatment of advanced hepatoma: a Southwest Oncology 9 Choi TK, Lee NW, Wong J. Chemotherapy for advanced Group study. Cancer Treat Rep 1977; 61: 1595–97. hepatocellular carcinoma. Adriamycin versus quadruple 31 Al Idrissi HY, Ibrahim EM, Abdel SA, et al. Primary hepatocellular chemotherapy. Cancer 1984; 53: 401–05. carcinoma in the eastern province of Saudi Arabia: treatment with 10 Falkson G, MacIntyre JM, Schutt AJ, et al. Neocarzinostatin versus combination chemotherapy using 5-fluorouracil, Adriamycin and m-AMSA or doxorubicin in hepatocellular carcinoma. J Clin Oncol mitomycin-C. Hepatogastroenterology 1985; 32: 8–10. 1984; 2: 581–84. 32 Yang TS, Wang CH, Hsieh RK, et al. Gemcitabine and doxorubicin 11 Falkson G, MacIntyre JM, Moertel CG, et al. Primary liver cancer: for the treatment of patients with advanced hepatocellular an Eastern Cooperative Oncology Group Trial. Cancer 1984; 54: carcinoma: a phase I-II trial. Ann Oncol 2002; 13: 1771–78. 970–77. 33 Feun LG, O’Brien C, Molina E, et al. Recombinant leukocyte 12 Colombo M, Tommasini MA, Del Ninno E, et al. Hepatocellular interferon, doxorubicin, and 5FUDR in patients with hepatocellular carcinoma in Italy: report of a clinical trial with intravenous carcinoma: a phase II trial. J Cancer Res Clin Oncol 2003; 129: doxorubicin. Liver 1985; 5: 336–41. 17–20. 13 Sciarrino E, Simonetti RG, Le Moli S, Pagliaro L. Adriamycin 34 Morstyn G, Ihde DC, Eddy JL, et al. Combination chemotherapy of treatment for hepatocellular carcinoma: experience with 109 hepatocellular carcinoma with doxorubicin and streptozotocin. patients. Cancer 1985; 56: 2751–55. Am J Clin Oncol 1983; 6: 547–51. 14 Melia WM, Johnson PJ, Williams R. Controlled clinical trial of 35 Leung TW, Patt YZ, Lau WY, et al. Complete pathological remission doxorubicin and tamoxifen versus doxorubicin alone in is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma. Cancer Treat Rep 1987; 71: 1213–16. hepatocellular carcinoma. Clin Cancer Res 1999; 5: 1676–81. 15 Lai CL, Wu PC, Chan GC, et al. Doxorubicin versus no antitumor 36 Leung TW, Tang AM, Zee B, et al. Factors predicting response and therapy in inoperable hepatocellular carcinoma: a prospective survival in 149 patients with unresectable hepatocellular carcinoma randomized trial. Cancer 1988; 62: 479–83. treated by combination cisplatin, interferon-alpha, doxorubicin and 16 Johnson PJ, Dobbs N, Kalayci C, et al. Clinical efficacy and toxicity 5-fluorouracil chemotherapy. Cancer 2002; 94: 421–27. of standard dose adriamycin in hyperbilirubinaemic patients with 37 Kajanti MJ, Pyrhonen SO. Phase II intravenous study of epirubicin hepatocellular carcinoma: relation to liver tests and with 5-fluorouracil in patients with advanced hepatocellular pharmacokinetic parameters. Br J Cancer 1992; 65: 751–55. carcinoma. Eur J Cancer 1991; 27: 1620–22. 17 Halm U, Etzrodt G, Schiefke I, et al. A phase II study of pegylated 38 Boucher E, Corbinais S, Brissot P, Boudjema K, Raoul JL. liposomal doxorubicin for treatment of advanced hepatocellular Treatment of hepatocellular carcinoma (HCC) with systemic carcinoma. Ann Oncol 2000; 11: 113–14. chemotherapy combining epirubicin, cisplatinum and infusional 18 Hong RL, Tseng YL. A phase II and pharmacokinetic study of 5-fluorouracil (ECF regimen). Cancer Chemother Pharmacol 2002; pegylated liposomal doxorubicin in patients with advanced 50: 305–08. hepatocellular carcinoma. Cancer Chemother Pharmacol 2003; 51: 39 Bobbio-Pallavicini E, Porta C, et al. Epirubicin and etoposide 433–38. combination chemotherapy to treat hepatocellular carcinoma 19 Cheng AL, Yeh KH, Fine RL, et al. Biochemical modulation of patients: a phase II study. Eur J Cancer 1997; 33: 1784–88. doxorubicin by high-dose tamoxifen in the treatment of advanced 40 Gebbia V, Maiello E, Serravezza G, et al. 5-Fluorouracil plus high hepatocellular carcinoma. Hepatogastroenterology 1998; 45: dose levofolinic acid and oral hydroxyurea for the treatment of 1955–60. primary hepatocellular carcinomas: results of a phase II multicenter 20 Kardinal CG, Moertel CG, Wieand HS, et al. Combined study of the Southern Italy Oncology Group (G.O.I.M.). Anticancer doxorubicin and alpha-interferon therapy of advanced Res 1999; 19: 1407–10. hepatocellular carcinoma. Cancer 1993; 71: 2187–90. 41 Joishy SK, Bennett JM, Balasegaram M, et al. Clinical and 21 Lotz JP, Grange JD, Hannoun L, et al. Treatment of unresectable chemotherapeutic study of hepatocellular carcinoma in Malaysia: a hepatocellular carcinoma with a combination of human comparison with African and American patients. Cancer 1982; 50: recombinant alpha-2b interferon and doxorubicin: results of a pilot 1065–69. study. Eur J Cancer 1994; 30: 1319–25. 42 Taieb J, Bonyhay L, Golli L, et al. Gemcitabine plus oxaliplatin for 22 Feun LG, Savaraj N, Hung S, et al. A phase II trial of recombinant patients with advanced hepatocellular carcinoma using two different leukocyte interferon plus doxorubicin in patients with schedules. Cancer 2003; 98: 2664–70. hepatocellular carcinoma. Am J Clin Oncol 1994; 17: 393–95. 43 Ravry MJ, Omura GA, Bartolucci AA, et al. Phase II evaluation of 23 Falkson G, Ryan LM, Johnson LA, et al. A random phase II study of cisplatin in advanced hepatocellular carcinoma and mitoxantrone and cisplatin in patients with hepatocellular cholangiocarcinoma: a Southeastern Cancer Study Group Trial. carcinoma: an ECOG study. Cancer 1987; 60: 2141–45. Cancer Treat Rep 1986; 70: 311–12. 24 Bezwoda WR, Weaving A, Kew M, Derman DP. Combination 44 Okada S, Okazaki N, Nose H, et al. A phase 2 study of cisplatin in chemotherapy of hepatocellular cancer: comparison of adriamycin patients with hepatocellular carcinoma. Oncology 1993; 50: 22–26. Oncology Vol 5 July 2004 http://image.thelancet.com/extras/03oncl1007webfr.pdf 1 For personal use. Only reproduce with permission from The Lancet. 45 Lencioni M, Falcone A, Allegrini G, et al. Oral doxifluridine in in patients with advanced hepatocellular carcinoma. Cancer 2002; advanced hepatocellular carcinoma: a phase II study. Oncology 2000; 94: 3186–91. 59: 204–09. 63 Lin J, Shiu W, Leung WT, et al. Phase II study of high-dose 46 Pazdur R, Moore DF, Bready B, et al. Phase II trial of edatrexate in ifosfamide in hepatocellular carcinoma. Cancer Chemother patients with advanced hepatocellular carcinoma. Ann Oncol 1994; Pharmacol 1993; 31: 338–39. 5: 646–48. 64 O’Reilly EM, Stuart KE, Sanz-Altamira PM, et al. A phase II study 47 Hochster HS, Green MD, Speyer J, et al. 4' Epidoxorubicin of irinotecan in patients with advanced hepatocellular carcinoma. (epirubicin): activity in hepatocellular carcinoma. J Clin Oncol 1985; Cancer 2001; 91: 101–05. 3: 1535–40. 65 Falkson G, Coetzer B, Klaassen DJ. A phase II study of m-AMSA in 48 Pohl J, Zuna I, Stremmel W, Rudi J. Systemic chemotherapy with patients with primary liver cancer. Cancer Chemother Pharmacol epirubicin for treatment of advanced or multifocal hepatocellular 1981; 6: 127–29. carcinoma. Chemotherapy 2001; 47: 359–65. 66 Bukowski RM, Legha S, Saiki J, et al. Phase II trial of m-AMSA in 49 Shiu W, Mok SD, Leung N, et al. Phase 2 study of high dose hepatocellular carcinoma: a Southwest Oncology Group Study. etoposide (VP16-213) in hepatocellular carcinoma. Jpn J Clin Oncol Cancer Treat Rep 1982; 66: 1651–52. 1987; 17: 113–15. 67 Cheng E, Lightdale C, Young C, et al. Phase II trial of (m-AMSA) 50 Yoshino M, Okazaki N, Yoshida T, et al.
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    Jpn J Clin Oncol 2001;31(1)25–29 Intravenous 5-Fluorouracil Versus Oral Doxifluridine as Preoperative Concurrent Chemoradiation for Locally Advanced Rectal Cancer: Prospective Randomized Trials Nam Kyu Kim1, Jin Sik Min1,JeaKunPark1,SeongHyunYun1,JinSilSung2,HyunChulJung3 and Jae Kyung Roh3 Departments of 1Surgery, 2Radiation Oncology and 3Medical Oncology, Yonsei University College of Medicine, Seoul, Korea Received August 14, 2000; accepted November 6, 2000 Background: Preoperative radiation treatment with concomitant intravenous infusion of 5- fluorouracil (5-FU) is known to be effective in shrinking and downstaging of tumors. However, chemotherapy has often been limited by its toxicity and poor patient compliance. Oral 5-FU is known to have several advantages over conventional intravenous 5-FU infusion such as lower toxicity and higher quality of life without compromising the efficacy of the treatment. The aim of this study was to compare intravenous 5-FU with oral doxifluridine with respect to tumor response, toxicity and quality of life. Methods: Twenty-eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998, were included in this study. Intravenous 5-FU (450 mg/m2) and leucovorin (20 mg/m2) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) (n = 14). Oral doxifluridine (700 mg/m2/day) and leucovorin (20 mg/m2) were given daily during radiation treatment (n = 14). Quality of life was scored according to 22 activity items (good, >77; fair, >58; poor, <57). Surgical resection was performed 4 weeks after completion of concurrent chemoradiation treatment.
  • ( 12 ) United States Patent ( 10 ) Patent No .: US 10,945,990 B2 Matsui Et Al

    ( 12 ) United States Patent ( 10 ) Patent No .: US 10,945,990 B2 Matsui Et Al

    USO10945990B2 ( 12 ) United States Patent ( 10 ) Patent No .: US 10,945,990 B2 Matsui et al . ( 45 ) Date of Patent : Mar. 16 , 2021 ( 54 ) COMBINATION OF A PD - 1 ANTAGONIST 7,521,051 B2 4/2009 Collins et al . AND ERIBULIN FOR TREATING CANCER 7,982,060 B2 7/2011 Austad et al . 8,008,449 B2 8/2011 Korman et al . 8,093,410 B2 1/2012 Chase et al . ( 71 ) Applicants :MERCK SHARP & DOHME CORP ., 8,168,757 B2 5/2012 Finnefrock et al . Rahway, NJ ( US ); Eisai R & D 8,350,067 B2 1/2013 Endo et al . Management Co. , Ltd. , Tokyo ( JP ) 8,354,509 B2 1/2013 Carven et al . 8,383,796 B2 2/2013 Korman et al . ( 72 ) Inventors : Junji Matsui , Tsukuba ( JP ) ; Gursel 2011/0271358 Al 11/2011 Freeman et al . Aktan , North Wales, PA ( US ) ; Vassiliki 2015/0246033 A1 * 9/2015 Flynn A61K 31/4709 Karantza , Rahway, NJ (US ) ; RuiRong 424 / 133.1 Yuan , Fort Lee , NJ (US ); Yasuhiro FOREIGN PATENT DOCUMENTS Funahashi , Tsukuba ( JP ) ; Erhan Berrak , River Vale , NJ (US ) CN 103562406 A 2/2014 JP 2002-518384 A 6/2002 JP 2006-340714 A 12/2006 ( 73 ) Assignees : EISAI R & D MANAGEMENT CO . , WO WO - 2004 / 004771 A1 1/2004 LTD ., Tokyo ( JP ) ; MERCK SHARP & WO WO - 2004 / 056875 A1 7/2004 DOHME CORP ., Rahway , NJ ( US ) WO WO - 2004 / 072286 A1 8/2004 WO WO - 2007 / 061874 A2 5/2007 ( * ) Notice : Subject to any disclaimer , the term of this WO WO - 2008 / 156712 A1 12/2008 patent is extended or adjusted under 35 WO WO - 2010 / 027827 A2 3/2010 WO WO - 2010 / 077634 Al 7/2010 U.S.C.