Table 3.
Clinical studies of statin use for patients with malignant tumors.
| Authors, Year | Study Type | Patients | Evaluation | Comparison | Outcome | Results |
|---|---|---|---|---|---|---|
| Garwood, 2010 [117] | II | High grade ER- negative breast cancer | High dose fluvastatin | Low dose fluvastatin | Ki-67 index, caspase 3 cleavage | Fluvastatin increases apoptosis and decreases proliferation of cancer cells. |
| Feldt, 2015 [118] | II | Invasive breast cancer | Atorvastatin | None | p27, cyclin D1 | Atorvastatin induces anti-proliferative effects through up-regulation of tumor suppressor p27 and down-regulation of cyclin D1. |
| Alarfi, 2020 [119] | II RCT | Metastatic breast cancer | Simvastatin, carboplatin, vinorelbine | Carboplatin, vinorelbine | ORR, OS | The chemo-sensitizing effect was investigated, but simvastatin did not improve ORR, and OS. |
| Yulian, 2021 [120] | II RCT | Advanced breast cancer | Simvastatin, FU, ADM, CPA | FU, ADM, CPA | ORR, OS | Simvastatin increased pathlogical ORR but did not improve OS. |
| Kornblau, 2007 [121] | I | New AML and recurrent AML | Pravastatin, idarubicin, cytarabine | Historical control | ORR | Pravastatin idarubicin, and high-dose cytarabine induce CR in 11 new patients and 9 salvage patients. |
| Advani, 2014 [122] | II | Relapsed AML | Pravastatin, idarubicin, cytarabine | Historical control | ORR | Idarubicin, cytarabine, and pravastatin improve the ORR. |
| Advani, 2018 [123] | II RCT |
New AML | Pravastatin, idarubicin, cytarabine | Idarubicin, cytarabine | ORR | Pravastatin did not meet the prespecified efficacy criteria in newly diagnosed 24 AML patients. |
| Schmidmaier, 2007 [124] | II | Multiple myeloma, treated with two cycles of bortezomib or bendamustine | Simvastatin plus additional 2 cycles of bortezomib or bendamustine | Additional 2 cycles of bortezomib or bendamustine | Chemotherapy resistance | Simvastatin reduces chemotherapy resistance in 6 patients with refractory MM compared to 10 patients treated with chemotherapy alone. |
| Hus, 2011 [125] | II RCT |
Relapsed or refractory multiple myeloma | Lovastatin, thalidomide, dexamethasone | Thalidomide, dexamethasone | OS, PFS | Lovastatin prolongs OS and PFS. |
| Alexandre, 2020 [126] | II RCT |
Esophageal cancer | Esophagectomy with simvastatin | Esophagectomy without simvastatin | OS, PFS | The one-year simvastatin administration for patients with esophageal cancer who had undergone esophagectomy did not conclude the survival outcomes. |
| Kim, 2001 [127] | II | Advanced gastric cancer | Lovastatin, ubiquinone | None | ORR, toxicity | Lovastatin with ubiquinone was ineffective. NO ORR improvement was observed. |
| Konings, 2010 [128] | II RCT |
Advanced gastric carcinoma | Pravastatin, epirubicin, cisplatin, capecitabine | Epirubicin, cisplatin, capecitabine | OS, PFS | Pravastatin did not improve OS and PFS. |
| Kim, 2014 [129] | III RCT |
Metastatic gastric or EC junction adenocarcinoma | Simvastatin, capecitabine, cisplatin | Capecitabine, cisplatin | PFS | Simvastatin did not increase PFS compared with chemotherapy alone. |
| Lim, 2015 [130] | III RCT |
Metastatic colorectal cancer | Simvastatin, FOLFIRI or XELIRI |
FOLFIRI or XELIRI | OS, PFS | Simvastatin plus chemotherapy did not increase OS and PFS compared with chemotherapy alone. |
| Jouve, 2019 [131] | RCT | Advanced hepatocellular carcinoma | Pravastatin, sorafenib | Sorafenib | OS, PFS, TTP | Sorafenib plus pravastatin did not improve TTP, PFS, and OS compared with sorafenib alone. |
| Blanc, 2021 [132] | II RCT |
Advanced hepatocellular carcinoma | Pravastatin, sorafenib | Sorafenib alone or pravastatin alone. | OS PFS | Sorafenib or pravastatin did not improve outcomes. Sorafenib is potentially effective. |
| Riano, 2020 [133] | II RCT |
Advanced hepatocellular carcinoma | Pravastatin, sorafenib | Sorafenib | OS, TTP | Sorafenib plus pravastatin did not improve TTP compared with sorafenib alone. |
| Kawata, 2001 [134] | RCT | Advanced hepatocellular carcinoma | Pravastatin, embolization, FU | Embolization, FU | OS | Transcatheter arterial embolization followed by fluorouracil and pravastatin prolongs OS compared with the standard therapy alone. |
| Hong, 2014 [135] | II RCT |
Advanced pancreatic cancer | Simvastatin, gemcitabine | Gemcitabine | TTP | Gemcitabine plus simvastatin did not decrease TTP compared with gemcitabine alone. |
| Seckl, 2017 [136] | III RCT |
Small cell lung cancer | Pravastatin, etoposide plus cisplatin or carboplatin | Etoposide plus cisplatin or carboplatin | OS, PFS | Pravastatin did not offer additional benefits. |
| Lee, 2017 [137] | II RCT |
Lung cancer (NSCLC, non- adenocarcinomas) | Simvastatin, afatinib | Afatinib | ORR | Simvastatin did not improve response rates. compared with afatinib alone in patients with non-adenocarcinomas |
| Han, 2011 [138] | II RCT |
Lung cancer (NSCLC) | Simvastatin, gefitinib | Gefitinib | PFS, ORR | No outcome improvement was observed. Simvastatin increases response rates and PFS only in patients with EGFR wild type non-adenocarcinoma. |
ADM, Adriamycin; AML, acute myeloid leukemia; CPA, cyclophosphamide; CR, complete remission; EC, esophageal-gastric; EGFR, epidermal growth factor receptor; ER, estrogen receptor; FOLFIRI, Leucovorin, 5-FU, and irinotecan; FU, fluorouracil; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression free survival; RCT, randomized clinical trial; TTP, time to progression; XELIRI, capecitabine and irinotecan; I, phase I; II, phase II; III, phase III.