Korean J Urol.  2015 Dec;56(12):791-795. 10.4111/kju.2015.56.12.791.

Influence of vascular endothelial growth factor inhibition on simple renal cysts in patients receiving bevacizumab-based chemotherapy

• Grenader T
• Shavit L

• KMID: 2359870
• DOI: http://doi.org/10.4111/kju.2015.56.12.791

Abstract

PURPOSE
Although angiogenesis has been implicated in the promotion of renal cyst growth in autosomal dominant polycystic kidney disease, no studies have investigated the role of angiogenesis in the growth of simple renal cysts. The aim of current study was to investigate the effect of chemotherapy with the antivascular endothelial growth factor antibody bevacizumab on renal cyst development and growth in cancer patients.
MATERIALS AND METHODS
We retrospectively reviewed the medical records of 136 patients with a variety of cancers that were treated with bevacizumab-based chemotherapy for metastatic disease. The presence of and changes in renal cysts were evaluated by retrospective analysis of computed tomography scans performed for assessment of tumor response to bevacizumab-based therapy.
RESULTS
The median age of the patients was 64 years. Renal cysts were identified in 66 patients, in whom 33 (50%) had a single cyst and the rest had 2 or more cysts. The average dose of bevacizumab was 2.68 mg/kg per week. Median duration of treatment was 33 weeks. Average cyst size was 1.9±2.4 cm at the beginning of the study and the majority of the cysts (54 patients, 84%) did not change in size or shape during bevacizumab treatment. No patients were identified with new cysts. Cyst size changed in 10 patients (16%): an increase of 15% to 40% from the baseline size in 5 patients and a decrease in size of 10% to 70% in another 5 patients. The duration of bevacizumab therapy was significantly longer in the subgroup of patients with diminished or increased cyst size than in the patients with stable cyst size: 62 weeks versus 29 weeks, respectively (p=0.0002).
CONCLUSIONS
Our data demonstrated that simple renal cysts were stable in size and number in the vast majority of cancer patients treated with bevacizumab.

Keyword

Angiogenesis inhibitors; Bevacizumab; Cysts; Vascular endothelial growth factor receptors

MeSH Terms

Adult
Aged
Aged, 80 and over
Angiogenesis Inhibitors/administration & dosage/*therapeutic use
Bevacizumab/administration & dosage/*therapeutic use
Cysts/complications/*drug therapy/pathology
Disease Progression
Dose-Response Relationship, Drug
Drug Evaluation/methods
Female
Humans
Kidney Diseases/complications/*drug therapy/pathology
Male
Middle Aged
Neoplasms/complications/drug therapy
Retrospective Studies
Vascular Endothelial Growth Factor A/*antagonists & inhibitors
Angiogenesis Inhibitors
Bevacizumab
Vascular Endothelial Growth Factor A

Reference

1. Persson AB, Buschmann IR. Vascular growth in health and disease. Front Mol Neurosci. 2011; 4:14.

2. Wei W, Popov V, Walocha JA, Wen J, Bello-Reuss E. Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys: a corrosion cast study. Kidney Int. 2006; 70:1261–1268.

3. Reed BY, Masoumi A, Elhassan E, McFann K, Cadnapaphornchai MA, Maahs DM, et al. Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease. Kidney Int. 2011; 79:128–134.

4. Bello-Reuss E, Holubec K, Rajaraman S. Angiogenesis in autosomal-dominant polycystic kidney disease. Kidney Int. 2001; 60:37–45.

5. Los M, Aarsman CJ, Terpstra L, Wittebol-Post D, Lips CJ, Blijham GH, et al. Elevated ocular levels of vascular endothelial growth factor in patients with von Hippel-Lindau disease. Ann Oncol. 1997; 8:1015–1022.

6. Tao Y, Kim J, Yin Y, Zafar I, Falk S, He Z, et al. VEGF receptor inhibition slows the progression of polycystic kidney disease. Kidney Int. 2007; 72:1358–1366.

7. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350:2335–2342.

8. Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol. 2005; 23:3697–3705.

9. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009; 27:1227–1234.

10. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007; 357:2666–2676.

11. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008; 26:5422–5428.

12. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009; 27:4733–4740.

13. Bosniak MA. The current radiological approach to renal cysts. Radiology. 1986; 158:1–10.

14. Cobo RM, Bittencourt LK. History and importance of the Bosniak classification for complex renal cysts. Radiol Bras. 2014; 47:IX.

15. Ravine D, Gibson RN, Donlan J, Sheffield LJ. An ultrasound renal cyst prevalence survey: specificity data for inherited renal cystic diseases. Am J Kidney Dis. 1993; 22:803–807.

16. Terada N, Ichioka K, Matsuta Y, Okubo K, Yoshimura K, Arai Y. The natural history of simple renal cysts. J Urol. 2002; 167:21–23.

17. Terada N, Arai Y, Kinukawa N, Terai A. The 10-year natural history of simple renal cysts. Urology. 2008; 71:7–11.

18. Dalton D, Neiman H, Grayhack JT. The natural history of simple renal cysts: a preliminary study. J Urol. 1986; 135:905–908.

19. Yasuda M, Masai M, Shimazaki J. A simple renal cyst. Nihon Hinyokika Gakkai Zasshi. 1993; 84:251–257.

20. Bowers DL, Ikeguchi EF, Sawczuk IS. Transition from renal cyst to a renal carcinoma detected by ultrasonography. Br J Urol. 1997; 80:495–496.

21. Rule AD, Sasiwimonphan K, Lieske JC, Keddis MT, Torres VE, Vrtiska TJ. Characteristics of renal cystic and solid lesions based on contrast-enhanced computed tomography of potential kidney donors. Am J Kidney Dis. 2012; 59:611–618.

22. Chin HJ, Ro H, Lee HJ, Na KY, Chae DW. The clinical significances of simple renal cyst: is it related to hypertension or renal dysfunction? Kidney Int. 2006; 70:1468–1473.

23. Pedersen JF, Emamian SA, Nielsen MB. Significant association between simple renal cysts and arterial blood pressure. Br J Urol. 1997; 79:688–691.

24. Holmberg G, Hietala SO, Karp K, Ohberg L. Significance of simple renal cysts and percutaneous cyst puncture on renal function. Scand J Urol Nephrol. 1994; 28:35–38.

25. Al-Said J, Brumback MA, Moghazi S, Baumgarten DA, O'Neill WC. Reduced renal function in patients with simple renal cysts. Kidney Int. 2004; 65:2303–2308.

26. Papanicolaou N, Pfister RC, Yoder IC. Spontaneous and traumatic rupture of renal cysts: diagnosis and outcome. Radiology. 1986; 160:99–103.

27. Sakai N, Kanda F, Kondo K, Fukuoka H, Tanaka T. Sonographically detected malignant transformation of a simple renal cyst. Int J Urol. 2001; 8:23–25.

28. Nishibuchi S, Suzuki Y, Okada K. A case report of renal cell carcinoma in a renal cyst. Hinyokika Kiyo. 1992; 38:181–184.