Skip to main content
Erschienen in: Advances in Therapy 8/2019

17.06.2019 | Original Research

Meta-Analysis of Regorafenib-Associated Adverse Events and Their Management in Colorectal and Gastrointestinal Stromal Cancers

verfasst von: Ganfeng Xie, Yuzhu Gong, Shuang Wu, Chong Li, Songtao Yu, Zhe Wang, Jianfang Chen, Quanfeng Zhao, Jianjun Li, Houjie Liang

Erschienen in: Advances in Therapy | Ausgabe 8/2019

Einloggen, um Zugang zu erhalten

Abstract

Introduction

To assess the risk factors associated with regorafenib-related adverse events (AEs) in metastatic colorectal cancer (mCRC) and gastrointestinal stromal tumors (GIST). We also evaluated different measures of combatting AEs and their success rate to aid physicians in early identification and management of reported AEs.

Methods

A literature search was conducted through the electronic databases PubMed, Embase, and Cochrane Central Register of Controlled Trials up to May 2018 according to the pre-specified inclusion and exclusion criteria. Pooled estimates with Pearson correlation were obtained with fixed or random-effects models.

Results

From our analysis, it was evident that AEs were more common in patients aged less than 65 years compared to those aged at least 65 years (71.3% vs. 27.6%, p = 0.001). A statistically significant correlation was observed between the occurrence of AEs and a dose of 160 mg (r = 0.967; p = 0.001) while no significant correlation was found at 120 mg and 80 mg. The common measures used to manage AEs included lowering the regorafenib dose (41%), intermittent drug withdrawal (66.7%), and complete drug withdrawal (19%). About 57% of patients recovered from AE after their initiating dose was lowered.

Conclusion

Regorafenib-associated AEs are more common at an initiating dose of 160 mg. Considering that the efficacy depends on the dosage, 120 mg might be a better choice for mCRC and GIST patients; further studies are needed to validate the results of our analysis. Further prompt identification and management of AEs are required to help the patients continue with drug therapy.
Literatur
1.
Zurück zum Zitat Zhang Z, Jiang T, Wang W, Piao D. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumor after failure with imatinib and sunitinib treatment: a meta-analysis. Medicine. 2017;96:e8698.CrossRefPubMedPubMedCentral Zhang Z, Jiang T, Wang W, Piao D. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumor after failure with imatinib and sunitinib treatment: a meta-analysis. Medicine. 2017;96:e8698.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Giampieri R, Prete M del, Prochilo T, et al. Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: the TRIBUTE analysis. Scientific Reports [Internet]. 2017;7. http://www.nature.com/articles/srep45703. Accessed 11 July 2018. Giampieri R, Prete M del, Prochilo T, et al. Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: the TRIBUTE analysis. Scientific Reports [Internet]. 2017;7. http://​www.​nature.​com/​articles/​srep45703. Accessed 11 July 2018.
3.
Zurück zum Zitat Crona DJ, Keisler MD, Walko CM. Regorafenib: a novel multitargeted tyrosine kinase inhibitor for colorectal cancer and gastrointestinal stromal tumors. Ann Pharmacother. 2013;47:1685–96.CrossRefPubMed Crona DJ, Keisler MD, Walko CM. Regorafenib: a novel multitargeted tyrosine kinase inhibitor for colorectal cancer and gastrointestinal stromal tumors. Ann Pharmacother. 2013;47:1685–96.CrossRefPubMed
4.
5.
Zurück zum Zitat Cao M, Li F, Wang Y, Zhang J. Treatment-related serious adverse events and fatal adverse events with regorafenib in cancer patients: a meta-analysis of phase 3 randomized controlled trials. Investig New Drugs. 2017;35:834–8.CrossRef Cao M, Li F, Wang Y, Zhang J. Treatment-related serious adverse events and fatal adverse events with regorafenib in cancer patients: a meta-analysis of phase 3 randomized controlled trials. Investig New Drugs. 2017;35:834–8.CrossRef
6.
Zurück zum Zitat Wilhelm SM, Dumas J, Adnane L, 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.CrossRefPubMed Wilhelm SM, Dumas J, Adnane L, 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.CrossRefPubMed
7.
Zurück zum Zitat Strumberg D, Schultheis B. Regorafenib for cancer. Expert Opin Investig Drugs. 2012;21:879–89.CrossRefPubMed Strumberg D, Schultheis B. Regorafenib for cancer. Expert Opin Investig Drugs. 2012;21:879–89.CrossRefPubMed
8.
Zurück zum Zitat Grothey A, Cutsem EV, Sobrero A, 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.CrossRefPubMed Grothey A, Cutsem EV, Sobrero A, 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.CrossRefPubMed
9.
Zurück zum Zitat Demetri GD, Reichardt P, Kang Y-K, 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.CrossRefPubMed Demetri GD, Reichardt P, Kang Y-K, 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.CrossRefPubMed
10.
Zurück zum Zitat De Wit M, Boers-Doets CB, Saettini A, et al. Prevention and management of adverse events related to regorafenib. Support Care Cancer. 2014;22:837–46.CrossRefPubMed De Wit M, Boers-Doets CB, Saettini A, et al. Prevention and management of adverse events related to regorafenib. Support Care Cancer. 2014;22:837–46.CrossRefPubMed
11.
Zurück zum Zitat Krishnamoorthy SK, Relias V, Sebastian S, Jayaraman V, Saif MW. Management of regorafenib-related toxicities: a review. Ther Adv Gastroenterol. 2015;8:285–97.CrossRef Krishnamoorthy SK, Relias V, Sebastian S, Jayaraman V, Saif MW. Management of regorafenib-related toxicities: a review. Ther Adv Gastroenterol. 2015;8:285–97.CrossRef
12.
Zurück zum Zitat Wood LS, Lemont H, Jatoi A, et al. Practical considerations in the management of hand-foot skin reaction caused by multikinase inhibitors. Commun Oncol. 2010;7:23–9.CrossRef Wood LS, Lemont H, Jatoi A, et al. Practical considerations in the management of hand-foot skin reaction caused by multikinase inhibitors. Commun Oncol. 2010;7:23–9.CrossRef
13.
Zurück zum Zitat Grothey A, Sobrero AF, Siena, 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. 2013;31(15_suppl):3637. Grothey A, Sobrero AF, Siena, 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. 2013;31(15_suppl):3637.
14.
Zurück zum Zitat Grothey A, George S, van Cutsem E, Blay J-Y, Sobrero A, Demetri GD. Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. Oncologist. 2014;19:669–80.CrossRefPubMedPubMedCentral Grothey A, George S, van Cutsem E, Blay J-Y, Sobrero A, Demetri GD. Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. Oncologist. 2014;19:669–80.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Xue W-S, Men S-Y, Liu W, Liu R-H. A meta-analysis of safety and efficacy of regorafenib for refractory metastatic colorectal cancer. Medicine (Baltimore). 2018;97:e12635.CrossRef Xue W-S, Men S-Y, Liu W, Liu R-H. A meta-analysis of safety and efficacy of regorafenib for refractory metastatic colorectal cancer. Medicine (Baltimore). 2018;97:e12635.CrossRef
16.
Zurück zum Zitat Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.CrossRefPubMedPubMedCentral Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Li J, Qin S, Xu R, 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. 2015;16:619–29.CrossRefPubMed Li J, Qin S, Xu R, 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. 2015;16:619–29.CrossRefPubMed
18.
Zurück zum Zitat Tanioka H, Miyamoto Y, Tsuji A, et al. Prophylactic effect of dexamethasone on regorafenib-related fatigue and/or malaise: a randomized, placebo-controlled, double-blind clinical study in patients with unresectable metastatic colorectal cancer (KSCC1402/HGCSG1402). Oncology. 2018;94:289–96.CrossRefPubMed Tanioka H, Miyamoto Y, Tsuji A, et al. Prophylactic effect of dexamethasone on regorafenib-related fatigue and/or malaise: a randomized, placebo-controlled, double-blind clinical study in patients with unresectable metastatic colorectal cancer (KSCC1402/HGCSG1402). Oncology. 2018;94:289–96.CrossRefPubMed
20.
Zurück zum Zitat Ota Y, Yuki S, Harada K, et al. Updated analysis: a retrospective cohort study evaluating the safety and efficacy of regorafenib in patients with metastatic colorectal cancer—HGCSG1401. J Clin Oncol. 2017;35:778.CrossRef Ota Y, Yuki S, Harada K, et al. Updated analysis: a retrospective cohort study evaluating the safety and efficacy of regorafenib in patients with metastatic colorectal cancer—HGCSG1401. J Clin Oncol. 2017;35:778.CrossRef
21.
Zurück zum Zitat Sánchez Gundín J. Regorafenib: effectiveness and safety in the treatment of metastatic colorectal cancer. Eur J Clin Pharm. 2017;19:7–15. Sánchez Gundín J. Regorafenib: effectiveness and safety in the treatment of metastatic colorectal cancer. Eur J Clin Pharm. 2017;19:7–15.
22.
Zurück zum Zitat Hasan T. Canadian experience managing dose intensity of regorafenib in relation to safety and clinical outcome in metastatic colorectal cancer patients. J Clin Oncol. 2016;34(15_suppl):e15154. Hasan T. Canadian experience managing dose intensity of regorafenib in relation to safety and clinical outcome in metastatic colorectal cancer patients. J Clin Oncol. 2016;34(15_suppl):e15154.
23.
Zurück zum Zitat Moriwaki T, Fukuoka S, Taniguchi H, et al. Propensity score analysis of regorafenib versus trifluridine/tipiracil in patients with metastatic colorectal cancer refractory to standard chemotherapy (REGOTAS): a Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study. Oncologist. 2018;23:7–15.CrossRefPubMed Moriwaki T, Fukuoka S, Taniguchi H, et al. Propensity score analysis of regorafenib versus trifluridine/tipiracil in patients with metastatic colorectal cancer refractory to standard chemotherapy (REGOTAS): a Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study. Oncologist. 2018;23:7–15.CrossRefPubMed
24.
Zurück zum Zitat Nannini M, Nigro MC, Vincenzi B, et al. Personalization of regorafenib treatment in metastatic gastrointestinal stromal tumours in real-life clinical practice. Ther Adv Med Oncol. 2017;9:731–9.CrossRefPubMedPubMedCentral Nannini M, Nigro MC, Vincenzi B, et al. Personalization of regorafenib treatment in metastatic gastrointestinal stromal tumours in real-life clinical practice. Ther Adv Med Oncol. 2017;9:731–9.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Higashihara Y, Serizawa N, Kato J, et al. Management tips for the low incidence, of adverse events and well efficacy of regorafenib for metastatic colorectal cancer in Juntendo University Medical Hospital. J Clin Oncol. 2015;33:778.CrossRef Higashihara Y, Serizawa N, Kato J, et al. Management tips for the low incidence, of adverse events and well efficacy of regorafenib for metastatic colorectal cancer in Juntendo University Medical Hospital. J Clin Oncol. 2015;33:778.CrossRef
26.
Zurück zum Zitat Fukuoka S, Shitara K, Itagaki M, et al. O2-5-3 safety and efficacy of regorafenib in National Cancer Center Hospital East (NCCHE). Ann Oncol. 2014;25:v61.CrossRef Fukuoka S, Shitara K, Itagaki M, et al. O2-5-3 safety and efficacy of regorafenib in National Cancer Center Hospital East (NCCHE). Ann Oncol. 2014;25:v61.CrossRef
28.
Zurück zum Zitat Komori A, Taniguchi H, Hamauchi S, et al. Serum CA19-9 response is an early predictive marker of efficacy of regorafenib in refractory metastatic colorectal cancer. Oncology. 2017;93:329–35.CrossRefPubMed Komori A, Taniguchi H, Hamauchi S, et al. Serum CA19-9 response is an early predictive marker of efficacy of regorafenib in refractory metastatic colorectal cancer. Oncology. 2017;93:329–35.CrossRefPubMed
29.
Zurück zum Zitat Lam K-O, Lee K-C, Chiu J, et al. The real-world use of regorafenib for metastatic colorectal cancer: multicentre analysis of treatment pattern and outcomes in Hong Kong. Postgrad Med J. 2017;93:395–400.CrossRefPubMed Lam K-O, Lee K-C, Chiu J, et al. The real-world use of regorafenib for metastatic colorectal cancer: multicentre analysis of treatment pattern and outcomes in Hong Kong. Postgrad Med J. 2017;93:395–400.CrossRefPubMed
30.
Zurück zum Zitat Maruzzo M, Kollar A, Benson C, et al. Regorafenib treatment for advanced, refractory gastrointestinal stromal tumor: a report of the UK managed access program. J Clin Oncol. 2014;4:10551.CrossRef Maruzzo M, Kollar A, Benson C, et al. Regorafenib treatment for advanced, refractory gastrointestinal stromal tumor: a report of the UK managed access program. J Clin Oncol. 2014;4:10551.CrossRef
31.
Zurück zum Zitat Karthaus S, Falcone A, Van Cutsem, et al. Regorafenib dose modifications in patients with metastatic colorectal cancer in the phase III CORRECT study. Oncol Res Treat. 2014;37:39. Karthaus S, Falcone A, Van Cutsem, et al. Regorafenib dose modifications in patients with metastatic colorectal cancer in the phase III CORRECT study. Oncol Res Treat. 2014;37:39.
32.
Zurück zum Zitat Dayani P. Drug safety data of regorafenib in metastatic colorectal cancer. Int J Clin Pharm. 2013;35:1251–351.CrossRef Dayani P. Drug safety data of regorafenib in metastatic colorectal cancer. Int J Clin Pharm. 2013;35:1251–351.CrossRef
33.
Zurück zum Zitat Fukuoka S, Shitara K, Noguchi M, et al. Prophylactic use of oral dexamethasone to alleviate fatigue during regorafenib treatment for patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2017;16:e39–44.CrossRefPubMed Fukuoka S, Shitara K, Noguchi M, et al. Prophylactic use of oral dexamethasone to alleviate fatigue during regorafenib treatment for patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2017;16:e39–44.CrossRefPubMed
35.
Zurück zum Zitat Doi A, Kuboki Y, Shitara K, et al. Gastrointestinal perforation and fistula formation in 5 patients with colorectal cancer during treatment with regorafenib. Clin Colorectal Cancer. 2017;16:e109–13.CrossRef Doi A, Kuboki Y, Shitara K, et al. Gastrointestinal perforation and fistula formation in 5 patients with colorectal cancer during treatment with regorafenib. Clin Colorectal Cancer. 2017;16:e109–13.CrossRef
36.
Zurück zum Zitat Argilés G, Saunders MP, Rivera F, et al. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: a phase II trial. Eur J Cancer. 2015;51:942–9.CrossRefPubMed Argilés G, Saunders MP, Rivera F, et al. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: a phase II trial. Eur J Cancer. 2015;51:942–9.CrossRefPubMed
37.
Zurück zum Zitat Son MK, Ryu M-H, Park JO, et al. Efficacy and safety of regorafenib in Korean patients with advanced gastrointestinal stromal tumor after failure of imatinib and sunitinib: a multicenter study based on the management access program. Cancer Res Treat. 2017;49:350–7.CrossRefPubMed Son MK, Ryu M-H, Park JO, et al. Efficacy and safety of regorafenib in Korean patients with advanced gastrointestinal stromal tumor after failure of imatinib and sunitinib: a multicenter study based on the management access program. Cancer Res Treat. 2017;49:350–7.CrossRefPubMed
38.
Zurück zum Zitat George S, Wang Q, Heinrich MC, et al. Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol. 2012;30:2401–7.CrossRefPubMedPubMedCentral George S, Wang Q, Heinrich MC, et al. Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol. 2012;30:2401–7.CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat Strumberg D, Scheulen ME, Schultheis B, et al. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. Br J Cancer. 2012;106:1722–7.CrossRefPubMedPubMedCentral Strumberg D, Scheulen ME, Schultheis B, et al. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. Br J Cancer. 2012;106:1722–7.CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Del Prete S, Cennamo G, Leo L, et al. Adherence and safety of regorafenib for patients with metastatic colorectal cancer: observational real-life study. Future Oncol. 2017;13:415–23.CrossRefPubMed Del Prete S, Cennamo G, Leo L, et al. Adherence and safety of regorafenib for patients with metastatic colorectal cancer: observational real-life study. Future Oncol. 2017;13:415–23.CrossRefPubMed
42.
Zurück zum Zitat Uetake H, Sugihara K, Muro K, Sunaya T, Horiuchi-Yamamoto Y, Takikawa H. Clinical features of regorafenib-induced liver injury in Japanese patients from postmarketing experience. Clin Colorectal Cancer. 2018;17:e49–58.CrossRefPubMed Uetake H, Sugihara K, Muro K, Sunaya T, Horiuchi-Yamamoto Y, Takikawa H. Clinical features of regorafenib-induced liver injury in Japanese patients from postmarketing experience. Clin Colorectal Cancer. 2018;17:e49–58.CrossRefPubMed
43.
Zurück zum Zitat Belum VR, Wu S, Lacouture ME. Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Investig New Drugs. 2013;31:1078–86.CrossRef Belum VR, Wu S, Lacouture ME. Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Investig New Drugs. 2013;31:1078–86.CrossRef
44.
Zurück zum Zitat Gomez P, Lacouture ME. Clinical presentation and management of hand-foot skin reaction associated with sorafenib in combination with cytotoxic chemotherapy: experience in breast cancer. Oncologist. 2011;16:1508–19.CrossRefPubMedPubMedCentral Gomez P, Lacouture ME. Clinical presentation and management of hand-foot skin reaction associated with sorafenib in combination with cytotoxic chemotherapy: experience in breast cancer. Oncologist. 2011;16:1508–19.CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Gyawali B, Prasad V. Health policy: me-too drugs with limited benefits—the tale of regorafenib for HCC. Nat Rev Clin Oncol. 2017;14:653–4.CrossRefPubMed Gyawali B, Prasad V. Health policy: me-too drugs with limited benefits—the tale of regorafenib for HCC. Nat Rev Clin Oncol. 2017;14:653–4.CrossRefPubMed
46.
Zurück zum Zitat Mahipal A, Denson AC, Djulbegovic B, et al. Effect of age on clinical outcomes in phase 1 trial participants. Cancer Control. 2015;22:235–41.CrossRefPubMed Mahipal A, Denson AC, Djulbegovic B, et al. Effect of age on clinical outcomes in phase 1 trial participants. Cancer Control. 2015;22:235–41.CrossRefPubMed
47.
Zurück zum Zitat Mross K, Frost A, Steinbild S, 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.CrossRefPubMed Mross K, Frost A, Steinbild S, 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.CrossRefPubMed
48.
Zurück zum Zitat Bekaii-Saab TS, Ou F-S, Anderson DM, et al. Regorafenib dose optimization study (ReDOS): randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC). An ACCRU network study. J Clin Oncol. 2018;36(4_suppl):611.CrossRef Bekaii-Saab TS, Ou F-S, Anderson DM, et al. Regorafenib dose optimization study (ReDOS): randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC). An ACCRU network study. J Clin Oncol. 2018;36(4_suppl):611.CrossRef
49.
Zurück zum Zitat Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:56–66.CrossRefPubMed Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:56–66.CrossRefPubMed
50.
Zurück zum Zitat Bruix J, Tak W-Y, Gasbarrini A, et al. Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. Eur J Cancer. 2013;49:3412–9.CrossRefPubMed Bruix J, Tak W-Y, Gasbarrini A, et al. Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. Eur J Cancer. 2013;49:3412–9.CrossRefPubMed
51.
Zurück zum Zitat Osawa H. Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer. Mol Clin Oncol. 2017;6:365–72.CrossRefPubMedPubMedCentral Osawa H. Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer. Mol Clin Oncol. 2017;6:365–72.CrossRefPubMedPubMedCentral
53.
Zurück zum Zitat Bayer HealthCare. Understanding and managing adverse events in your Stivarga (regorafenib) treated patients: a guide for healthcare providers. Whippany, NJ: Bayer HealthCare. Bayer HealthCare. Understanding and managing adverse events in your Stivarga (regorafenib) treated patients: a guide for healthcare providers. Whippany, NJ: Bayer HealthCare.
55.
Zurück zum Zitat Nardone B, Hensley JR, Kulik L, et al. The effect of hand-foot skin reaction associated with the multikinase inhibitors sorafenib and sunitinib on health-related quality of life. J Drugs Dermatol. 2012;11:e61–5.PubMed Nardone B, Hensley JR, Kulik L, et al. The effect of hand-foot skin reaction associated with the multikinase inhibitors sorafenib and sunitinib on health-related quality of life. J Drugs Dermatol. 2012;11:e61–5.PubMed
56.
Zurück zum Zitat Wang Z, Xu J, Nie W, Huang G, Tang J, Guan X. Risk of hypertension with regorafenib in cancer patients: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2014;70:225–31.CrossRefPubMed Wang Z, Xu J, Nie W, Huang G, Tang J, Guan X. Risk of hypertension with regorafenib in cancer patients: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2014;70:225–31.CrossRefPubMed
Metadaten
Titel
Meta-Analysis of Regorafenib-Associated Adverse Events and Their Management in Colorectal and Gastrointestinal Stromal Cancers
verfasst von
Ganfeng Xie
Yuzhu Gong
Shuang Wu
Chong Li
Songtao Yu
Zhe Wang
Jianfang Chen
Quanfeng Zhao
Jianjun Li
Houjie Liang
Publikationsdatum
17.06.2019
Verlag
Springer Healthcare
Erschienen in
Advances in Therapy / Ausgabe 8/2019
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-019-01013-5

Weitere Artikel der Ausgabe 8/2019

Advances in Therapy 8/2019 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.