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Article

Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer

  • Authors:
    • Hiroshi Osawa
  • View Affiliations / Copyright

    Affiliations: Department of Oncology and Hematology, Edogawa Hospital, Tokyo 133‑0052, Japan
  • Pages: 365-372
    |
    Published online on: January 31, 2017
       https://doi.org/10.3892/mco.2017.1145
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Abstract

Regorafenib (Reg) is an oral multikinase inhibitor that has achieved improved overall survival in patients with metastatic colorectal cancer (mCRC) in the salvage therapy setting. However, Reg is difficult to manage and determine the optimal dose due to adverse events (AEs). The objective of this study was to retrospectively evaluate the clinical benefit and determine the optimal dose of Reg in mCRC patients. A total of 20 mCRC patients were enrolled in this retrospective study. Initially, 8 patients who received a starting dose of 160 mg Reg (160 mg group) once a day were evaluated; however, they were unable to continue with the initial dose of 160 mg due to grade 3 adverse events (AEs), such as hand‑foot skin reaction (HFSR) and small intestinal hemorrhage. Furthermore, 2 of the 8 patients refused subsequent treatment due to HFSR and the remaining 6 patients received a dose reduction from 160 to 120 mg Reg. A reduced dose of 120 mg Reg was also assessed with our dose modification method in 12 patients (120 mg group). The optimal response of the 160 and 120 mg group patients was 0.0 and 8.3% (1/12), respectively. In the 160 mg group, 3 patients exhibited stable disease (SD). Surprisingly, among the the 120 mg group patients 1 exhibited partial response (PR) and 6 had SD. The PR case displayed shrinkage of the local recurrence and morphological changes. One of the SD cases exhibited formation of a cavity in the lung metastasis, with intralesional morphological changes of the liver metastasis. The duration of the treatment in the PR case and the SD case with the cavitation was 6.5 months (9 cycles) and 5 months (6 cycles), respectively. The median progression­‑free survival (PFS) was 77 days (range, 30‑230+ days) and the median overall survival (OS) was 204 days (range, 53‑511+ days). The final date of the follow‑up period was July 31, 2016. The 160 mg group was associated with a 25% (3/8) incidence of HFSR, 12.5% (1/8) of small intestinal hemorrhage and 12.5% (1/8) of anemia and thrombocytopenia; the AEs were grade >3. The 120 mg group was associated with an incidence of only 8.3% (1/12) of grade >3 hypertension. Thus, the 120 mg group experienced lower treatment‑related toxicity compared with the 160 mg group. Despite a reduced initial dose of Reg, a significant effect was observed, with 1 PR and 6 favorable SD cases, with good tolerability. Therefore, an initial dose modification of 120 mg Reg is recommended as an alternative strategy for the treatment of mCRC in the salvage setting.
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1 

Matsuda A, Matsuda T, Shibata A, Katanoda K, Sobue T and Nishimoto H and Nishimoto H: Japan Cancer Surveillance Research Grou: Cancer incidence and incidence rates in Japan in 2008: A study of 25 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol. 44:388–396. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Haggar FA and Boushey RP: Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 22:191–197. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Arnold D and Stein A: New developments in the second-line treatment of metastatic colorectal cancer: Potential place in therapy. Drugs. 73:883–891. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Van Cutsem E, Cervantes A, Nordlinger B and Arnold D: ESMO Guidelines Working Group: Metastatic colorectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 25:(Suppl 3). iii1–iii9. 2014. View Article : Google Scholar : PubMed/NCBI

5 

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

6 

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

7 

Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M and Koralewski P: Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: The OPUS study. Ann Oncol. 22:1535–1546. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejper S, et al: Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: Updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 29:2011–2019. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, et al: Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 369:1023–1034. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Modest DP, Stintzing S, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmuller C, Kahl C, et al: Impact of subsequent therapies on outcome of the FIRE-3/AIO KRK0306 trial: First-line therapy with FOLFIRI plus cetuximab or bevacizumab in patients with KRAS wild-type tumors in metastatic colorectal cancer. J Clin Oncol. 33:3718–3726. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Mahoney MR, O'Neil BH, Shaw JM, Polite BN, Hochster HS, Atkins JN, et al: CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). J Clin Oncol. 32:(Suppl; abstr LBA3). 5s2014.

12 

Yamazaki K, Nagase M, Tamagawa H, Ueda S, Murata K Tamura, Tsuda T, Baba E, Tsuda M, Moriwaki T, Esaki T, et al: A randomized phase III trial of mFOLFOX6 plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment for metastatic colorectal cancer: West Japan Oncology Group study 4407G (WJOG4407G). J Clin Oncol. 32:(Suppl; abstr 3534). 5s2014.

13 

Schmieder R, Hoffmann J, Becker M, Bhargava A, Müller T, Kahmann N, Ellinghaus P, Adams R, Rosenthal A, Thierauch KH, et al: Regorafenib (BAY 73–4506): Antitumor and antimetastatic activities in preclinical models of colorectal cancer. Int J Cancer. 15:1487–1496. 2014. View Article : Google Scholar

14 

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, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 381:303–312. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Yoshino T, Komatsu Y, Yamada Y, Yamazaki K, Tsuji A, Ura T, Grothey A, Van Cutsem E, Wagner A, Cihon F, et al: Randomized phase III trial of regorafenib in metastatic colorectal cancer: Analysis of the CORRECT Japanese and non-Japanese subpopulations. Invest New Drugs. 33:740–750. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, Xu J, Bai Y, Chi Y, Wang L, et al: Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 16:619–629. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Grothey A, Sobrero AF, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, et al: Time profile of adverse events (AEs) from regorafenib (REG) treatment for metastatic colorectal cancer (mCRC) in the phase III CORRECT study. J Clin Oncol. 31:(Suppl; abstr 3637). 2013.

18 

McLellan B, Ciardiello F, Lacouture ME, Segaert S and Van Cutsem E: Regorafenib-associated hand-foot skin reaction: Practical advice on diagnosis, prevention, and management. Ann Oncol. 26:2017–2026. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Mross K, Frost A, Steinbild S, Hedbom S, Büchert M, Fasol U, Unger C, Krätzschmar J, Heinig R, Boix O, et al: A phase I dose-escalation study of regorafenib (BAY 73–4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 18:2658–2667. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Ricotta R, Sartore-Bianchi A, Verrioli A, Vanzulli A and Siena S: Regorafenib for metastatic colorectal cancer. Lancet. 381:15372013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Osawa H: Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer. Mol Clin Oncol 6: 365-372, 2017.
APA
Osawa, H. (2017). Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer. Molecular and Clinical Oncology, 6, 365-372. https://doi.org/10.3892/mco.2017.1145
MLA
Osawa, H."Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer". Molecular and Clinical Oncology 6.3 (2017): 365-372.
Chicago
Osawa, H."Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer". Molecular and Clinical Oncology 6, no. 3 (2017): 365-372. https://doi.org/10.3892/mco.2017.1145
Copy and paste a formatted citation
x
Spandidos Publications style
Osawa H: Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer. Mol Clin Oncol 6: 365-372, 2017.
APA
Osawa, H. (2017). Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer. Molecular and Clinical Oncology, 6, 365-372. https://doi.org/10.3892/mco.2017.1145
MLA
Osawa, H."Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer". Molecular and Clinical Oncology 6.3 (2017): 365-372.
Chicago
Osawa, H."Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer". Molecular and Clinical Oncology 6, no. 3 (2017): 365-372. https://doi.org/10.3892/mco.2017.1145
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