Skip to main content
Top
Published in: Clinical and Translational Oncology 11/2014

Open Access 01-11-2014 | Educational series – Red Series

Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer

Authors: J. Sastre, G. Argilés, M. Benavides, J. Feliú, P. García-Alfonso, R. García-Carbonero, C. Grávalos, C. Guillén-Ponce, M. Martínez-Villacampa, C. Pericay

Published in: Clinical and Translational Oncology | Issue 11/2014

Login to get access

Abstract

Colorectal cancer is one of the most common tumors worldwide and at least 50 % of patients with this disease develop metastases. In this setting, additional treatment options are needed for patients presenting disease progression after exhausting all standard therapies. Regorafenib is an orally administered multikinase inhibitor which has been shown to provide survival benefits to patients with metastatic colorectal cancer (mCRC). Although most adverse events (AEs) associated with regorafenib may resolve within the first 8 weeks of treatment, some of them may require dose reduction or treatment interruption. Overall, while remaining aware of the safety profile of regorafenib and how to manage the most common toxicities related to its use, this drug should be considered a new standard of care for patients with pretreated mCRC. This review addresses practical aspects of its use, such as dosing, patient monitoring, and management of the most common regorafenib-related AEs.
Literature
1.
go back to reference National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN guidelines®): colon cancer, version 3. 2014. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN guidelines®): colon cancer, version 3. 2014.
2.
go back to reference Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol. 2012;23:2479–516.PubMedCrossRef Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol. 2012;23:2479–516.PubMedCrossRef
4.
go back to reference Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schutz G, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011;129:245–55.PubMedCrossRef Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schutz G, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011;129:245–55.PubMedCrossRef
5.
go back to reference Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, 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. 2012;18:2658–67.PubMedCrossRef Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, 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. 2012;18:2658–67.PubMedCrossRef
6.
go back to reference Strumberg D, Scheulen ME, Schultheis B, Richly H, Frost A, Buchert M, et al. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. Br J Cancer. 2012;106:1722–7.PubMedCrossRefPubMedCentral Strumberg D, Scheulen ME, Schultheis B, Richly H, Frost A, Buchert M, et al. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. Br J Cancer. 2012;106:1722–7.PubMedCrossRefPubMedCentral
7.
go back to reference Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–12.PubMedCrossRef Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–12.PubMedCrossRef
8.
go back to reference Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:295–302.PubMedCrossRef Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:295–302.PubMedCrossRef
9.
go back to reference Grothey A, Sobrero AF, Siena S, Falcone A, Ychou M, Humblet Y, et al. Time profile of adverse events (AEs) from regorafenib (REG) treatment for metastatic colorectal cancer (mCRC) in the phase III CORRECT study. ASCO Meet Abstr. 2013;31:3637. Grothey A, Sobrero AF, Siena S, Falcone A, Ychou M, Humblet Y, et al. Time profile of adverse events (AEs) from regorafenib (REG) treatment for metastatic colorectal cancer (mCRC) in the phase III CORRECT study. ASCO Meet Abstr. 2013;31:3637.
10.
go back to reference Siena S, Grothey A, Sobrero A, Falcone A, Ychou M, Lenz HJ et al. Effects of regorafenib therapy on health-related quality of life in patients with metastatic colorectal cancer in the phase III CORRECT study. Amsterdam: European Cancer Congress ECCO; abstract 2156;2013. Siena S, Grothey A, Sobrero A, Falcone A, Ychou M, Lenz HJ et al. Effects of regorafenib therapy on health-related quality of life in patients with metastatic colorectal cancer in the phase III CORRECT study. Amsterdam: European Cancer Congress ECCO; abstract 2156;2013.
11.
go back to reference Grothey A, Van Cutsem E, Sobrero AF, Siena S, Falcone A, Ychou M, et al. Time course of regorafenib-associated adverse events in the phase III CORRECT study. ASCO Meet Abstr. 2013;31:467. Grothey A, Van Cutsem E, Sobrero AF, Siena S, Falcone A, Ychou M, et al. Time course of regorafenib-associated adverse events in the phase III CORRECT study. ASCO Meet Abstr. 2013;31:467.
12.
go back to reference Yennurajalingam S, Frisbee-Hume S, Palmer JL, Delgado-Guay MO, Bull J, Phan AT, et al. Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J Clin Oncol. 2013;31:3076–82.PubMedCrossRef Yennurajalingam S, Frisbee-Hume S, Palmer JL, Delgado-Guay MO, Bull J, Phan AT, et al. Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J Clin Oncol. 2013;31:3076–82.PubMedCrossRef
13.
go back to reference Tassinari D, Flamini E, Poggi B, Fochessati F, Fantini M, Fabbri L, et al. Clinical benefit of palliative treatment of cancer cachexia with medroxyprogesterone acetate (MPA). ASCO Meet Abstr. 2004;22:8213. Tassinari D, Flamini E, Poggi B, Fochessati F, Fantini M, Fabbri L, et al. Clinical benefit of palliative treatment of cancer cachexia with medroxyprogesterone acetate (MPA). ASCO Meet Abstr. 2004;22:8213.
14.
go back to reference Campos MP, Hassan BJ, Riechelmann R, Del Giglio A. Cancer-related fatigue: a practical review. Ann Oncol. 2011;22:1273–9.PubMedCrossRef Campos MP, Hassan BJ, Riechelmann R, Del Giglio A. Cancer-related fatigue: a practical review. Ann Oncol. 2011;22:1273–9.PubMedCrossRef
15.
go back to reference Grothey A, George S, van Cutsem E, Blay JY, Sobrero A, Demetri GD. Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. Oncologist. 2014;19:669–80.PubMedCrossRef Grothey A, George S, van Cutsem E, Blay JY, Sobrero A, Demetri GD. Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. Oncologist. 2014;19:669–80.PubMedCrossRef
16.
go back to reference Bayer HealthCare Pharmaceuticals Inc. Clinical study report 14387 (CORRECT). Wayne: Bayer HealthCare Pharmaceuticals Inc; 2012, pp. 1–179. Bayer HealthCare Pharmaceuticals Inc. Clinical study report 14387 (CORRECT). Wayne: Bayer HealthCare Pharmaceuticals Inc; 2012, pp. 1–179.
17.
go back to reference Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.PubMedCrossRef Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.PubMedCrossRef
18.
go back to reference Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369:1023–34.PubMedCrossRef Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369:1023–34.PubMedCrossRef
19.
go back to reference Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu 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. 2011;29:2011–9.PubMedCrossRef Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu 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. 2011;29:2011–9.PubMedCrossRef
20.
go back to reference Eisen T, Sternberg CN, Robert C, Mulders P, Pyle L, Zbinden S, et al. Targeted therapies for renal cell carcinoma: review of adverse event management strategies. J Natl Cancer Inst. 2012;104:93–113.PubMedCrossRef Eisen T, Sternberg CN, Robert C, Mulders P, Pyle L, Zbinden S, et al. Targeted therapies for renal cell carcinoma: review of adverse event management strategies. J Natl Cancer Inst. 2012;104:93–113.PubMedCrossRef
21.
go back to reference Qi WX, He AN, Shen Z, Yao Y. Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta-analysis. Br J Clin Pharmacol. 2013;76:348–57.PubMedCrossRefPubMedCentral Qi WX, He AN, Shen Z, Yao Y. Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta-analysis. Br J Clin Pharmacol. 2013;76:348–57.PubMedCrossRefPubMedCentral
22.
go back to reference Qi WX, Lin F, Sun YJ, Tang LN, He AN, Yao Y, et al. Incidence and risk of hypertension with pazopanib in patients with cancer: a meta-analysis. Cancer Chemother Pharmacol. 2013;71:431–9.PubMedCrossRef Qi WX, Lin F, Sun YJ, Tang LN, He AN, Yao Y, et al. Incidence and risk of hypertension with pazopanib in patients with cancer: a meta-analysis. Cancer Chemother Pharmacol. 2013;71:431–9.PubMedCrossRef
23.
go back to reference Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol. 2009;48:9–17.PubMedCrossRef Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol. 2009;48:9–17.PubMedCrossRef
24.
go back to reference Bensinger W, Schubert M, Ang KK, Brizel D, Brown E, Eilers JG, et al. NCCN Task Force Report. Prevention and management of mucositis in cancer care. J Natl Compr Cancer Netw. 2008;6(Suppl 1):S1–21 (quiz S22–24). Bensinger W, Schubert M, Ang KK, Brizel D, Brown E, Eilers JG, et al. NCCN Task Force Report. Prevention and management of mucositis in cancer care. J Natl Compr Cancer Netw. 2008;6(Suppl 1):S1–21 (quiz S22–24).
25.
go back to reference Clarkson JE, Worthington HV, Furness S, McCabe M, Khalid T, Meyer S. Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2010;CD001973. Clarkson JE, Worthington HV, Furness S, McCabe M, Khalid T, Meyer S. Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2010;CD001973.
26.
go back to reference Harris DJ, Eilers J, Harriman A, Cashavelly BJ, Maxwell C. Putting evidence into practice: evidence-based interventions for the management of oral mucositis. Clin J Oncol Nurs. 2008;12:141–52.PubMedCrossRef Harris DJ, Eilers J, Harriman A, Cashavelly BJ, Maxwell C. Putting evidence into practice: evidence-based interventions for the management of oral mucositis. Clin J Oncol Nurs. 2008;12:141–52.PubMedCrossRef
27.
go back to reference Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27:127–45.PubMedCrossRef Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27:127–45.PubMedCrossRef
28.
go back to reference Lalla RV, Ashbury FD. The MASCC/ISOO mucositis guidelines: dissemination and clinical impact. Support Care Cancer. 2013;21:3161–3.PubMedCrossRef Lalla RV, Ashbury FD. The MASCC/ISOO mucositis guidelines: dissemination and clinical impact. Support Care Cancer. 2013;21:3161–3.PubMedCrossRef
29.
go back to reference Peterson DE, Bensadoun RJ, Roila F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22(Suppl 6):vi78–84. Peterson DE, Bensadoun RJ, Roila F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22(Suppl 6):vi78–84.
30.
go back to reference Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2011;CD000978. Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2011;CD000978.
32.
go back to reference Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008;13:1001–11.PubMedCrossRef Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008;13:1001–11.PubMedCrossRef
34.
go back to reference Supplement to: Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381:303–312. Supplement to: Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381:303–312.
Metadata
Title
Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer
Authors
J. Sastre
G. Argilés
M. Benavides
J. Feliú
P. García-Alfonso
R. García-Carbonero
C. Grávalos
C. Guillén-Ponce
M. Martínez-Villacampa
C. Pericay
Publication date
01-11-2014
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 11/2014
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-014-1212-8

Other articles of this Issue 11/2014

Clinical and Translational Oncology 11/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine