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Published in: Cancer Chemotherapy and Pharmacology 1/2019

01-07-2019 | Bevacizumab | Original Article

Renin–angiotensin system inhibitors for countering proteinuria induced by angiogenesis inhibitors: a retrospective observational analysis

Authors: Toshinori Hirai, Yukari Shuji, Megumi Takiyama, Kazuhiko Hanada, Toshimasa Itoh

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2019

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Abstract

Purpose

Occurrence of proteinuria could result in cessation of bevacizumab and ramucirumab treatments. Renin–angiotensin system (RAS) inhibitors exert a renoprotective effect by countering proteinuria. However, the association between renoprotective effect of RAS inhibitors and blood pressure control is unclear. This study assessed the risk factors for proteinuria induced by bevacizumab or ramucirumab and the relationship between renoprotective effect of RAS inhibitors and blood pressure control.

Methods

A retrospective observational analysis was conducted at Tokyo Women’s Medical University, Medical Center East from June 2015 to May 2018. Multivariate logistic regression analysis was used to identify risk factors for proteinuria induced by treatment with bevacizumab and ramucirumab. Renoprotective effect was assessed by analyzing blood pressure data in association with the use of RAS inhibitors.

Results

Out of 208 patients included in this study, proteinuria was observed in 50 (24%) patients. Body mass index ≥ 24 kg/m2 (OR = 2.45, 95% CI 1.21–4.96, p = 0.01), colorectal cancer (OR = 1.95, 95% CI 1.00–3.80, p < 0.05), and use of RAS inhibitors (OR = 0.25 95% CI 0.07–0.92, p = 0.04) were associated with proteinuria induced by treatment with bevacizumab and ramucirumab. A change in systolic blood pressure at second visit was higher in patients with RAS inhibitors compared with those in patients without RAS inhibitors (25 mmHg vs − 5 mmHg, p = 0.04).

Conclusion

Although RAS inhibitors protected patients from proteinuria induced by bevacizumab or ramucirumab, RAS inhibitors could not adequately control their blood pressures in patients with proteinuria.
Literature
1.
go back to reference Soria JC, Mauguen A, Reck M, Sandler AB, Saijo N, Johnson DH, Burcoveanu D, Fukuoka M, Besse B, Pignon JP (2013) Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol 24(1):20–30. https://doi.org/10.1093/annonc/mds590 CrossRefPubMed Soria JC, Mauguen A, Reck M, Sandler AB, Saijo N, Johnson DH, Burcoveanu D, Fukuoka M, Besse B, Pignon JP (2013) Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol 24(1):20–30. https://​doi.​org/​10.​1093/​annonc/​mds590 CrossRefPubMed
2.
go back to reference Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A (2014) Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15(11):1224–1235. https://doi.org/10.1016/s1470-2045(14)70420-6 CrossRefPubMed Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A (2014) Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15(11):1224–1235. https://​doi.​org/​10.​1016/​s1470-2045(14)70420-6 CrossRefPubMed
4.
go back to reference Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stahle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496. https://doi.org/10.1056/NEJMoa1103799 CrossRef Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stahle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496. https://​doi.​org/​10.​1056/​NEJMoa1103799 CrossRef
8.
go back to reference Iwasa S, Nakajima TE, Nagashima K, Honma Y, Kato K, Hamaguchi T, Yamada Y, Shimada Y (2013) Lack of association of proteinuria and clinical outcome in patients treated with bevacizumab for metastatic colorectal cancer. Anticancer Res 33(1):309–316PubMed Iwasa S, Nakajima TE, Nagashima K, Honma Y, Kato K, Hamaguchi T, Yamada Y, Shimada Y (2013) Lack of association of proteinuria and clinical outcome in patients treated with bevacizumab for metastatic colorectal cancer. Anticancer Res 33(1):309–316PubMed
12.
go back to reference Nihei S, Sato J, Harada T, Kuyama S, Suzuki T, Waga N, Saito Y, Kisara S, Yokota A, Okada K, Tsuchiya M, Terui K, Tadokoro Y, Chiba T, Kudo K, Oizumi S, Inoue A, Morikawa N (2018) Antiproteinuric effects of renin-angiotensin inhibitors in lung cancer patients receiving bevacizumab. Cancer Chemother Pharmacol 81(6):1051–1059. https://doi.org/10.1007/s00280-018-3580-1 CrossRefPubMed Nihei S, Sato J, Harada T, Kuyama S, Suzuki T, Waga N, Saito Y, Kisara S, Yokota A, Okada K, Tsuchiya M, Terui K, Tadokoro Y, Chiba T, Kudo K, Oizumi S, Inoue A, Morikawa N (2018) Antiproteinuric effects of renin-angiotensin inhibitors in lung cancer patients receiving bevacizumab. Cancer Chemother Pharmacol 81(6):1051–1059. https://​doi.​org/​10.​1007/​s00280-018-3580-1 CrossRefPubMed
15.
go back to reference Yano Y, Sato Y, Fujimoto S, Konta T, Iseki K, Moriyama T, Yamagata K, Tsuruya K, Yoshida H, Asahi K, Kurahashi I, Ohashi Y, Watanabe T (2012) Association of high pulse pressure with proteinuria in subjects with diabetes, prediabetes, or normal glucose tolerance in a large Japanese general population sample. Diabetes Care 35(6):1310–1315. https://doi.org/10.2337/dc11-2245 CrossRefPubMedPubMedCentral Yano Y, Sato Y, Fujimoto S, Konta T, Iseki K, Moriyama T, Yamagata K, Tsuruya K, Yoshida H, Asahi K, Kurahashi I, Ohashi Y, Watanabe T (2012) Association of high pulse pressure with proteinuria in subjects with diabetes, prediabetes, or normal glucose tolerance in a large Japanese general population sample. Diabetes Care 35(6):1310–1315. https://​doi.​org/​10.​2337/​dc11-2245 CrossRefPubMedPubMedCentral
20.
go back to reference Teramachi H, Shiga H, Komada N, Tamura K, Yasuda M, Umeda M, Tachi T, Goto C, Tsuchiya T (2013) Risk factors contributing to urinary protein expression resulting from bevacizumab combination chemotherapy. Pharmazie 68(3):217–220PubMed Teramachi H, Shiga H, Komada N, Tamura K, Yasuda M, Umeda M, Tachi T, Goto C, Tsuchiya T (2013) Risk factors contributing to urinary protein expression resulting from bevacizumab combination chemotherapy. Pharmazie 68(3):217–220PubMed
21.
go back to reference Yen CJ, Muro K, Kim TW, Kudo M, Shih JY, Lee KW, Chao Y, Kim SW, Yamazaki K, Sohn J, Cheng R, Zhang Y, Binder P, Mi G, Orlando M, Chung HC (2018) Ramucirumab safety in east asian patients: a meta-analysis of six global, randomized, double-blind, placebo-controlled, phase III clinical trials. J Glob Oncol 4:1–12. https://doi.org/10.1200/jgo.17.00227 CrossRefPubMed Yen CJ, Muro K, Kim TW, Kudo M, Shih JY, Lee KW, Chao Y, Kim SW, Yamazaki K, Sohn J, Cheng R, Zhang Y, Binder P, Mi G, Orlando M, Chung HC (2018) Ramucirumab safety in east asian patients: a meta-analysis of six global, randomized, double-blind, placebo-controlled, phase III clinical trials. J Glob Oncol 4:1–12. https://​doi.​org/​10.​1200/​jgo.​17.​00227 CrossRefPubMed
Metadata
Title
Renin–angiotensin system inhibitors for countering proteinuria induced by angiogenesis inhibitors: a retrospective observational analysis
Authors
Toshinori Hirai
Yukari Shuji
Megumi Takiyama
Kazuhiko Hanada
Toshimasa Itoh
Publication date
01-07-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-019-03876-5

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