Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: Results of a multicenter, phase Ib study

Annals of Oncology

Volumn 24, Issue 6, 2013, Pages 1560-1567

  Schultheis, B ^a   Folprecht, G ^b   Kuhlmann, J ^c   Ehrenberg, R ^d   Hacker, U T ^e   Kohne C H ^f   Kornacker, M ^g   Boix, O ^g   Lettieri, J ^h   Krauss, J ^d   Fischer, R ⁱ   Hamann, S ^b   Strumberg, D ^a   Mross, K B ^j  

^a RUHR UNIVERSITY BOCHUM   (Germany)

^b UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^c UNIVERSITY OF FREIBURG   (Germany)

^d UNIVERSITY OF HEIDELBERG   (Germany)

^e UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^f Clinic Oldenburg   (Germany)

^g BAYER PHARMA AG   (Germany)

^h Global Biologics Research   (United States)

ⁱ Specialist Oncology Center   (Germany)

^j UNIVERSITY OF FREIBURG   (Germany)

more..

Author keywords

Chemotherapy; Colorectal cancer; Combination therapy; Regorafenib; Tyrosine kinase inhibition

Indexed keywords

FIRTECAN; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; OXALIPLATIN; REGORAFENIB;

ABDOMINAL PAIN; ADULT; AGED; ALOPECIA; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; BRAIN ISCHEMIA; CANCER COMBINATION CHEMOTHERAPY; CANCER CONTROL; CHEMOTHERAPY INDUCED ANEMIA; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; CLINICAL ARTICLE; COUGHING; DESQUAMATION; DIARRHEA; DIZZINESS; DOSE RESPONSE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EMPYEMA; EPISTAXIS; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FLATULENCE; GASTROINTESTINAL SYMPTOM; HAND FOOT SYNDROME; HEARTBURN; HUMAN; HYPERTENSION; HYPOKALEMIA; HYPOPHOSPHATEMIA; LEUKOPENIA; LIVER FAILURE; MALE; MAXIMUM PLASMA CONCENTRATION; METASTATIC COLORECTAL CANCER; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MUSCULOSKELETAL DISEASE; NEUTROPENIA; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PNEUMONIA; PRIORITY JOURNAL; SENSORY NEUROPATHY; SIDE EFFECT; SKIN DISEASE; SOFT TISSUE DISEASE; THROMBOCYTOPENIA; THROMBOEMBOLISM; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; VOICE CHANGE; WEIGHT REDUCTION;

CHEMOTHERAPY; COLORECTAL CANCER; COMBINATION THERAPY; REGORAFENIB; TYROSINE KINASE INHIBITION;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CAMPTOTHECIN; COLORECTAL NEOPLASMS; FEMALE; FLUOROURACIL; HUMANS; LEUCOVORIN; MALE; MIDDLE AGED; ORGANOPLATINUM COMPOUNDS; PHENYLUREA COMPOUNDS; PYRIDINES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84878442416     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdt056     Document Type: Article

References (37)

1. Globocan. Colorectal Cancer Fact Sheet 2008. Lyon, France: International Agency for Research on Cancer 2010.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Colon Cancer. Version 3.2012. Fort Washington, PA: National Comprehensive Cancer Network 2012.
3. Van Cutsem E, Nordlinger B, Cervantes A. Advanced colorectal cancer: ESMO clinical practice guidelines for treatment. Ann Oncol 2010; 21(Suppl 2): v93-v97.
4. Sanoff HK, Sargent DJ, Campbell ME et al. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol 2008; 26: 5721-5727.
5. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-2342.
6. Van Cutsem E, Rivera F, Berry S et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 2009; 20: 1842-1847.
7. Ocvirk J, Brodowicz T, Wrba F et al. Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial. World J Gastroenterol 2010; 16: 3133-3143.
8. Meyerhardt JA, Stuart K, Fuchs CS et al. Phase II study of FOLFOX, bevacizumab and erlotinib as first-line therapy for patients with metastatic colorectal cancer. Ann Oncol 2007; 18: 1185-1189.
9. Tol J, Koopman M, Cat M et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 2009; 360: 563-572.
10. 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: 245-255.
11. 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: 2658-2667.
12. 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: 1722-1727.
13. Grothey A, Cutsem EV, Sobrero A et al. for the CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2013; 381: 303-312.
14. Schultheis B, Folprecht G, Kuhlmann J et al. Phase I study of regorafenib sequentially administered with either FOLFOX or FOLFIRI in first-/second-line colorectal cancer patients. American Society of Clinical Oncology Annual Meeting, Chicago, IL, USA, 2011; Abstract 3585.
15. Guidance for Industry. Bioanalytical Method Validation. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM); 2001.
16. Graham MA, Lockwood GF, Greenslade D et al. Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res 2000; 6: 1205-1218.
17. Tournigand C, André T, Achille E et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22: 229-237.
18. Douillard JY, Cunningham D, Roth AD et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 2000; 355: 1041-1047.
19. Shimizu T, Satoh T, Tamura K et al. Oxaliplatin/fluorouracil/leucovorin (FOLFOX4 and modified FOLFOX6) in patients with refractory or advanced colorectal cancer: post-approval Japanese population experience. Int J Clin Oncol 2007; 12: 218-223.
20. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005; 307: 58-62.
21. Ma J, Pulfer S, Li S et al. Pharmacodynamic-mediated reduction of temozolomide tumor concentrations by the angiogenesis inhibitor TNP-470. Cancer Res 2001; 61: 5491-548.
22. Fenton BM, Paoni SF, Ding I. Effect of VEGF receptor-2 antibody on vascular function and oxygenation in spontaneous and transplanted tumors. Radiother Oncol 2004; 72: 221-230.
23. Hu-Lowe D, Athias A, Hall C et al. Impact of dosing schedule and dosing sequence on anti-tumor efficacy of combination therapy with the antiangiogenic agent (AA) axitinib (AG-013736) in xenograft tumor models of human pancreatic carcinoma and non-small cell lung cancer (NSCLC). AACR Annual Meeting 2009; Denver: American Association for Cancer Research, Abstract 144.
24. Troiani T, Serkova NJ, Gustafson DL et al. Investigation of two dosing schedules of vandetanib (ZD6474), an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling in combination with irinotecan in a human colon cancer xenograft model. Clin Cancer Res 2007; 13: 6450-6458.
25. Christensen JG. Antitumor efficacy of sunitinib malate in concurrent and sequential combinations with standard chemotherapeutic agents in non-small cell lung cancer (NSCLC) nonclinical models. AACR Annual Meeting 2009; Denver: American Association for Cancer Research, Abstract 1433.
26. Starling N, Vázquez-Mazón F, Cunningham D et al. A phase I study of sunitinib in combination with FOLFIRI in patients with untreated metastatic colorectal cancer. Ann Oncol 2012; 23: 119-127.
27. Mross K, Büchert M, Fasol U et al. A preliminary report of a phase II study of folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) plus sunitinib with toxicity, efficacy, pharmacokinetics, biomarker, imaging data in patients with colorectal cancer with liver metastases as 1st line treatment-a study of the CESAR Central European Society for Anticancer Drug Research. Int J Clin Pharmacol Ther 2011; 49: 96-98.
28. ClinicalTrials.gov. Study of FOLFIRI Chemotherapy with or without Sunitinib in Patients with Metastatic Colorectal Cancer. http://www.clinicaltrials.gov/show/ NCT00457691 (23rd August 2012, date last accessed).
29. Kupsch P, Henning BF, Passarge K et al. Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer. Clin Colorectal Cancer 2005; 5: 188-196.
30. Mross K, Steinbild S, Baas F et al. Results from an in vitro and a clinical/ pharmacological phase I study with the combination irinotecan and sorafenib. Eur J Cancer 2007; 43: 55-63.
31. Schultheis B, Kummer G, Zeth M et al. Phase Ib study of sorafenib in combination with gemcitabine and cisplatin in patients with refractory solid tumors. Cancer Chemother Pharmacol 2012; 69: 333-339.
32. Hecht JR, Trarbach T, Hainsworth JD et al. Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma. J Clin Oncol 2011; 29: 1997-2003.
33. Van Cutsem E, Bajetta E, Valle J et al. Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol. 2011; 29: 2004-2010.
34. ClinicalTrials.gov. Leucovorin and Fluorouracil with or without SU5416 in Treating Patients with Metastatic Colorectal Cancer. http://www.clinicaltrials.gov/show/ NCT00004252 (23rd August 2012, date last accessed).
35. Siu LL, Shapiro JD, Jonker DJ et al. Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients ( pts) with metastatic (MET) chemotherapy refractory K-RAS wild-type (WT) colorectal carcinoma (CRC): the NCIC Clinical Trials Group and AGITG CO.20 trial. J Clin Oncol 2012; 30 (Suppl 4): 3504.
36. Robertson JD, Botwood NA, Rothenberg ML et al. Phase III Trial of FOLFOX plus bevacizumab or cediranib (AZD2171) as first-line treatment of patients with metastatic colorectal cancer. Clin Colorectal Cancer 2009; 8: 59-60.
37. Hoff PM, Hochhaus A, Pestalozzi BC et al. Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II). J Clin Oncol 2012; 30: 3596-3603.