Combination chemotherapy with TAS‑102 plus bevacizumab in salvage‑line treatment of metastatic colorectal cancer: A single‑center, retrospective study examining the prognostic value of the modified Glasgow Prognostic Score in salvage‑line therapy of metastatic colorectal cancer

Matsuhashi,Nobuhisa; Takahashi,Takao; Fujii,Hironori; Suetsugu,Tomonari; Fukada,Masahiro; Iwata,Yoshinori; Tokumaru,Yoshihisa; Imai,Takeharu; Mori,Ryutaro; Tanahashi,Toshiyuki; Matsui,Satoshi; Imai,Hisashi; Tanaka,Yoshihiro; Yamaguch,Kazuya; Futamura,Manabu; Yoshida,Kazuhiro

doi:10.3892/mco.2019.1899

Combination chemotherapy with TAS‑102 plus bevacizumab in salvage‑line treatment of metastatic colorectal cancer: A single‑center, retrospective study examining the prognostic value of the modified Glasgow Prognostic Score in salvage‑line therapy of metastatic colorectal cancer

Authors:
- Nobuhisa Matsuhashi
- Takao Takahashi
- Hironori Fujii
- Tomonari Suetsugu
- Masahiro Fukada
- Yoshinori Iwata
- Yoshihisa Tokumaru
- Takeharu Imai
- Ryutaro Mori
- Toshiyuki Tanahashi
- Satoshi Matsui
- Hisashi Imai
- Yoshihiro Tanaka
- Kazuya Yamaguch
- Manabu Futamura
- Kazuhiro Yoshida
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Affiliations: Department of Surgical Oncology, Gifu University School of Medicine, Gifu 501‑1194, Japan, Department of Pharmacy, Gifu University Hospital, Gifu 501‑1194, Japan
Published online on: July 18, 2019 https://doi.org/10.3892/mco.2019.1899
Pages: 390-396

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Abstract

The combination regimen of TAS‑102, a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, with bevacizumab (C‑TASK FORCE), a selective monoclonal antibody inhibitor of vascular endothelial growth factor‑A, as salvage‑line therapy for metastatic colorectal cancer (mCRC) was established based on its high clinical effectiveness. The aim of the present study was to evaluate the prognostic accuracy of the modified Glasgow Prognostic Score (mGPS) in patients receiving TAS‑102 plus bevacizumab. The study included 17 patients (12 men and 5 women, mean age 60.4±13.4 years) with unresectable mCRC who were confirmed to have wild‑type or mutant RAS genes. The patients received salvage‑line treatment with TAS‑102 plus bevacizumab at the Surgical Oncology Department of Gifu University School of Medicine between March 2016 and August 2018. The study population was heavily pretreated; the majority of the patients (71%) had received ≥4 prior regimens and, in addition to fluoropyrimidine, irinotecan and oxaliplatin, all had received bevacizumab (100%) and either cetuximab or panitumumab (47%). The RAS status was wild‑type in 9 (53%) and mutant in 8 (47%) patients. The primary tumor locations included the right‑sided colon in 5 patients (29%; cecum in 2 and transverse colon in 3 cases) and left‑sided colorectum in 12 patients [71%; sigmoid colon in 4, rectosigmoid (Rs) in 4, and rectum above/below the peritoneal reflection (Ra/b) in 4 cases]. Metastatic sites included the liver in 15 (88%), lung in 13 (76%), lymph nodes in 7 (41%), and peritoneal dissemination in 5 (24%) patients. The number of metastatic sites was 1 in 3 (18%) and >2 in 14 (82%) patients. Their first staging imaging scans (after 2 cycles of therapy) were available for review in all 17 patients. At first evaluation, 5 (29%) patients had progressive disease (PD), 12 (71%) had stable disease, and none had a partial response to TAS‑102 plus bevacizumab. The median overall survival (OS) of 14.1 months and progression‑free survival (PFS) of 6.8 months were comparable to the 11.2 and 5.6 months, respectively, in the C‑TASK FORCE study. Upon considering three groups, namely mGPS 0, mGPS 1 and mGPS 2, the median PFS times were signiﬁcantly different (mGPS 0 vs. mGPS 2, P=0.02; and mGPS 1 vs. mGPS 2, P=0.06). The median PFS times in the mGPS 0, 1 and 2 groups were 12.1, 4.8 and 2.3 months, respectively. Median OS was also signiﬁcantly different (mGPS 0 vs. mGPS 2, P=0.01; and mGPS 1 vs. mGPS 2, P=0.04). The median OS times in the mGPS 0, 1 and 2 groups were 14.0, not reached, and 2 months, respectively. The present study demonstrated the efficacy and safety of the TAS‑102 plus bevacizumab combination as salvage‑line treatment. This combination therapy (the TAS‑102 plus bevacizumab) has obtained valid results with PFS OS as well as C‑TASK.FORCE study. The results of the present study also conﬁrmed the prognostic accuracy of mGPS in salvage‑line treatment of patients with mCRC.

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1	Center MM, Jemal A and Ward E: International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 18:1688–1694. 2009. View Article : Google Scholar : PubMed/NCBI
2	Cheng AL, Li J, Vaid AK, Ma BB, The C, Ahn JB, Bello M, Charoentum C, Chen LT, de Lima Lopes G Jr, et al: Adaptation of international guidelines for metastatic colorectal cancer: An Asian consensus. Clin Colorectal Cancer. 13:145–155. 2014. View Article : Google Scholar : PubMed/NCBI
3	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancersin 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
4	Lemmens V, van Steenbergen L, Janssen-Heijnen M, Martijn H, Rutten H and Coebergh JW: Trends in colorectal cancer in the south of the Netherlands 1975–2007: rectal cancer survival levels with colon cancer survival. Acta Oncol. 49:784–796. 2010. View Article : Google Scholar : PubMed/NCBI
5	Van Cutsem E, Borràs JM, Castells A, Ciardiello F, Ducreux M, Haq A, Schmoll HJ and Tabernero J: Improving outcomes in colorectal cancer: where do we go from here? Eur J Cancer. 49:2476–2485. 2013. View Article : Google Scholar : PubMed/NCBI
6	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
7	Yamada Y, Denda T, Gamoh M, Iwanaga I, Yuki S, Shimodaira H, Nakamura M, Yamaguchi T, Ohori H, Kobayashi K, et al: S-1 and irinotecan plus bevacizumab vs. mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): A randomized, open-label, phase III, noninferiority trial. Ann Oncol. 29:624–631. 2018. View Article : Google Scholar : PubMed/NCBI
8	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
9	Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, Yamazaki K, Shimada Y, Tabernero J, Komatsu Y, et al: RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J. 372:1909–1919. 2015. View Article : Google Scholar
10	Melnyk O, Zimmerman M, Kim KJ and Shuman M: Neutralizing anti-vascular endothelial growth factor antibody inhibits further growth of established prostate cancer and metastases in a pre-clinical model. J Urol. 161:960–963. 1999. View Article : Google Scholar : PubMed/NCBI
11	Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, Bohlen P and Kerbel RS: Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest. 105:R15–R24. 2000. View Article : Google Scholar : PubMed/NCBI
12	Kuboki Y, Nishina T, Shinozaki E, Yamazaki K, Shitara K, Okamoto W, Kajiwara T, Matsumoto T, Tsushima T, Mochizuki N, et al: TAS-102 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE): An investigator-initiated, open-label, single-arm, multicentre, phase 1/2 study. Lancet Oncol. 18:1172–1181. 2017. View Article : Google Scholar : PubMed/NCBI
13	Yoshino T, Oki E, Nozawa H, Eguchi-Nakajima T, Taniguchi H, Morita S, Takenaka N, Ozawa D and Shirao K: Rationale and design of the TRUSTY study: A randomised, multicentre, open-label phase II/III study of trifluridine/tipiracil plus bevacizumab versus irinotecan, fluoropyrimidine plus bevacizumab as second-line treatment in patients with metastatic colorectal cancer progressive during or following first-line oxaliplatin-based chemotherapy. ESMO Open. 3:e0004112018. View Article : Google Scholar : PubMed/NCBI
14	Douglas E and McMillan DC: Towards a simple objective framework for the investigation and treatment of cancer cachexia: The glasgow prognostic score. Cancer Treat Rev. 40:685–691. 2014. View Article : Google Scholar : PubMed/NCBI
15	Takeno S, Hashimoto T, Shibata R, Maki K, Shiwaku H, Yamana I, Yamashita R and Yamashita Y: The high-sensitivity modified Glasgow prognostic score is superior to the modified Glasgow prognostic score as a prognostic predictor in patients with resectable gastric cancer. Oncology. 87:205–214. 2014. View Article : Google Scholar : PubMed/NCBI
16	Common Terminology Criteria for Adverse Events (CTCAE) Version5.0 Published Nov 27, 2017.
17	Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, et al: Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: A multicentre randomised trial. Lancet. 355:1041–1047. 2000. View Article : Google Scholar : PubMed/NCBI
18	Tournigand C, André T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, et al: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol. 22:229–237. 2004. View Article : Google Scholar : PubMed/NCBI
19	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
20	Grothey A, Sargent D, Goldberg RM and Schmoll HJ: Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 22:1209–1214. 2004. View Article : Google Scholar : PubMed/NCBI
21	Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 350:2335–2342. 2004. View Article : Google Scholar : PubMed/NCBI
22	Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, et al: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicenter, randomised, placebo-controlled phase 3 trial. Lancet. 381:303–312. 2013. View Article : Google Scholar : PubMed/NCBI
23	Tsukihara H, Nakagawa F, Sakamoto K, Ishida K, Tanaka N, Okabe H, Uchida J, Matsuo K and Takechi T: Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, together with bevacizumab, cetuximab, or panitumumab on human colorectal cancer xenografts. Oncol Rep. 33:2135–2142. 2015.PubMed/NCBI
24	Jain RK: Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat Med. 7:987–989. 2001. View Article : Google Scholar : PubMed/NCBI
25	Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausová J, Macarulla T, Ruff P, van Hazel GA, Moiseyenko V, Ferry D, et al: Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 30:3499–3506. 2012. View Article : Google Scholar : PubMed/NCBI
26	Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, Ciuleanu TE, Portnoy DC, Van Cutsem E, Grothey A, et al: Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): A randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 16:499–508. 2015. View Article : Google Scholar : PubMed/NCBI
26	Kasi PM, Kotani D, Cecchini M, Shitara K, Ohtsu A, Ramanathan RK, Hochster HS, Grothey A and Yoshino T: Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: A cohort study. BMC Cancer. 16:4672016. View Article : Google Scholar : PubMed/NCBI
27	McMillan DC: An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer. Proc Nutr Soc. 67:257–262. 2008. View Article : Google Scholar : PubMed/NCBI
28	Deans DA, Tan BH, Wigmore SJ, Ross JA, de Beaux AC, Paterson-Brown S and Fearon KC: The influence of systemic inflammation, dietary intake and stage of disease on rate of weight loss in patients with gastro-oesophageal cancer. Br J Cancer. 100:63–69. 2009. View Article : Google Scholar : PubMed/NCBI
29	Morley JE, Thomas DR and Wilson MM: Cachexia: Pathophysiology and clinical relevance. Am J Clin Nutr. 83:735–743. 2006. View Article : Google Scholar : PubMed/NCBI
30	Ishizuka M, Nagata H, Takagi K, Horie T and Kubota K: Inflammation-based prognostic score is a novel predictor of postoperative outcome in patients with colorectal cancer. Ann Surg. 246:1047–1051. 2007. View Article : Google Scholar : PubMed/NCBI
31	Proctor MJ, Morrison DS, Talwar D, Balmer SM, O'Reilly DS, Foulis AK, Horgan PG and McMillan DC: An inflammation- based prognostic score (mGPS) predicts cancer survival independent of tumour site: A glasgow inflammation outcome study. Br J Cancer. 104:726–732. 2011. View Article : Google Scholar : PubMed/NCBI
32	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