Table 3 Clinical trial data on ARB use and cancer. Three primary studies designed to evaluate ARB use in cancer therapy showed mildly positive results.
From: Unlocking the potential of targeting the angiotensin II type 1 receptor in cancer
Study Name & Reference | Cancer Type | Phase & Design | ARB Intervention | Key Outcomes |
|---|---|---|---|---|
Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA) NCT01434134 | Breast (Early invasive scheduled for anthracyclines treatment) | Phase II | Candesartan 32 mg | Candesartan group shown significantly less decline in left ventricular ejection fraction [104] |
Prevention of Cardiac Dysfunction During Breast Cancer Therapy (PRADAII) NCT03760588 | Breast (Early invasive scheduled for anthracyclines treatment) | Phase II | Sacubitril/valsartan (97/103 mg) | Anthracycline-based treatment for early breast cancer is associated with a reduction in left ventricular ejection fraction that was not significantly attenuated by sacubitril-valsartan. [107] |
Evaluating the Effect of Candesartan vs Placebo in Prevention of Trastuzumab-associated Cardiotoxicity NCT00459771 | Breast (HER2 + ) | Phase III, RCT | Candesartan 32 mg/day during and post-trastuzumab | No significant benefit from the use of candesartan [106] |
A phase 1 study of combination therapy with gemcitabine and candesartan in patients with pancreatic cancer (GECA-1) UMIN000002152 | Pancreatic (unresecatble or recurrent) | Phase I, single arm open label | Candesartan 4 mg, 8 mg, 16 mg or 32 mg | Dose-limiting toxicity seen in 32 mg patients, with one patient at 16 mg showing grade 4 neutropenia [120] |
A phase 2 study of combination therapy with gemcitabine and candesartan in patients with advanced or recurrent pancreatic cancer (GECA-2) UMIN000005580 | Pancreatic (Advanced) | Phase II, Dose-escalation | Candesartan 8 mg or 16 mg + Gemcitabine | Improved progression-free survival with 16 mg dose (4.6 vs. 3.5 months, 16 vs 8 mg, respectively), 2/35 patients discontinued candesartan due to hypotension, PR in 11.4%, SD in 51.4% [108] |
Proton w/ FOLFIRINOX-Losartan for Pancreatic Cancer NCT01821729 | Pancreatic (Locally Advanced unresectable) | Phase II, Single arm | Losartan + FOLFIRINOX + chemoradiotherapy (proton) | Downstaging of locally advanced disease. Achieved complete surgical resection of 61% in locally advanced cases [109] |
Losartan and Nivolumab in Combination with FOLFIRINOX and SBRT in Localized Pancreatic Cancer NCT03563248 | Pancreatic (Locally advanced, borderline resectable) | Phase II, RCT | Losartan + FOLFIRINOX + SBRT + Nivolumab | No observed effect of losartan or losartan + nivolumab on R0 resection rate, PFS, OS or partial clinical response [110] |
Losartan and Hypofractionated Rx After Chemo for Tx of Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer (SHAPER) NCT04106856 | Pancreatic (Borderline resectable, locally advanced unresectable) | Phase I, Single arm | Losartan + Hypofractionated radiation therapy | Est. study completion: 2026-08-08 Aims to assess safety of losartan in combination with Hypofractionated radiation therapy, as well as hypotensive adverse events and patient reported QoL |
Imaging Perfusion Restrictions from Extracellular Solid Stress - An Open-label Losartan Study (ImPRESS) NCT03951142 | Brain (Primary and metastatic) | Phase II, Open label | Losartan | Delayed, Est. study completion: 2024-12-31 Aims to assess the impact of losartan on cerebral blood flow and solid stress as well as immunotherapy and/or radiotherapy |
Losartan + Sunitinib in Treatment of Osteosarcoma NCT03900793 | Osteosarcoma (Relapsed, refractory) | Phase I/Ib, Open label dose escalation | Losartan <50 mg up to <150 mg + Sunitinib | Est. study completion: 2027-02 Aims to assess dose-limiting toxicities of combination therapy, maximally tolerated dose and recommended phase 2 dose Secondary outcomes of anti-tumour activity |
Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy for the Treatment of Patients with Locally Recurrent, Refractory or Oligometastatic Head and Neck Squamous Cell Carcinoma NCT06211335 | Head and neck squamous cell carcinoma (Recurrent, refractory or oligometastatic) | Phase I/Ib Single arm open label | Losartan + Pembrolizumab + SBRT | Est. study completion: 2027-06 Aims to assess incidence of TRAE, with secondary outcomes of ORR, DOR, OS, and PFS |
PHL Treatment in Pancreatic Cancer NCT05365893 | Pancreatic (resectable, non-metastatic, post-NAT, pre-surgery) | Phase I, parallel assignment | Losartan 50 mg/day + Paricalcitol + Hydroxychloriquine | Estimated study completion: 2026-12-31 Aims to assess incidence of TRAE and compare biological effect of PHL treatment in PDAC |
