Statin Therapy Is Associated With Improved Pathologic Response to Neoadjuvant Chemoradiation in Rectal Cancer

Mace, Adam G.; Gantt, Gerald; Skacel, Marek; Pai, Rish K.; Hammel, Jeff; Kalady, Matthew F.

doi:10.1097/dcr.0b013e3182a4b236

Cited by 64 publications

(62 citation statements)

References 26 publications

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“…Numerous studies and meta-analysis have investigated whether statin use reduces the risk of developing CRC [14], [15]. Fewer studies focus on effects of statin after diagnosis during treatment [16]–[21]. The study of Mace et al [16] showed that rectal cancer patients in the statin cohort treated with neo-adjuvant chemoradiation had a better response (65.7% versus 48.7%, p = 0.004) and lower median regression rate (1 versus 2, p = 0.01).…”

Section: Discussionmentioning

confidence: 99%

“…Fewer studies focus on effects of statin after diagnosis during treatment [16]–[21]. The study of Mace et al [16] showed that rectal cancer patients in the statin cohort treated with neo-adjuvant chemoradiation had a better response (65.7% versus 48.7%, p = 0.004) and lower median regression rate (1 versus 2, p = 0.01). Two other studies [19], [20] in patients with rectal cancer treated with neo-adjuvant chemoradiation showed similar results indicating an association between statin use and response.…”

Section: Discussionmentioning

confidence: 99%

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Statin Use Is Not Associated with Improved Progression Free Survival in Cetuximab Treated KRAS Mutant Metastatic Colorectal Cancer Patients: Results from the CAIRO2 Study

et al. 2014

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Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC) treated with cetuximab. Treatment data were obtained from patients who were treated with capecitabine, oxaliplatin bevacizumab ± cetuximab in the phase III CAIRO2 study. A total of 529 patients were included in this study, of whom 78 patients were on statin therapy. In patients with a KRAS wild type tumor (n = 321) the median PFS was 10.3 vs. 11.4 months for non-users compared to statin users and in patients with a KRAS mutant tumor (n = 208) this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR) for PFS for statin users was 1.12 (95% confidence interval 0.78–1.61) and was not influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction. Statin use adjusted for covariates was not associated with increased PFS (HR = 1.01, 95% confidence interval 0.71–1.54). In patients with a KRAS wild type tumor the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence interval 1.06–2.22). However, statin use, adjusted for covariates was not associated with increased OS (HR = 1.41, 95% confidence interval 0.95–2.10). In conclusion, the use of statins at time of diagnosis was not associated with an improved PFS in KRAS mutant mCRC patients treated with chemotherapy and bevacizumab plus cetuximab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Statin Use Is Not Associated with Improved Progression Free Survival in Cetuximab Treated KRAS Mutant Metastatic Colorectal Cancer Patients: Results from the CAIRO2 Study

et al. 2014

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“…Furthermore, HMGCR may serve as a predictive marker of response to postoperative radiotherapy in ductal carcinoma in situ (dCIS) (83). A retrospective cohort study suggested an association between statin therapy and improvement in response of rectal cancer to neoadjuvant chemoradiation (84).…”

Section: Synergism Of Statins With Radiotherapy and Chemotherapymentioning

confidence: 99%

Statins are potential anticancerous agents (Review)

2015

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Abstract. Statins are inhibitors of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR), which is a rate-limiting enzyme in the mevalonate pathway. The pleiotropic effects of statins may be mediated by the inhibition of downstream products such as small GTP-binding proteins, Rho, Ras and Rac whose localization and function are dependent on isoprenylation. Preclinical studies of statins in different cancer cell lines and animal models showed antiproliferative, pro-apoptotic and anti-invasive effects. Notably, statins showed targeted action in cancerous cell lines compared to normal cells. Previous studies have also shown the synergistic effects of statins with chemotherapeutic agents and radiotherapy. This effect of statins was also observed in chemotherapeutic-resistant tumors. Statins were reported to sensitize the cells to radiation by arresting them in the late G1 phase of the cell cycle. Similarly, population-based studies also demonstrated a chemopreventive and survival benefit of statins in various types of cancers. However, this benefit has yet to be proven in clinical trials. The interindividual variation in response to statins may be contributed to many genetic and non-genetic factors, including single-nucleotide polymorphisms in HMGCR gene and the overexpression of heterogeneous nuclear ribonucleoprotein A1, which was reported to reduce HMGCR enzyme activity. However, more studies with large phase III randomized controlled trials in cancer patients should be conducted to establish the effect of statins in cancer prevention and treatment.

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“…Patients in the statin cohort showed a better response than those not taking a statin (65.7 vs. 48.7 %, p = 0.004). The authors suggested that statin therapy was associated with an improved response to neoadjuvant therapy in rectal cancer [48].…”

Section: Metabolic Biomarkers As Risk and Prognostic Factors In Crcmentioning

confidence: 99%

The Association Between Adiposity and Survival in Patients with Colorectal Cancer

Durko

Małecka‐Panas

2016

Curr Nutr Rep

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Multiple studies confirm the impact of obesity on high incidence of colorectal cancer (CRC). There is a common perception that adiposity and related metabolic dysfunctions result in worse prognosis and decreased survival among patients with a CRC diagnosis. Several epidemiologic studies confirm this observation, however the results are not always consistent, probably due to different techniques used for evaluating the degree of adiposity. Many authors suggest that the most adequate method for assessing this parameter is computer tomography of the abdomen which allows to precisely quantify the amount of adipose tissue. Excess adipose tissue is considered a metabolically active organ releasing numerous adipohormones and cytokines that stimulate chronic inflammation, insulin resistance and contribute to increased cell proliferation. However, adiposity biomarker expression are welldocumented risk factors for CRC development, little is known about their prognostic value in this disease.

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Statin Therapy Is Associated With Improved Pathologic Response to Neoadjuvant Chemoradiation in Rectal Cancer

Abstract: Statin therapy is associated with an improved response of rectal cancer to neoadjuvant chemoradiation. These data provide the foundation for a prospective clinical trial.

Cited by 64 publications

References 26 publications

Statin Use Is Not Associated with Improved Progression Free Survival in Cetuximab Treated KRAS Mutant Metastatic Colorectal Cancer Patients: Results from the CAIRO2 Study

Statin Use Is Not Associated with Improved Progression Free Survival in Cetuximab Treated KRAS Mutant Metastatic Colorectal Cancer Patients: Results from the CAIRO2 Study

Statins are potential anticancerous agents (Review)

The Association Between Adiposity and Survival in Patients with Colorectal Cancer

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