Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy

Wilop, Stefan; Hobe, Sabine von; Crysandt, Martina; Esser, Albert; Osieka, R.; Jost, Edgar

doi:10.1007/s00432-009-0587-3

Cited by 151 publications

(139 citation statements)

References 34 publications

(41 reference statements)

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“…In a retrospective cohort study of advanced non-small-cell lung cancer, RAS inhibitors were statistically associated with longer survival when used with first-line platinum-based chemotherapy. (29) Cimetidine, the prototypical histamine H2 receptor antagonist, has shown antitumor activity against colon, gastric and kidney cancers and melanomas. (17) Multiple potential mechanisms have been indicated: (i) a direct inhibitory effect on tumor growth by blocking the cell-growth-promoting activity of histamine; (ii) an indirect effect by inhibiting tumor-associated angiogenesis; and (iii) a cell-mediated immunomodulation by enhancing the host's immune responses to tumor cells.…”

Section: (A) (B) (C) (D) (E) (F)mentioning

confidence: 99%

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

Tatokoro

Fujii²,

Kawakami

et al. 2010

Cancer Science

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We have recently reported favorable responses to a combination treatment comprising cimetidine, a cyclooxygenase-2 inhibitor and a renin-angiotensin-system inhibitor in metastatic renal cell carcinoma (RCC). In view of the potential synergistic effects of these three agents and interferon-a (I-CCA therapy), we conducted a phase-II trial to examine the efficacy and toxicity of I-CCA as firstline treatment. Fifty-one patients with advanced RCC received natural interferon-a (3-6 million U thrice/week) and cimetidine (800 mg), cyclooxygenase-2 inhibitor meloxicam (10 mg), and renin-angiotensin-system inhibitor candesartan (4 mg) or perindopril (4 mg) orally daily. Memorial Sloan-Kettering Cancer Center prognostic categories were favorable, intermediate and poor in 10 (20%), 31 (61%) and 10 (20%) patients, respectively. The primary end-point was the objective response rate (ORR) and the secondary end-points included clinical benefit, progression-free survival (PFS), overall survival (OS) and safety. Median follow-up was 19 months. Complete response (CR) was observed in four patients (8%) and partial response in seven (14%), yielding an ORR of 22%. None of the four patients who achieved CR relapsed during the 16-to 81-month follow up. The ORR were 17% in the favorable-or intermediate-risk group and 40% in the poor-risk group. The other 24 patients (45%) had stable disease for at least 6 months, resulting in a clinical benefit rate of 67%. The median PFS and OS were 12 and 30 months, respectively. Grade 3/4 toxicities were never observed. The I-CCA therapy, providing favorable responses and low toxicity profiles, is worthy of further consideration as a firstline therapy for metastatic RCC. (Cancer Sci 2011; 102: 137-143) R enal cell carcinoma (RCC) is the most common renal malignancy and accounts for approximately 2% of all cancers.(1) Metastatic disease is present in around 30% of RCC patients when diagnosed, and 30-40% of patients with earlystage disease relapse with metastases following nephrectomy. Renal cell carcinoma is highly resistant to conventional cytotoxic chemotherapy and the prognoses in patients with metastatic RCC (mRCC) are poor, (2) with a median overall survival (OS) period of approximately 1 year (3) and a 5-year survival rate of <10%. Immunoreactive cytokines, interferon-a (IFN-a) and interleukin-2 (IL-2) were the treatment mainstay for mRCC.(5) Interferon-a offers a small but significant advantage in OS. (6) However, cases of complete remission (CR) by IFN-a are rare and progression-free survival (PFS) is reported to be approximately 5 months. (7,8) High-dose immunotherapy with intravenous IL-2 results in generally durable CR in approximately 6% of patients, but significant toxicities can occur with this regimen, making it applicable to a limited number of patients. Based on a better understanding of the biology and genetics of RCC, targeted agents have been developed and shown to have significant antitumor activities against RCC, resulting in dramatic paradigm shifts in the management of mRCC....

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Section: (A) (B) (C) (D) (E) (F)mentioning

confidence: 99%

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

Tatokoro

Fujii²,

Kawakami

et al. 2010

Cancer Science

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“…A recent cohort study has also demonstrated a lower incidence of cancer in patients using ACE-I or an AT-II receptor blocker (ARB) than nonusers [40]. Furthermore, it has been reported that the addition of ACE-I or ARB provided the prolonged survival for the patients with advanced non-small cell lung cancer undergoing platinum-based chemotherapy [41]. Additionally, inhibition of RAAS possibly exerted the beneficial effects on the prognosis of patients with advanced hormone-refractory prostate cancer and pancreatic cancer receiving gemcitabine [42,43].…”

Section: Raas Blockersmentioning

confidence: 99%

Antiangiogenic Therapy for Hepatocellular Carcinoma

Kaji¹,

Yoshiji²

2017

Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

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Angiogenesis plays a pivotal role in many pathological processes, including hepatocellular carcinoma (HCC). This indicates that antiangiogenic agents could be promising candidates for chemoprevention against HCC. Several inhibitors targeting receptor tyrosine kinases (RTKs) for the regulation of tumoral vascularization have been developed and employed in clinical practice, including sorafenib. However, there seem to be several issues for the long-term use of this agent as some patients have experienced adverse effects while taking sorafenib. Therefore, it is desirable for patients with chronic liver diseases to be administered sorafenib as little as possible by combining other safe-to-use antiangiogenic compounds. Various factors, such as renin-angiotensin-aldosterone system (RAAS) and insulin resistance (IR), reciprocally contribute to the promotion of angiogenesis. A blockade of RAAS with an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin-II (AT-II) receptor blocker (ARB) markedly attenuates HCC in conjunction with the suppression of angiogenesis. Moreover, the IR status has demonstrated direct acceleration in the progression of HCC via the augmentation of tumoral neovascularization. These findings suggest that a combination therapy involving a lower dose of sorafenib with other clinically used agents [e.g., RAAS blockers, insulin sensitizer agents, and branched-chain amino acids (BCAA)] may reduce the adverse effects of sorafenib without attenuating the inhibitory effect against HCC in comparison to a high-dose administration.

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“…Direct ACE signaling has also been reported (76,77), although its involvement in angiogenesis has not been described. Currently, ACE inhibitors are receiving attention as potential additional therapy to standard chemotherapeutic regimen with the proposed mechanism being angiogenesis inhibition (102,148). However, the effect of ACE via AT 1 Rmediated angiogenesis is insufficient to account for the reported discrepancies on the role of ACE inhibitors in cancer.…”

Section: Renin Angiotensin System and Angiogenesismentioning

confidence: 99%

“…Clinically, a number of retrospective studies have shown that ACE inhibitor use is associated with reduced cancer risks (28,81,145). ACE inhibition in combination with other therapies have been found to improve outcome in certain tumors such as pancreatic (102) and nonsmall lung cancer (148), with AT 1 R-mediated regulation of downstream genes associated with angiogenesis being a proposed mechanism (64,139). However, there are also abundant studies that suggest neutral or even negative impact of ACE inhibitor or RAS blocker use on specific cancers in clinical models (6,132,153).…”

mentioning

confidence: 99%

Angiotensin-converting enzyme and the tumor microenvironment: mechanisms beyond angiogenesis

Okwan-Duodu

Landry

Shen

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Okwan-Duodu D, Landry J, Shen XZ, Diaz R. Angiotensin-converting enzyme and the tumor microenvironment: mechanisms beyond angiogenesis. Am J Physiol Regul Integr Comp Physiol 305: R205-R215, 2013. First published June 5, 2013 doi:10.1152/ajpregu.00544.2012.-The renin angiotensin system (RAS) is a network of enzymes and peptides that coalesce primarily on the angiotensin II type 1 receptor (AT 1R) to induce cell proliferation, angiogenesis, fibrosis, and blood pressure control. Angiotensin-converting enzyme (ACE), the key peptidase of the RAS, is promiscuous in that it cleaves other substrates such as substance P and bradykinin. Accumulating evidence implicates ACE in the pathophysiology of carcinogenesis. While the role of ACE and its peptide network in modulating angiogenesis via the AT 1R is well documented, its involvement in shaping other aspects of the tumor microenvironment remains largely unknown. Here, we review the role of ACE in modulating the immune compartment of the tumor microenvironment, which encompasses the immunosuppressive, cancer-promoting myeloidderived suppressor cells, alternatively activated tumor-associated macrophages, and T regulatory cells. We also discuss the potential roles of peptides that accumulate in the setting of chronic ACE inhibitor use, such as bradykinin, substance P, and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), and how they may undercut the gains of anti-angiogenesis from ACE inhibition. These emerging mechanisms may harmonize the often-conflicting results on the role of ACE inhibitors and ACE polymorphisms in various cancers and call for further investigations into the potential benefit of ACE inhibitors in some neoplasms.

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Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy

Abstract: Addition of ACEI or ARB to platinum-based first-line chemotherapy may contribute to prolonged survival in patients with advanced lung cancer.

Cited by 151 publications

References 34 publications

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

Antiangiogenic Therapy for Hepatocellular Carcinoma

Angiotensin-converting enzyme and the tumor microenvironment: mechanisms beyond angiogenesis

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