chemoradiotherapy; CPT-11; distant metastases; neoadjuvant; rectal cancer
Abstract :
[en] Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a
<br />regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the
<br />recommended dose of neoadjuvant CPT-11 (three times weekly 90 mgm 2) concomitant to hyperfractionated accelerated
<br />radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of
<br />the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cNþ). Median age was 60 years (range 43–
<br />75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery
<br />with total mesorectal excision (TME) was performed within 1 week (range 2–15 days). The preoperative chemoradiotherapy was
<br />overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2
<br />years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66%
<br />(95% confidence interval 0.48–0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse
<br />remains a concern in this patient population.
Disciplines :
Oncology Hematology
Author, co-author :
Voelter, V; The University of Lausanne Hospitals > Multidisciplinary Oncology Centre
Zouhair, A; The University of Lausanne Hospitals, Lausanne > Radio- Oncology
Vuilleumier, H; The University of Lausanne Hospitals > Surgery
Matter, M; The University of Lausanne Hospitals > Surgery
Bouzourene, H; The University of Lausanne Hospitals, Lausanne > Pathology
Leyvraz
Bauer, J; The University of Lausanne Hospitals > Multidisciplinary Oncology Centre
COUCKE, Philippe ; The University of Lausanne Hospitals > Radiothérapie
Stupp, R
Language :
English
Title :
CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II
Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350: 2343-2351
Bosset J, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier J, Collette L (2005) Preoperative radiation (Preop RT) in rectal cancer: effect and timing of additional chemotherapy (CT) 5-year results of the EORTC 22921 trial. J Clin Oncol, ASCO Annual Meeting Proceedings 23, No. 16S, Part I of II (June 1 Supplement): 3505
Bosset JF, Calais G, Daban A, Berger C, Radosevic-Jelic L, Maingon P, Bardet E, Pierart M, Briffaux A (2004) Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group. Eur J Cancer 40: 219-224
Camma C, Giunta M, Fiorica F, Pagliaro L, Craxi A, Cottone M (2000) Preoperative radiotherapy for resectable rectal cancer: a meta-analysis. JAMA 284: 1008-1015
Cedermark B, Johansson H, Rutqvist LE, Wilking N (1995) The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group. Cancer 75: 2269-2275
Chau I, Allen M, Cunningham D, Tait D, Brown G, Hill M, Sumpter K, Rhodes A, Wotherspoon A, Norman AR, Hill A, Massey A, Prior Y (2003) Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer. Br J Cancer 88: 1017-1024
Chen ZS, Sumizawa T, Furukawa T, Ono K, Tani A, Komatsu M, Akiyama S (1999) An enhanced active efflux of CPT-11 and SN-38 in cisplatin-resistant human KB carcinoma cells. Cancer Lett 138: 13-22
Colorectal Cancer Collaborative Group (2001) Adjuvant radiotherapy for rectal cancer: a systematic overview of 8, 507 patients from 22 randomised trials. Lancet 358: 1291-1304
Coucke PA (1992) Postoperative radiation therapy for rectal cancer: an interim analysis of a prospective, randomized multicenter trial in The Netherlands. Cancer 69: 3016-3017
Coucke PA, Notter M, Stamm B, Matter M, Fasolini F, Schlumpf R, Matzinger O, Bouzourene H, on behalf of all surgeons from public hospitals and private clinics (2006) Preoperative hyperfractionated accelerated radiotherapy (HART) in locally advanced rectal cancer (LARC) immediately followed by surgery. A prospective phase II trial. Radiother Oncol 79: 52-58
Coucke PA, Sartorelli B, Cuttat JF, Jeanneret W, Gillet M, Mirimanoff RO (1995) The rationale to switch from postoperative hyperfractionated accelerated radiotherapy to preoperative hyperfractionated accelerated radiotherapy in rectal cancer. Int J Radiat Oncol Biol Phys 32: 181-188
Dotor E, Navarro M, Vega M, Sánchez-Rovira P, Cervantes A, García J, Suárez M, Aranda E, Asensio D, Garcia A, Instituto Catalán de Oncología, HdL-B, Spain; Hospital Marqués de Valdecilla, Santander, Spain; Hospital Ciudad de Jaén, Jaén, Spain; Hospital Clínico de Valencia, Valencia, Spain; Hospital Ramón y Cajal, Madrid, Spain; Hospital del Mar, Barcelona, Spain; Hospital Reina Sofía, Córdoba, Spain; Prasfarma/Almirall, Barcelona, Spain; Aventis Pharma, S.A., Madrid, Spain (2004) Irinotecan (CPT-11) and 5-fluorouracil (5-FU) concomitantly with preoperative radiotherapy (RT) in patients (pts) with locally advanced resectable rectal cancer. Updated results of a phase II study. J Clin Oncol, ASCO Annual Meeting Proceedings (Post-Meeting Edition) 22: 4179
Engel J, Kerr J, Eckel R, Gunther B, Heiss M, Heitland W, Siewert JR, Jauch KW, Holzel D (2005) Influence of hospital volume on local recurrence and survival in a population sample of rectal cancer patients. Eur J Surg Oncol 31: 512-520
Gerard J, Bonnetain F, Conroy T, Chapet O, Bouche O, Closon-Dejardin M, Untereiner M, Leduc B, Francois E, Bedenne L (2005) Preoperative (preop) radiotherapy (RT) + 5 FU/folinic acid (FA) in T3-4 rectal cancers: results of the FFCD 9203 randomized trial. J Clin Oncol, ASCO Annual Meeting Proceedings 23, No.16S, Part I of II (June 1 Supplement): 3504
Glimelius B, Gronberg H, Jarhult J, Wallgren A, Cavallin-Stahl E (2003) A systematic overview of radiation therapy effects in rectal cancer. Acta Oncol 42: 476-492
Gunderson LL, Russell AH, Llewellyn HJ, Doppke KP, Tepper JE (1985) Treatment planning for colorectal cancer: radiation and surgical techniques and value of small-bowel films. Int J Radiat Oncol Biol Phys 11: 1379-1393
Hofheinz RD, von Gerstenberg-Helldorf B, Wenz F, Gnad U, Kraus-Tiefenbacher U, Muldner A, Hehlmann R, Post S, Hochhaus A, Willeke F (2005) Phase I trial of capecitabine and weekly irinotecan in combination with radiotherapy for neoadjuvant therapy of rectal cancer. J Clin Oncol 23: 1350-1357
Janjan NA, Khoo VS, Rich TA, Evetts PA, Goswitz MS, Allen PK, Skibber JM (1998) Locally advanced rectal cancer: surgical complications after infusional chemotherapy and radiation therapy. Radiology 206: 131-136
Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345: 638-646
Kaplan E, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457-487
Kim NK, Kim MJ, Yun SH, Sohn SK, Min JS (1999) Comparative study of transrectal ultrasonography, pelvic computerized tomography, and magnetic resonance imaging in preoperative staging of rectal cancer. Dis Colon Rectum 42: 770-775
Klautke G, Feyerherd P, Ludwig K, Prall F, Foitzik T, Fietkau R (2005) Intensified concurrent chemoradiotherapy with 5-fluorouracil and irinotecan as neoadjuvant treatment in patients with locally advanced rectal cancer. Br J Cancer 92: 1215-1220
Klautke G, Kirchner R, Hopt U, Fietkau R, University of Rostock R, Germany (2001) Continuous Infusion of 5-FU and Weekly Irinotecan with Concurrent Radiotherapy as Neoadjuvant Treatment for Locally Advanced or Recurrent Rectal Cancer. Proc Am Soc Clin Oncol 20(Part I of II): 140a (Abstr.#555)
Kockerling F, Reymond MA, Altendorf-Hofmann A, Dworak O, Hohenberger W (1998) Influence of surgery on metachronous distant metastases and survival in rectal cancer. J Clin Oncol 16: 324-329
Levine E, Gollins S, Susnerwala S, Haylock B, Saunders M, Myint S, Biswas A, Christie Hospital M, United Kingdom; Glanclwyd Hospital, Glanclwyd, United Kingdom; Royal Preston Hospital, Preston, United Kingdom; Clatterbridge Hospital, Liverpool, United Kingdom (2004) Phase II study of radiotherapy plus concurrent irinotecan (CPT-11) and infusional 5-fluorouracil (5FU) in the treatment of T3-T4 locally advanced inoperable rectal cancer. J Clin Oncol ASCO Annual Meeting Proceedings (Post-Meeting Edition) 22(14S): (July 15 Supplement), 3612
Marijnen C, Peeters K, Putter H, Klein Kranenbarg E, Stiggelbout A, Leer L, Van de Velde C, Group DCC (2005) Long term results, toxicity and quality of life in the TME trial. Gastrointestinal Cancers Symposium ASCO, ASTRO, AGA, SSO, Hollywood, Florida (Abstr.#166)
Marijnen CA, Kapiteijn E, van de Velde CJ, Martijn H, Steup WH, Wiggers T, Kranenbarg EK, Leer JW (2002) Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 20: 817-825
Marijnen CA, Nagtegaal ID, Kapiteijn E, Kranenbarg EK, Noordijk EM, van Krieken JH, van de Velde CJ, Leer JW (2003a) Radiotherapy does not compensate for positive resection margins in rectal cancer patients: report of a multicenter randomized trial. Int J Radiat Oncol Biol Phys 55: 1311-1320
Marijnen CA, Nagtegaal ID, Mulder-Stapel AA, Schrier PI, van de Velde CJ, van Krieken JH, Peltenburg LT (2003b) High intrinsic apoptosis, but not radiation-induced apoptosis, predicts better survival in rectal carcinoma patients. Int J Radiat Oncol Biol Phys 57: 434-443
Mehta VK, Cho C, Ford JM, Jambalos C, Poen J, Koong A, Lin A, Bastidas JA, Young H, Dunphy EP, Fisher G (2003) Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer. Int J Radiat Oncol Biol Phys 55: 132-137
Minsky B, O'Reilly E, Wong D, Sharma S, Paty P, Guillem J, Cohen A, Ilson D, Hollywood E, Semple D, Kleban S, Kelsen D, Saltz L (1999) Daily Low-Dose Irinotecan (CPT-11) Plus Pelvic Irradiation as Preoperative Treatment of Locally Advanced Rectal Cancer. Proc Am Soc Clin Oncol 18: 266a (Abstr.#1023)
Minsky BD, Conti JA, Huang Y, Knopf K (1995) Relationship of acute gastrointestinal toxicity and the volume of irradiated small bowel in patients receiving combined modality therapy for rectal cancer. J Clin Oncol 13: 1409-1416
Mitchell E, Anne P, Fry R, Palazzo J, Hauck W, Fishel R, Goldstein S, Isenberg G, Edmunston T, Curran W, Thomas Jefferson Univ, P, PA (2003) Chemoradiation with CPT-11, 5FU in neoadjuvant treatment of locally advanced or recurrent adenocarcinoma of the rectum: A phase I/II study update. Proc Am Soc Clin Oncol 22: 262 (Abstr.#1052)
Nagtegaal ID, Marijnen CA, Kranenbarg EK, van de Velde CJ, van Krieken JH (2002) Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimeter but two millimeters is the limit. Am J Surg Pathol 26: 350-357
Ngan SY, Burmeister BH, Fisher R, Rischin D, Schache DJ, Kneebone A, MacKay JR, Joseph D, Bell A, Goldstein D (2001) Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys 50: 883-887
NIH consensus conference (1990) Adjuvant therapy for patients with colon and rectal cancer. Jama 264: 1444-1450
Pahlman L, Glimelius B (1990) Pre- or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg 211: 187-195
Rodel C, Grabenbauer GG, Matzel KE, Schick C, Fietkau R, Papadopoulos T, Martus P, Hohenberger W, Sauer R (2000) Extensive surgery after high-dose preoperative chemoradiotherapy for locally advanced recurrent rectal cancer. Dis Colon Rectum 43: 312-319
Rodel C, Grabenbauer GG, Papadopoulos T, Hohenberger W, Schmoll HJ, Sauer R (2003) Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer. J Clin Oncol 21: 3098-3104
Rothenberg ML, Eckardt JR, Kuhn JG, Burris III HA, Nelson J, Hilsenbeck SG, Rodriguez GI, Thurman AM, Smith LS, Eckhardt SG, Weiss GR, Elfring GL, Rinaldi DA, Schaaf LJ, Von Hoff DD (1996) Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 14: 1128-1135
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
Sanfilippo NJ, Crane CH, Skibber J, Feig B, Abbruzzese JL, Curley S, Vauthey JN, Ellis LM, Hoff P, Wolff RA, Brown TD, Cleary K, Wong A, Phan T, Janjan NA (2001) T4 rectal cancer treated with preoperative chemoradiation to the posterior pelvis followed by multivisceral resection: patterns of failure and limitations of treatment. Int J Radiat Oncol Biol Phys 51: 176-183
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 (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351: 1731-1740
Saunders M, Dische S, Barrett A, Harvey A, Griffiths G, Palmar M (1999) Continuous, hyperfractionated, accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer: mature data from the randomised multicentre trial. CHART Steering committee. Radiother Oncol 52: 137-148
Stockholm trial (1996) Randomized study on preoperative radiotherapy in rectal carcinoma. Stockholm Colorectal Cancer Study Group. Ann Surg Oncol 3: 423-430
Suwinski R, Wydmanski J, Pawelczyk I, Starzewski J (2006) A pilot study of accelerated preoperative hyperfractionated pelvic irradiation with or without low-dose preoperative prophylactic liver irradiation in patients with locally advanced rectal cancer. Radiother Oncol May 24 [Epub ahead of print]
Swedish Rectal Cancer Trial (SRCT) (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med 336: 980-987
Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson III AB, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ (2002) Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control - final report of intergroup 0114. J Clin Oncol 20: 1744-1750
Turrisi III AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH (1999) Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340: 265-271
Van Cutsem E, Labianca R, Hossfeld D, Bodoky G, Roth A, Aranda E, Nordlinger B, Assadourian S, Wang K, Cunningham D (2005) Randomized phase III trial comparing infused irinotecan/5-fluorouracil (5-FU)/folinic acid (IF) versus 5-FU/FA (F) in stage III colon cancer patients (pts). (PETACC 3). J Clin Oncol, ASCO Annual Meeting Proceedings 23: 8
Voelter V, Stupp R, Matter M, Gillet M, Bouzourene H, Leyvraz S, Coucke P (2003) Preoperative hyperfractionated accelerated radiotherapy (HART) and concomitant CPT-11 in locally advanced rectal carcinoma: a phase I study. Int J Radiat Oncol Biol Phys 56: 1288-1294
