Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2017

Open Access 01-12-2017 | Research

Combined high dose radiation and pazopanib in metastatic renal cell carcinoma: a phase I dose escalation trial

Authors: Katrien De Wolf, Sylvie Rottey, Karim Vermaelen, Karel Decaestecker, Nora Sundahl, Lizzy De Lobel, Els Goetghebeur, Gert De Meerleer, Nicolaas Lumen, Valérie Fonteyne, Daan De Maeseneer, Piet Ost

Published in: Radiation Oncology | Issue 1/2017

Login to get access

Abstract

Background

The primary objective was to determine maximum tolerated radiation dose in patients with metastatic renal cell carcinoma on pazopanib treatment.

Methods

Treatment-naïve patients received pazopanib according to standard of care. Stereotactic body radiotherapy (SBRT) was delivered concurrently to the largest metastatic lesion at day 8, 10 and 12. SBRT doses were escalated in 3 dose levels (24 Gy/3, 30 Gy/3 and 36 Gy/3). Dose level was assigned using Time-to-Event Continual Reassessment Method with the target dose-limiting toxicity rate set to 0.25.

Results

Thirteen patients were included. One patient experienced dose limiting toxicity (DLT) at dose level 3 (grade 4 hypoglycemia). Maximum tolerated dose was not reached with a recommended dose of 36 Gy/3 having a probability of DLT of 11%. One-year local control was 83% (95% confidence interval 61–100) and 1-year progression-free survival was 28% (95% confidence interval 1–55).

Conclusions

SBRT in combination with pazopanib is well tolerated with good local control and response rates outside the radiation field.

Trial registration

This trial was retrospectively registered on clinicaltrials.gov(NCT02334709) on January 6th, 2015.
Appendix
Available only for authorised users
Literature
1.
Audenet F, Yates DR, Cancel-Tassin G, Cussenot O, Roupret M. Genetic pathways involved in carcinogenesis of clear cell renal cell carcinoma: genomics towards personalized medicine. BJU Int. 2012;109:1864–70.CrossRefPubMed
2.
3.
Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, Patard JJ, Mulders PF, Sinescu IC. European Association of Urology Guideline G: EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol. 2010;58:398–406.CrossRefPubMed
4.
Coppin C, Le L, Porzsolt F, Wilt T. Targeted therapy for advanced renal cell carcinoma. Cochrane Database Syst Rev. 2008:CD006017.
5.
Iacovelli R, Alesini D, Palazzo A, Trenta P, Santoni M, De Marchis L, Cascinu S, Naso G, Cortesi E. Targeted therapies and complete responses in first line treatment of metastatic renal cell carcinoma. A meta-analysis of published trials. Cancer Treat Rev. 2014;40:271–5.CrossRefPubMed
6.
Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373:1803–13.CrossRefPubMed
7.
De Wolf K, Vermaelen K, De Meerleer G, Lambrecht BN, Ost P. The potential of radiotherapy to enhance the efficacy of renal cell carcinoma therapy. Oncoimmunology. 2015;4:e1042198.CrossRefPubMedPubMedCentral
8.
Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369:722–31.CrossRefPubMed
9.
Tree AC, Khoo VS, Eeles RA, Ahmed M, Dearnaley DP, Hawkins MA, Huddart RA, Nutting CM, Ostler PJ, van As NJ. Stereotactic body radiotherapy for oligometastases. Lancet Oncol. 2013;14:e28–37.CrossRefPubMed
10.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
11.
12.
Salama JK, Hasselle MD, Chmura SJ, Malik R, Mehta N, Yenice KM, Villaflor VM, Stadler WM, Hoffman PC, Cohen EE, et al. Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease. Cancer. 2012;118:2962–70.CrossRefPubMed
13.
Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, Keall P, Lovelock M, Meeks S, Papiez L, et al. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010;37:4078–101.CrossRefPubMed
14.
Cheung YK, Chappell R. Sequential designs for phase I clinical trials with late-onset toxicities. Biometrics. 2000;56:1177–82.CrossRefPubMed
15.
De Meerleer G, Khoo V, Escudier B, Joniau S, Bossi A, Ost P, Briganti A, Fonteyne V, Van Vulpen M, Lumen N, et al. Radiotherapy for renal-cell carcinoma. Lancet Oncol. 2014;15:e170–7.CrossRefPubMed
16.
Miller JA, Balagamwala EH, Angelov L, Suh JH, Rini B, Garcia JA, Ahluwalia M, Chao ST. Spine stereotactic radiosurgery with concurrent tyrosine kinase inhibitors for metastatic renal cell carcinoma. J Neurosurg Spine. 2016;25:766–74.CrossRefPubMed
17.
Ranck MC, Golden DW, Corbin KS, Hasselle MD, Liauw SL, Stadler WM, Hahn OM, Weichselbaum RR, Salama JK. Stereotactic body radiotherapy for the treatment of oligometastatic renal cell carcinoma. Am J Clin Oncol. 2013;36:589–95.CrossRefPubMed
18.
Altoos B, Amini A, Yacoub M, Bourlon MT, Kessler EE, Flaig TW, Fisher CM, Kavanagh BD, Lam ET, Karam SD. Local Control Rates of Metastatic Renal Cell Carcinoma (RCC) to Thoracic, Abdominal, and Soft Tissue Lesions Using Stereotactic Body Radiotherapy (SBRT). Radiat Oncol. 2015;10:218.CrossRefPubMedPubMedCentral
19.
Svedman C, Sandstrom P, Pisa P, Blomgren H, Lax I, Kalkner KM, Nilsson S, Wersall P. A prospective Phase II trial of using extracranial stereotactic radiotherapy in primary and metastatic renal cell carcinoma. Acta Oncol. 2006;45:870–5.CrossRefPubMed
20.
Ghia AJ, Chang EL, Bishop AJ, Pan HY, Boehling NS, Amini B, Allen PK, Li J, Rhines LD, Tannir NM, et al. Single-fraction versus multifraction spinal stereotactic radiosurgery for spinal metastases from renal cell carcinoma: secondary analysis of Phase I/II trials. J Neurosurg Spine. 2016;24:829–36.CrossRefPubMed
21.
Ponsky L, Lo SS, Zhang Y, Schluchter M, Liu Y, Patel R, Abouassaly R, Welford S, Gulani V, Haaga JR, et al. Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma. Radiother Oncol. 2015;117:183–7.CrossRefPubMed
22.
Kothari G, Foroudi F, Gill S, Corcoran NM, Siva S. Outcomes of stereotactic radiotherapy for cranial and extracranial metastatic renal cell carcinoma: a systematic review. Acta Oncol. 2015;54:148–57.CrossRefPubMed
23.
Porta C, Paglino C, Imarisio I, Ganini C, Pedrazzoli P. Immunological effects of multikinase inhibitors for kidney cancer: a clue for integration with cellular therapies? J Cancer. 2011;2:333–8.CrossRefPubMedPubMedCentral
24.
Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H. Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res. 2009;69:2506–13.CrossRefPubMedPubMedCentral
25.
Goyal S, Shah S, Khan AJ, Danish H, Haffty BG. Evaluation of acute locoregional toxicity in patients with breast cancer treated with adjuvant radiotherapy in combination with pazopanib. ISRN Oncol. 2012;2012:896202.PubMedPubMedCentral
26.
Haas RL, Gelderblom H, Sleijfer S, van Boven HH, Scholten A, Dewit L, Borst G, van der Hage J, Kerst JM, Nout RA, et al. A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities. Acta Oncol. 2015;54:1195–201.CrossRefPubMed
27.
Barney BM, Markovic SN, Laack NN, Miller RC, Sarkaria JN, Macdonald OK, Bauer HJ, Olivier KR. Increased bowel toxicity in patients treated with a vascular endothelial growth factor inhibitor (VEGFI) after stereotactic body radiation therapy (SBRT). Int J Radiat Oncol Biol Phys. 2013;87:73–80.CrossRefPubMed
28.
Punt S, Fleuren GJ, Kritikou E, Lubberts E, Trimbos JB, Jordanova ES, Gorter A. Angels and demons: Th17 cells represent a beneficial response, while neutrophil IL-17 is associated with poor prognosis in squamous cervical cancer. Oncoimmunology. 2015;4:e984539.CrossRefPubMedPubMedCentral
29.
Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG. Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res. 2008;14:3254–61.CrossRefPubMedPubMedCentral
30.
von Euw E, Chodon T, Attar N, Jalil J, Koya RC, Comin-Anduix B, Ribas A. CTLA4 blockade increases Th17 cells in patients with metastatic melanoma. J Transl Med. 2009;7:35.CrossRefPubMedPubMedCentral
31.
Lee Y, Awasthi A, Yosef N, Quintana FJ, Xiao S, Peters A, Wu C, Kleinewietfeld M, Kunder S, Hafler DA, et al. Induction and molecular signature of pathogenic TH17 cells. Nat Immunol. 2012;13:991–9.CrossRefPubMedPubMedCentral
32.
Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342:971–6.CrossRefPubMedPubMedCentral
33.
Metadata
Title
Combined high dose radiation and pazopanib in metastatic renal cell carcinoma: a phase I dose escalation trial
Authors
Katrien De Wolf
Sylvie Rottey
Karim Vermaelen
Karel Decaestecker
Nora Sundahl
Lizzy De Lobel
Els Goetghebeur
Gert De Meerleer
Nicolaas Lumen
Valérie Fonteyne
Daan De Maeseneer
Piet Ost
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2017
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-017-0893-x

Other articles of this Issue 1/2017

Radiation Oncology 1/2017 Go to the issue

Research

Factors affecting survival after concurrent chemoradiation therapy for advanced hepatocellular carcinoma: a retrospective study

Research

First intraindividual comparison of contrast-enhanced MRI, FET- and DOTATOC- PET in patients with intracranial meningiomas

Research

Expert consensus on re-irradiation for recurrent glioma

Research

Analyses of distribution and dosimetry of brain metastases in small cell lung cancer with relation to the neural stem cell regions: feasibility of sparing the hippocampus in prophylactic cranial irradiation

Research

Is pulmonary artery a dose-limiting organ at risk in non-small cell lung cancer patients treated with definitive radiotherapy?

Research

Cell-in-cell structures are more potent predictors of outcome than senescence or apoptosis in head and neck squamous cell carcinomas