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International Journal of Colorectal Disease

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01-03-2015 | Original Article

Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer

Authors: Ting Jin, Yuan Zhu, Jia-Lin Luo, Ning Zhou, De-Chuan Li, Hai-Xin Ju, Yong-Tian Fan, Yong Liu, Yu-Ping Zhu, Hai-Yang Feng, Lu-Ying Liu

Published in: International Journal of Colorectal Disease | Issue 3/2015

Abstract

Purpose

The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer.

Methods and Materials

Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days −6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m²) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate.

Results

Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %.

Conclusion

These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.

Siegel R, Naishadham D, Jemal A (2013) Cancer statistics. CA Cancer J Clin 63:11–30CrossRefPubMed

Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Briffaux A, Collette L (2005) Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results—EORTC 22921. J Clin Oncol 23:5620–5627CrossRefPubMed

Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC (2006) EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123CrossRefPubMed

Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620–4625CrossRefPubMed

Sauer R, Becker H, Hohenberger W, Rödel 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 (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740CrossRefPubMed

Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358:1160–1174CrossRefPubMed

Kopp R, Rothbauer E, Mueller E, Schildberg FW, Jauch KW, Pfeiffer A (2003) Reduced survival of rectal cancer patients with increased tumor epidermal growth factor receptor levels. Dis Colon Rectum 46:1391–1399CrossRefPubMed

Baumann M, Krause M (2004) Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results. Radiother Oncol 72:257–266CrossRefPubMed

Giralt J, Eraso A, Armengol M, Rosselló J, Majó J, Ares C, Espin E, Benavente S, de Torres I (2002) Epidermal growth factor receptor is a predictor of tumor response in locally advanced rectal cancer patients treated with preoperative radiotherapy. Int J Radiat Oncol Biol Phys 54:1460–1465CrossRefPubMed

10.

Giralt J, de las Heras M, Cerezo L, Eraso A, Hermosilla E, Velez D, Lujan J, Espin E, Rosello J, Majó J, Benavente S, Armengol M, de Torres I, Grupo Español de Investigacion Clinica en Oncologia Radioterápica (GICOR) (2005) The expression of epidermal growth factor receptor results in a worse prognosis for patients with rectal cancer treated with preoperative radiotherapy: a multicenter, retrospective analysis. Radiother Oncol 74:101–108CrossRefPubMed

11.

Azria D, Bibeau F, Barbier N, Zouhair A, Lemanski C, Rouanet P, Ychou M, Senesse P, Ozsahin M, Pèlegrin A, Dubois JB, Thèzenas S 2005 Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer. Bmc Cancer. 5:62

12.

Zhang W, Park DJ, Lu B, Yang DY, Gordon M, Groshen S, Yun J, Press OA, Vallböhmer D, Rhodes K, Lenz HJ (2005) Epidermal growth factor receptor gene polymorphisms predict pelvic recurrence in patients with rectal cancer treated with chemoradiation. Clin Cancer Res 11:600–605PubMed

13.

Li S, Kim JS, Kim JM, Cho MJ, Yoon WH, Song KS, Yeo SG, Kim JS (2006) Epidermal growth factor receptor as a prognostic factor in locally advanced rectal-cancer patients treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys 65:705–712CrossRefPubMed

14.

Kim JS, Kim JM, Li S, Yoon WH, Song KS, Kim KH, Yeo SG, Nam JS, Cho MJ (2006) Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy. Int J Radiat Oncol Biol Phys 66:195–200CrossRefPubMed

15.

Spindler KL, Nielsen JN, Lindebjerg J, Brandslund I, Jakobsen A (2006) Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region. Int J Radiat Oncol Biol Phys 66:500–504CrossRefPubMed

16.

Mateo C, Moreno E, Amour K, Lombardero J, Harris W, Pérez R (1997) Humanization of a mouse monoclonal antibody that blocks the epidermal growth factor receptor: recovery of antagonistic activity. Immunotechnology 3:71–81CrossRefPubMed

17.

Fernandez A, Spitzer E, Perez R, Boehmer FD, Eckert K, Zschiesche W, Grosse R (1992) A new monoclonal antibody for detection of EGF-receptors in western blots and paraffin-embedded tissue sections. J Cell Biochem 49:157–165CrossRefPubMed

18.

Akashi Y, Okamoto I, Iwasa T, Yoshida T, Suzuki M, Hatashita E, Yamada Y, Satoh T, Fukuoka M, Ono K, Nakagawa K (2008) Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status. Br J Cancer 98:749–755CrossRefPubMedCentralPubMed

19.

Crombet-Ramos T, Rak J, Pérez R, Viloria-Petit A (2002) Antiproliferative, antiangiogenic and proapoptotic activity of h-R3: a humanized anti-EGFR antibody. Int J Cancer 101:567–575CrossRefPubMed

20.

Ramakrishnan MS, Eswaraiah A, Crombet T, Piedra P, Saurez G, Iyer H, Arvind AS (2009) Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs 1:41–48CrossRefPubMedCentralPubMed

21.

Ramos TC, Figueredo J, Catala M, González S, Selva JC, Cruz TM, Toledo C, Silva S, Pestano Y, Ramos M, Leonard I, Torres O, Marinello P, Pérez R, Lage A (2006) Treatment of high-grade glioma patients with the humanized anti-epidermal growth factor receptor (EGFR) antibody h-R3: report from a phase I/II trial. Cancer Biol Ther 5:375–379CrossRefPubMed

22.

Ramos TC, Figueredo J, Catala M, González S, Selva JC, Cruz TM, Toledo C, Silva S, Pestano Y, Ramos M, Leonard I, Torres O, Marinello P, Pérez R, Lage A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19–23CrossRef

23.

Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R (2004) German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740CrossRefPubMed

24.

Cividalli A, Ceciarelli F, Livdi E, Altavista P, Cruciani G, Marchetti P, Danesi DT (2002) Radiosensitization by oxaliplatin in a mouse adenocarcinoma: influence of treatment schedule. Int J Radiat Oncol Biol Phys 52:1092–1098CrossRefPubMed

25.

Magné N, Fischel JL, Formento P, Etienne MC, Dubreuil A, Marcié S, Lagrange JL, Milano G (2003) Oxaliplatin-5-fluorouracil and ionizing radiation. Importance of the sequence and influence of p53 status. Oncol(Basel) 64:280–287

26.

Cancer and Leukemia Group B 899011, Ryan DP, Niedzwiecki D, Hollis D, Mediema BE, Wadler S, Tepper JE, Goldberg RM, Mayer RJ (2006) Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: cancer and Leukemia Group B 89901. J Clin Oncol 24:2557–2562CrossRef

27.

Aschele C, Friso ML, Pucciarelli S, Lonardi S, Sartor L, Fabris G, Urso ED, Del Bianco P, Sotti G, Lise M, Monfardini S (2005) A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer. Ann Oncol 16:1140–1146CrossRefPubMed

28.

Fakih MG, Bullarddunn K, Yang GY, Pendyala L, Toth K, Andrews C, Rustum YM, Ross ME, Levea C, Puthillath A, Park YM, Rajput A (2008) Phase II study of weekly intravenous oxaliplatin combined with oral daily capecitabine and radiotherapy with biologic correlates in neoadjuvant treatment of rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 72:650–657CrossRefPubMed

29.

Carraro S, Roca EL, Cartelli C, Rafailovici L, Castillo Odena S, Wasserman E, Gualdrini U, Huertas E, Barugel M, Ballarino G, Rodriguez MC, Masciangioli G (2002) Radiochemotherapy with short daily infusion of low-dose oxaliplatin, leucovorin, and 5-FU in T3-T4 unresectable rectal cancer: a phase II IATTGI study. Int J Radiat Oncol Biol Phys 54:397–402CrossRefPubMed

30.

Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L (2011) Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol 29:2773–2780CrossRefPubMed

31.

Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, German Rectal Cancer Study Group (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13:679–687CrossRefPubMed

32.

Fernández-Martos C, Nogué M, Cejas P, Moreno-García V, Machancoses AH, Feliu J (2012) The role of capecitabine in locally advanced rectal cancer treatment: an update. Drugs 72:1057–1073CrossRefPubMed

33.

Rödel C, Arnold D, Hipp M, Liersch T, Dellas K, Iesalnieks I, Hermann RM, Lordick F, Hinke A, Hohenberger W, Sauer R (2008) Phase I-II trial of cetuximab, capecitabine, oxaliplatin, and radiotherapy as preoperative treatment in rectal cancer. Int J Radiat Oncol Biol Phys 70:1081–1086CrossRefPubMed

34.

Horisberger K, Treschl A, Mai S, Barreto-Miranda M, Kienle P, Ströbel P, Erben P, Woernle C, Dinter D, Kähler G, Hochhaus A, Post S, Willeke F, Wenz F, Hofheinz RD (2009) MARGIT (Mannheimer Arbeitsgruppe für Gastrointestinale Tumoren). Cetuximab in combination with capecitabine, irinotecan, and radiotherapy for patients with locally advanced rectal cancer: results of a phase II MARGIT trial. Int J Radiat Oncol Biol Phys 74:1487–1493CrossRefPubMed

35.

Bertolini F, Chiara S, Bengala C, Antognoni P, Dealis C, Zironi S, Malavasi N, Scolaro T, Depenni R, Jovic G, Sonaglio C, Rossi A, Luppi G, Conte PF (2009) Neoadjuvant treatment with single-agent cetuximab followed by 5-FU, cetuximab, and pelvic radiotherapy: a phase II study in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 73:466–472CrossRefPubMed

36.

Debucquoy A, Haustermans K, Daemen A, Aydin S, Libbrecht L, Gevaert O, De Moor B, Tejpar S, McBride WH, Penninckx F, Scalliet P, Stroh C, Vlassak S, Sempoux C, Machiels JP (2009) Molecular response to cetuximab and efficacy of preoperative cetuximab-based chemoradiation in rectal cancer. J Clin Oncol 27:2751–2757CrossRefPubMed

37.

Kim SY, Hong YS, Kim DY, Kim TW, Kim JH, Im SA, Lee KS, Yun T, Jeong SY, Choi HS, Lim SB, Chang HJ, Jung KH (2011) Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with locally advanced resectable rectal cancer: a multicenter Phase II study. Int J Radiat Oncol Biol Phys 81:677–683CrossRefPubMed

38.

Pinto C, Di Fabio F, Maiello E, Pini S, Latiano T, Aschele C, Garufi C, Bochicchio A, Rosati G, Aprile G, Giaquinta S, Torri V, Bardelli A, Gion M, Martoni A (2011) Phase II study of panitumumab, oxaliplatin, 5-fluorouracil, and concurrent radiotherapy as preoperative treatment in high-risk locally advanced rectal cancer patients (StarPan/STAR-02 Study). Ann Oncol 22:2424–2430CrossRefPubMed

39.

Weiss C, Arnold D, Dellas K, Liersch T, Hipp M, Fietkau R, Sauer R, Hinke A, Rödel C (2010) Preoperative radiotherapy of advanced rectal cancer with capecitabine and oxaliplatin with or without cetuximab: a pooled analysis of three prospective phase I-II trials. Int J Radiat Oncol Biol Phys 78:472–478CrossRefPubMed

40.

Czito BG, Willett CG, Bendell JC, Morse MA, Tyler DS, Fernando NH, Mantyh CR, Blobe GC, Honeycutt W, Yu D, Clary BM, Pappas TN, Ludwig KA, Hurwitz HI (2006) Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results. J Clin Oncol 24:656–662CrossRefPubMed

41.

Machiels JP, Sempoux C, Scalliet P, Coche JC, Humblet Y, Van Cutsem E, Kerger J, Canon JL, Peeters M, Aydin S, Laurent S, Kartheuser A, Coster B, Roels S, Daisne JF, Honhon B, Duck L, Kirkove C, Bonny MA, Haustermans K (2007) Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer. Ann Oncol 18:738–744CrossRefPubMed

42.

Sun PL, Li B, Ye QF (2012) Effect of neoadjuvant cetuximab, capecitabine, and radiotherapy for locally advanced rectal cancer: results of a phase II study. Int J Colorectal Dis 27:1325–1332CrossRefPubMed

43.

Okamoto W, Yoshino T, Takahashi T, Okamoto I, Ueda S, Tsuya A, Boku N, Nishio K, Fukuoka M, Yamamoto N, Nakagawa K (2013) A phase I, pharmacokinetic and pharmacodynamic study of nimotuzumab in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 72:1063–1071CrossRefPubMed

44.

Zhao KL, Hu XC, Wu XH, Fu XL, Fan M, Jiang GL (2012) A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus. Invest New Drugs 30:1585–1590CrossRefPubMed

45.

Choi HJ, Sohn JH, Lee CG, Shim HS, Lee IJ, Yang WI, Kwon JE, Kim SK, Park MS, Lee JH, Kim JH (2011) A phase I study of nimotuzumab in combination with radiotherapy in stages IIB-IV non-small cell lung cancer unsuitable for radical therapy: Korean results. Lung Cancer 71:55–59CrossRefPubMed

46.

Velenik V, Oblak I, Anderluh F 2010 Long-term results from a randomized phase II trial of neoadjuvant combined-modality therapy for locally advanced rectal cancer. Radiat Oncol. 5:88

47.

Rödel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–8696CrossRefPubMed

48.

Eriksen JG, Steiniche T, Overgaard J, Danish Head and Neck Cancer study group (DAHANCA) (2005) The influence of epidermal growth factor receptor and tumor differentiation on the response to accelerated radiotherapy of squamous cell carcinomas of the head and neck in the randomized DAHANCA 6 and 7 study. Radiother Oncol 74:93–100CrossRefPubMed

49.

Wu YL, Liao ML, Qin SK, Sun Y, Zhou CC (2010) Efficacy and safety of Erlotinib in the treatment for advanced non-small cell lung cancer in Chinese patients. Zhonghua Zhong Liu Za Zhi 32:148–151PubMed

50.

Wu YL, Kim JH, Park K, Zaatar A, Klingelschmitt G, Ng C (2012) Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: a subanalysis of the phase III, randomized SATURN study. Lung Cancer-J Iaslc 77:339–345CrossRef

51.

Diaz Miqueli A, Blanco R, Garcia B, Badia T, Batista AE, Alonso R, Montero E (2007) Biological activity in vitro of anti-epidermal growth factor receptor monoclonal antibodies with different affinities. Hybridomas (Larchmt) 26:423–431CrossRef

52.

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 (2007) Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 67:378–384CrossRefPubMed

53.

De Paoli A, Chiara S, Luppi G, Friso ML, Beretta GD, Del Prete S, Pasetto L, Santantonio M, Sarti E, Mantello G, Innocente R, Frustaci S, Corvò R, Rosso R (2006) Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol 17:247–251CrossRef

54.

Das P, Lin EH, Bhatia S, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Hoff PM, Eng C, Wolff RA, Delclos ME, Krishnan S, Janjan NA, Crane CH (2006) Preoperative chemoradiotherapy with capecitabine versus protracted infusion with locally advanced rectal cancer; a matched-pair analysis. Int J Radiat Oncol Biol Phys 66:1378–1383CrossRefPubMed

55.

Dupuis O, Vie B, Lledo G, Hennequin C, Noirclerc M, Bennamoun M, Jacob JH (2007) Preoperative treatment combining capecitabine with radiation therapy in rectal cancer: a GERCOR phase II study. Oncology 73:169–176CrossRefPubMed

56.

Capirci C, Valentini V, Cionini L, De Paoli A, Rodel C, Glynne-Jones R, Coco C, Romano M, Mantello G, Palazzi S, Mattia FO, Friso ML, Genovesi D, Vidali C, Gambacorta MA, Buffoli A, Lupattelli M, Favretto MS, La Torre G (2008) Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: Long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys 72:99–107CrossRefPubMed

57.

Dewdney A, Cunningham D, Tabernero J, Capdevila J, Glimelius B, Cervantes A, Tait D, Brown G, Wotherspoon A, de Castro Gonzalez D, Chua YJ, Wong R, Barbachano Y, Oates J, Chau I (2012) Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol 30:1620–1627CrossRefPubMed

Title: Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer
Authors: Ting Jin
Yuan Zhu
Jia-Lin Luo
Ning Zhou
De-Chuan Li
Hai-Xin Ju
Yong-Tian Fan
Yong Liu
Yu-Ping Zhu
Hai-Yang Feng
Lu-Ying Liu
Publication date: 01-03-2015
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Colorectal Disease / Issue 3/2015
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-014-2097-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer

Abstract

Purpose

Methods and Materials

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods and Materials

Results

Conclusion

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