Safety Study of Capecitabine With Radiation in Elderly Rectal Cancer

Summary

This phase I study is designed to determine the maximum tolerant dose of capecitabine when used in preoperative concurrent chemo-radiation for locally advanced rectal patients over 75 years old.

Timeline

Start

2011-01

Primary completion

2014-05

Completion

2014-05

Publications

• Background Aapro MS, Kohne CH, Cohen HJ, Extermann M. Never too old? Age should not be a barrier to enrollment in cancer clinical trials. Oncologist. 2005 Mar;10(3):198-204. doi: 10.1634/theoncologist.10-3-198.
• Background Papamichael D, Audisio R, Horiot JC, Glimelius B, Sastre J, Mitry E, Van Cutsem E, Gosney M, Kohne CH, Aapro M; SIOG. Treatment of the elderly colorectal cancer patient: SIOG expert recommendations. Ann Oncol. 2009 Jan;20(1):5-16. doi: 10.1093/annonc/mdn532. Epub 2008 Oct 15.
• Background Potosky AL, Harlan LC, Kaplan RS, Johnson KA, Lynch CF. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002 Mar 1;20(5):1192-202. doi: 10.1200/JCO.2002.20.5.1192.
• Background Hemminki K, Santi I, Weires M, Thomsen H, Sundquist J, Bermejo JL. Tumor location and patient characteristics of colon and rectal adenocarcinomas in relation to survival and TNM classes. BMC Cancer. 2010 Dec 21;10:688. doi: 10.1186/1471-2407-10-688.
• Background Janssen-Heijnen ML, Houterman S, Lemmens VE, Louwman MW, Maas HA, Coebergh JW. Prognostic impact of increasing age and co-morbidity in cancer patients: a population-based approach. Crit Rev Oncol Hematol. 2005 Sep;55(3):231-40. doi: 10.1016/j.critrevonc.2005.04.008.
• Background Chang GJ, Skibber JM, Feig BW, Rodriguez-Bigas M. Are we undertreating rectal cancer in the elderly? An epidemiologic study. Ann Surg. 2007 Aug;246(2):215-21. doi: 10.1097/SLA.0b013e318070838f.
• Background Townsley C, Pond GR, Peloza B, Kok J, Naidoo K, Dale D, Herbert C, Holowaty E, Straus S, Siu LL. Analysis of treatment practices for elderly cancer patients in Ontario, Canada. J Clin Oncol. 2005 Jun 1;23(16):3802-10. doi: 10.1200/JCO.2005.06.742.
• Background Ayanian JZ, Zaslavsky AM, Fuchs CS, Guadagnoli E, Creech CM, Cress RD, O'Connor LC, West DW, Allen ME, Wolf RE, Wright WE. Use of adjuvant chemotherapy and radiation therapy for colorectal cancer in a population-based cohort. J Clin Oncol. 2003 Apr 1;21(7):1293-300. doi: 10.1200/JCO.2003.06.178.
• Background Surgery for colorectal cancer in elderly patients: a systematic review. Colorectal Cancer Collaborative Group. Lancet. 2000 Sep 16;356(9234):968-74.
• Background Vulto AJ, Lemmens VE, Louwman MW, Janssen-Heijnen ML, Poortmans PH, Lybeert ML, Coebergh JW. The influence of age and comorbidity on receiving radiotherapy as part of primary treatment for cancer in South Netherlands, 1995 to 2002. Cancer. 2006 Jun 15;106(12):2734-42. doi: 10.1002/cncr.21934.
• Background Devon KM, Vergara-Fernandez O, Victor JC, McLeod RS. Colorectal cancer surgery in elderly patients: presentation, treatment, and outcomes. Dis Colon Rectum. 2009 Jul;52(7):1272-7. doi: 10.1007/DCR.0b013e3181a74d2e.
• Background Law WL, Choi HK, Ho JW, Lee YM, Seto CL. Outcomes of surgery for mid and distal rectal cancer in the elderly. World J Surg. 2006 Apr;30(4):598-604. doi: 10.1007/s00268-005-0442-x.
• Background Endreseth BH, Romundstad P, Myrvold HE, Bjerkeset T, Wibe A; Norwegian Rectal Cancer Group. Rectal cancer treatment of the elderly. Colorectal Dis. 2006 Jul;8(6):471-9. doi: 10.1111/j.1463-1318.2005.00921.x.
• Background Larsen SG, Wiig JN, Tretli S, Giercksky KE. Surgery and pre-operative irradiation for locally advanced or recurrent rectal cancer in patients over 75 years of age. Colorectal Dis. 2006 Mar;8(3):177-85. doi: 10.1111/j.1463-1318.2005.00877.x.
• Background Vironen JH, Sainio P, Husa AI, Kellokumpu IH. Complications and survival after surgery for rectal cancer in patients younger than and aged 75 years or older. Dis Colon Rectum. 2004 Jul;47(7):1225-31. doi: 10.1007/s10350-004-0557-4. Epub 2004 May 28.
• Background Barrier A, Ferro L, Houry S, Lacaine F, Huguier M. Rectal cancer surgery in patients more than 80 years of age. Am J Surg. 2003 Jan;185(1):54-7. doi: 10.1016/s0002-9610(02)01120-0.
• Background Rutten H, den Dulk M, Lemmens V, Nieuwenhuijzen G, Krijnen P, Jansen-Landheer M, van de Poll Franse L, Coebergh JW, Martijn H, Marijnen C, van de Velde C. Survival of elderly rectal cancer patients not improved: analysis of population based data on the impact of TME surgery. Eur J Cancer. 2007 Oct;43(15):2295-300. doi: 10.1016/j.ejca.2007.07.009. Epub 2007 Aug 20.
• Background Rutten HJ, den Dulk M, Lemmens VE, van de Velde CJ, Marijnen CA. Controversies of total mesorectal excision for rectal cancer in elderly patients. Lancet Oncol. 2008 May;9(5):494-501. doi: 10.1016/S1470-2045(08)70129-3.
• Background Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, Shepherd LE, Seitz JF, Francini G. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001 Oct 11;345(15):1091-7. doi: 10.1056/NEJMoa010957.
• Background Iwashyna TJ, Lamont EB. Effectiveness of adjuvant fluorouracil in clinical practice: a population-based cohort study of elderly patients with stage III colon cancer. J Clin Oncol. 2002 Oct 1;20(19):3992-8. doi: 10.1200/JCO.2002.03.083.
• Background Sundararajan V, Mitra N, Jacobson JS, Grann VR, Heitjan DF, Neugut AI. Survival associated with 5-fluorouracil-based adjuvant chemotherapy among elderly patients with node-positive colon cancer. Ann Intern Med. 2002 Mar 5;136(5):349-57. doi: 10.7326/0003-4819-136-5-200203050-00007.
• Background Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91. doi: 10.1200/JCO.2006.06.9039.
• Background Pignon T, Horiot JC, Bolla M, van Poppel H, Bartelink H, Roelofsen F, Pene F, Gerard A, Einhorn N, Nguyen TD, Vanglabbeke M, Scalliet P. Age is not a limiting factor for radical radiotherapy in pelvic malignancies. Radiother Oncol. 1997 Feb;42(2):107-20. doi: 10.1016/s0167-8140(96)01861-0.
• Background Preoperative short-term radiation therapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Rectal Cancer Study Group. Cancer. 1990 Jul 1;66(1):49-55. doi: 10.1002/1097-0142(19900701)66:13.0.co;2-1.
• Background Holm T, Rutqvist LE, Johansson H, Cedermark B. Postoperative mortality in rectal cancer treated with or without preoperative radiotherapy: causes and risk factors. Br J Surg. 1996 Jul;83(7):964-8. doi: 10.1002/bjs.1800830725.
• Background Randomized study on preoperative radiotherapy in rectal carcinoma. Stockholm Colorectal Cancer Study Group. Ann Surg Oncol. 1996 Sep;3(5):423-30. doi: 10.1007/BF02305759.
• Background Shahir MA, Lemmens VE, van de Poll-Franse LV, Voogd AC, Martijn H, Janssen-Heijnen ML. Elderly patients with rectal cancer have a higher risk of treatment-related complications and a poorer prognosis than younger patients: a population-based study. Eur J Cancer. 2006 Nov;42(17):3015-21. doi: 10.1016/j.ejca.2005.10.032. Epub 2006 Jun 22.
• Background Lorchel F, Peignaux K, Crehange G, Bosset M, Puyraveau M, Mercier M, Bosset JF, Maingon P. Preoperative radiotherapy in elderly patients with rectal cancer. Gastroenterol Clin Biol. 2007 Apr;31(4):436-41. doi: 10.1016/s0399-8320(07)89407-3.
• Background Fiorica F, Cartei F, Carau B, Berretta S, Sparta D, Tirelli U, Santangelo A, Maugeri D, Luca S, Leotta C, Sorace R, Berretta M. Adjuvant radiotherapy on older and oldest elderly rectal cancer patients. Arch Gerontol Geriatr. 2009 Jul-Aug;49(1):54-9. doi: 10.1016/j.archger.2008.05.001. Epub 2008 Jun 24.
• Background Pasetto LM, Basso U, Friso ML, Pucciarelli S, Agostini M, Rugge M, Sinigaglia G, Lise M, Sotti G, Monfardini S. Determining therapeutic approaches in the elderly with rectal cancer. Drugs Aging. 2007;24(9):781-90. doi: 10.2165/00002512-200724090-00006.
• Background Neugut AI, Fleischauer AT, Sundararajan V, Mitra N, Heitjan DF, Jacobson JS, Grann VR. Use of adjuvant chemotherapy and radiation therapy for rectal cancer among the elderly: a population-based study. J Clin Oncol. 2002 Jun 1;20(11):2643-50. doi: 10.1200/JCO.2002.08.062.
• Background Dobie SA, Warren JL, Matthews B, Schwartz D, Baldwin LM, Billingsley K. Survival benefits and trends in use of adjuvant therapy among elderly stage II and III rectal cancer patients in the general population. Cancer. 2008 Feb 15;112(4):789-99. doi: 10.1002/cncr.23244.
• Background Pasetto LM, Friso ML, Pucciarelli S, Basso U, Falci C, Bortolami A, Toppan P, Agostini M, Rugge M, Serpentini S, Nitti D, Monfardini S. Rectal cancer neoadjuvant treatment in elderly patients. Anticancer Res. 2006 Sep-Oct;26(5B):3913-23.
• Background Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999 Dec 30;341(27):2061-7. doi: 10.1056/NEJM199912303412706.
• Background Lewis JH, Kilgore ML, Goldman DP, Trimble EL, Kaplan R, Montello MJ, Housman MG, Escarce JJ. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003 Apr 1;21(7):1383-9. doi: 10.1200/JCO.2003.08.010.
• Background Ceelen W, Fierens K, Van Nieuwenhove Y, Pattyn P. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: a systematic review and meta-analysis. Int J Cancer. 2009 Jun 15;124(12):2966-72. doi: 10.1002/ijc.24247.
• Background Fiorica F, Cartei F, Licata A, Enea M, Ursino S, Colosimo C, Camma C. Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data. Cancer Treat Rev. 2010 Nov;36(7):539-49. doi: 10.1016/j.ctrv.2010.03.002. Epub 2010 Mar 23.
• Background Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.
• Background Bujko K, Kepka L, Michalski W, Nowacki MP. Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials. Radiother Oncol. 2006 Jul;80(1):4-12. doi: 10.1016/j.radonc.2006.04.012. Epub 2006 May 26.
• Background Wong RK, Tandan V, De Silva S, Figueredo A. Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD002102. doi: 10.1002/14651858.CD002102.pub2.
• Background Roels S, Duthoy W, Haustermans K, Penninckx F, Vandecaveye V, Boterberg T, De Neve W. Definition and delineation of the clinical target volume for rectal cancer. Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1129-42. doi: 10.1016/j.ijrobp.2006.02.050. Epub 2006 Jun 5.
• Background Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. doi: 10.1200/JCO.2002.07.132.
• Background O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994 Aug 25;331(8):502-7. doi: 10.1056/NEJM199408253310803.
• Background Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. doi: 10.1200/JCO.2001.19.21.4097.
• Background Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. doi: 10.1200/JCO.2001.19.8.2282.
• Background Twelves C; Xeloda Colorectal Cancer Group. Capecitabine as first-line treatment in colorectal cancer. Pooled data from two large, phase III trials. Eur J Cancer. 2002 Feb;38 Suppl 2:15-20. doi: 10.1016/s0959-8049(01)00415-4.
• Background Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kroning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schuller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. doi: 10.1056/NEJMoa043116.
• Background Dunst J, Reese T, Sutter T, Zuhlke H, Hinke A, Kolling-Schlebusch K, Frings S. Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol. 2002 Oct 1;20(19):3983-91. doi: 10.1200/JCO.2002.02.049.
• Background Ngan SY, Michael M, Mackay J, McKendrick J, Leong T, Lim Joon D, Zalcberg JR. A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer. Br J Cancer. 2004 Sep 13;91(6):1019-24. doi: 10.1038/sj.bjc.6602106.
• Background Jin J, Li YX, Liu YP, Wang WH, Song YW, Li T, Li N, Yu ZH, Liu XF. A phase I study of concurrent radiotherapy and capecitabine as adjuvant treatment for operable rectal cancer. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):725-9. doi: 10.1016/j.ijrobp.2005.08.017. Epub 2005 Oct 19.
• Background Kim DY, Jung KH, Kim TH, Kim DW, Chang HJ, Jeong JY, Kim YH, Son SH, Yun T, Hong CW, Sohn DK, Lim SB, Choi HS, Jeong SY, Park JG. Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):378-84. doi: 10.1016/j.ijrobp.2006.08.063. Epub 2006 Nov 9.
• Background Ramani VS, Sun Myint A, Montazeri A, Wong H. Preoperative chemoradiotherapy for rectal cancer: a comparison between intravenous 5-fluorouracil and oral capecitabine. Colorectal Dis. 2010 Aug;12 Suppl 2:37-46. doi: 10.1111/j.1463-1318.2010.02323.x.
• Background Feliu J, Escudero P, Llosa F, Bolanos M, Vicent JM, Yubero A, Sanz-Lacalle JJ, Lopez R, Lopez-Gomez L, Casado E, Gomez-Reina MJ, Gonzalez-Baron M. Capecitabine as first-line treatment for patients older than 70 years with metastatic colorectal cancer: an oncopaz cooperative group study. J Clin Oncol. 2005 May 1;23(13):3104-11. doi: 10.1200/JCO.2005.06.035.
• Background Pasetto LM, Monfardini S. The role of capecitabine in the treatment of colorectal cancer in the elderly. Anticancer Res. 2006 May-Jun;26(3B):2381-6.

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Indications