A novel therapeutic strategy of personalized medicine based on anti-epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer

Matsuhashi,Nobuhisa; Takahashi,Takao; Matsui,Satoshi; Tanahashi,Toshiyuki; Imai,Hisashi; Tanaka,Yoshihiro; Yamaguchi,Kazuya; Yoshida,Kazuhiro

doi:10.3892/ijo.2018.4322

A novel therapeutic strategy of personalized medicine based on anti-epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer

Authors:
- Nobuhisa Matsuhashi
- Takao Takahashi
- Satoshi Matsui
- Toshiyuki Tanahashi
- Hisashi Imai
- Yoshihiro Tanaka
- Kazuya Yamaguchi
- Kazuhiro Yoshida
View Affiliations

Affiliations: Department of Surgical Oncology, Gifu University School of Medicine, Gifu 501-1194, Japan
Published online on: March 16, 2018 https://doi.org/10.3892/ijo.2018.4322
Pages: 1391-1400
Copyright: © Matsuhashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Achieving tumor shrinkage may be a clinically relevant improvement in the treatment of metastatic colorectal cancer (mCRC). The present study attempted to evaluate early tumor shrinkage (ETS) and deepness of response over 6-8 courses of therapy, which were assessed previously in first-line trials of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies. A total of 37 patients with mCRC that was considered unresectable or borderline resectable were enrolled in the study. Patients exhibited the wild-type RAS gene, and anti-EGFR monoclonal antibodies were used as the first-line treatment in the Department of Surgical Oncology at Gifu University School of Medicine (Gifu, Japan) between January 2010 and March 2017. Tumor shrinkage and other characteristics were evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST) classifications (version 1.1). The 3-year overall survival (OS) rate was >60.0% for all cases (n=37). The mean tumor shrinkage rate in the right side of the colon according to the RECIST classifications was -11.1%, whereas that for CRC on the left side showed a statistically significant difference at -54.0% (P=0.042). In addition, the rates of OS for stable disease + progressive disease compared with partial response + complete response, and those of OS for conversion therapy compared with non-conversion therapy were significantly different (both P<0.001). Carcinoembryonic antigen (CEA) was suggested to be a possible predictive factor for convalescence due to the 50% drop in its value after the 6-8 courses of therapy. Overall, the predictive performance of ETS with respect to PFS and OS is at least as good as the standard RECIST response, with the advantage of an earlier assessment, and this may improve convalescence, with CEA as a marker in support of ETS over a clinical treatment course. In RAS wild-type patients, it is important to evaluate the rate of tumor shrinkage from the beginning of the first-line treatment until 6-8 courses of anti-EGFR monoclonal antibodies have been administered.

View Figures

View References

1	Fernandez FG, Drebin JA, Linehan DC, Dehdashti F, Siegel BA and Strasberg SM: Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET). Ann Surg. 240:438–450. 2004. View Article : Google Scholar : PubMed/NCBI
2	O'Neil BH and Goldberg RM: Innovations in chemotherapy for metastatic colorectal cancer: An update of recent clinical trials. Oncologist. 13:1074–1083. 2008. View Article : Google Scholar : PubMed/NCBI
3	Grothey A, Hedrick EE, Mass RD, Sarkar S, Suzuki S, Ramanathan RK, Hurwitz HI, Goldberg RM and Sargent DJ: Response-independent survival benefit in metastatic colorectal cancer: A comparative analysis of N9741 and AVF2107. J Clin Oncol. 26:183–189. 2008. View Article : Google Scholar : PubMed/NCBI
4	Tyagi P and Grothey A: Commentary on a phase III trial of bevacizumab plus XELOX or FOLFOX4 for first-line treatment of metastatic colorectal cancer: The NO16966 trial. Clin Colorectal Cancer. 6:261–264. 2006. View Article : Google Scholar
5	Arkenau HT, Arnold D, Cassidy J, Diaz-Rubio E, Douillard JY, Hochster H, Martoni A, Grothey A, Hinke A, Schmiegel W, et al: Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: A pooled analysis of randomized trials. J Clin Oncol. 26:5910–5917. 2008. View Article : Google Scholar : PubMed/NCBI
6	Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crinò L, Benedetti G, Evangelista W, Fanchini L, et al Gruppo Oncologico Nord Ovest: Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: The Gruppo Oncologico Nord Ovest. J Clin Oncol. 25:1670–1676. 2007. View Article : Google Scholar : PubMed/NCBI
7	Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, et al: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 360:1408–1417. 2009. View Article : Google Scholar : PubMed/NCBI
8	Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, et al: Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 27:663–671. 2009. View Article : Google Scholar
9	Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, et al: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study. J Clin Oncol. 26:2013–2019. 2008. View Article : Google Scholar : PubMed/NCBI
10	Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, Yu H, Oliner KS and Go WY: PEAK: A randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 32:2240–2247. 2014. View Article : Google Scholar : PubMed/NCBI
11	Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, et al: Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: A randomized clinical trial. JAMA. 317:2392–2401. 2017. View Article : Google Scholar : PubMed/NCBI
12	Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, et al: FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. Lancet Oncol. 15:1065–1075. 2014. View Article : Google Scholar : PubMed/NCBI
13	Stintzing S, Modest DP, Rossius L, Lerch MM, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, et al FIRE-3 investigators: FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): A post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol. 17:1426–1434. 2016. View Article : Google Scholar : PubMed/NCBI
14	Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ and Heinemann V: Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: Retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. Oct 10–2016.Epub ahead of print. PubMed/NCBI
15	Folprecht G, Gruenberger T, Bechstein WO, Raab HR, Lordick F, Hartmann JT, Lang H, Frilling A, Stoehlmacher J, Weitz J, et al: Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: The CELIM randomised phase 2 trial. Lancet Oncol. 11:38–47. 2010. View Article : Google Scholar
16	Van Loon K, Wigler D, Niedzwiecki D, Venook AP, Fuchs C, Blanke C, Saltz L, Goldberg RM and Meyerhardt JA: Comparison of dietary and lifestyle habits among stage III and metastatic colorectal cancer patients: Findings from CALGB 89803 and CALGB 80405. Clin Colorectal Cancer. 12:95–102. 2013. View Article : Google Scholar : PubMed/NCBI
17	Elez E, Argilés G and Tabernero J: First-line treatment of metastatic colorectal cancer: Interpreting FIRE-3, PEAK, and CALGB/SWOG 80405. Curr Treat Options Oncol. 16:522015. View Article : Google Scholar : PubMed/NCBI
18	Wanebo HJ, Rao B, Pinsky CM, Hoffman RG, Stearns M, Schwartz MK and Oettgen HF: Preoperative carcinoembryonic antigen level as a prognostic indicator in colorectal cancer. N Engl J Med. 299:448–451. 1978. View Article : Google Scholar : PubMed/NCBI
19	Moertel CG, O'Fallon JR, Go VL, O'Connell MJ and Thynne GS: The preoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of colorectal cancer. Cancer. 58:603–610. 1986. View Article : Google Scholar : PubMed/NCBI
20	Martin EW Jr, James KK, Hurtubise PE, Catalano P and Minton JP: The use of CEA as an early indicator for gastrointestinal tumor recurrence and second-look procedures. Cancer. 39:440–446. 1977. View Article : Google Scholar : PubMed/NCBI
21	Cooper MJ, Mackie CR, Skinner DB and Moossa AR: A reappraisal of the value of carcinoembryonic antigen in the management of patients with various neoplasms. Br J Surg. 66:120–123. 1979. View Article : Google Scholar : PubMed/NCBI
22	Steele G Jr, Ellenberg S, Ramming K, O'Connell M, Moertel C, Lessner H, Bruckner H, Horton J, Schein P, Zamcheck N, et al: CEA monitoring among patients in multi-institutional adjuvant G.I. therapy protocols. Ann Surg. 196:162–169. 1982. View Article : Google Scholar : PubMed/NCBI
23	Kuusela P, Jalanko H, Roberts P, Sipponen P, Mecklin JP, Pitkänen R and Mäkelä O: Comparison of CA19-9 and carcinoembryonic antigen (CEA) levels in the serum of patients with colorectal diseases. Br J Cancer. 49:135–139. 1984. View Article : Google Scholar : PubMed/NCBI
24	Filella X, Molina R, Grau JJ, Piqué JM, Garcia-Valdecasas JC, Astudillo E, Biete A, Bordas JM, Novell A, Campo E, et al: Prognostic value of CA 19.9 levels in colorectal cancer. Ann Surg. 216:55–59. 1992. View Article : Google Scholar : PubMed/NCBI
25	Kouri M, Pyrhönen S and Kuusela P: Elevated CA19-9 as the most significant prognostic factor in advanced colorectal carcinoma. J Surg Oncol. 49:78–85. 1992. View Article : Google Scholar : PubMed/NCBI
26	Nakayama T, Watanabe M, Teramoto T and Kitajima M: CA19-9 as a predictor of recurrence in patients with colorectal cancer. J Surg Oncol. 66:238–243. 1997. View Article : Google Scholar
27	Prager GW, Braemswig KH, Martel A, Unseld M, Heinze G, Brodowicz T, Scheithauer W, Kornek G and Zielinski CC: Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer. Cancer Sci. 105:996–1001. 2014. View Article : Google Scholar : PubMed/NCBI
28	Bramswig KH, Poettler M, Unseld M, Wrba F, Uhrin P, Zimmermann W, Zielinski CC and Prager GW: Soluble carcinoembryonic antigen activates endothelial cells and tumor angiogenesis. Cancer Res. 73:6584–6596. 2013. View Article : Google Scholar : PubMed/NCBI
29	Carmeliet P: Angiogenesis in life, disease and medicine. Nature. 438:932–936. 2005. View Article : Google Scholar : PubMed/NCBI
30	Ocvirk J, Brodowicz T, Wrba F, Ciuleanu TE, Kurteva G, Beslija S, Koza I, Pápai Z, Messinger D, Yilmaz U, et al: Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial. World J Gastroenterol. 16:3133–3143. 2010. View Article : Google Scholar : PubMed/NCBI
31	Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, et al: ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 27:1386–1422. 2016. View Article : Google Scholar : PubMed/NCBI
32	Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, Mezi S, Tomasello G, Ronzoni M, Zaniboni A, et al: FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: Updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 16:1306–1315. 2015. View Article : Google Scholar : PubMed/NCBI
33	Sasaki Y, Osada S, Mori R, Imai H, Tanaka Y, Matsuhashi N, Okumura N, Nonaka K, Takahashi T and Yoshida K: Determining timing of hepatectomy for colorectal cancer with distant metastasis according to imaging-based tumor shrinkage ratio. Int J Med Sci. 10:1231–1241. 2013. View Article : Google Scholar : PubMed/NCBI
34	Sasaki Y, Osada S, Matsui S, Imai H, Tanahashi T, Tanaka Y, Matsuhashi N, Okumura N, Yamaguchi K and Yoshida K: Preoperative chemotherapy can change the surgical procedure for hepatectomy in patients with liver metastasis of colorectal cancer. Anticancer Res. 35:5485–5489. 2015.PubMed/NCBI
35	Benson AB III, Venook AP, Cederquist L, Chan E, Chen YJ, Cooper HS, Deming D, Engstrom PF, Enzinger PC, Fichera A, et al: Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 15:370–398. 2017. View Article : Google Scholar : PubMed/NCBI