Ovarian cancer mortality rates have dropped by 16 % in the US and 10% in the EU over the last 10 years. Some attribute this to changes in oral contraceptive use and menopausal hormone replacement therapy. Improvements in diagnosis and treatment also contribute to this improvement in the high income populations. Even so, almost 75 % of women are diagnosed in Stage 3 or 4. 5-year survival is around 45-50 %. Standard treatment is currently initial surgery to reduce tumor burden (cytoreductive surgery) followed by chemotherapy OR initial chemotherapy to reduce tumor burden followed by surgery. If the disease responds to this initial treatment, it runs a high risk of relapsing. Early relapses signify chemotherapy resistance, with lower expectations of responses to 2nd and 3rd line treatments.

 How can we improve results now, while we wait for better treatments?

There are a number of interventions, which have shown benefit in improving responses and overall survival, and decreasing development of resistance to first line chemotherapy, with little risk of additional side effects. There is adequate epidemiological and phase 2 trial data for oncologists and patients to strongly consider adding these interventions to their current treatment plan.

 What interventions can you consider?

Metformin is an oral diabetes drug, which has also been shown to restrict ovarian cancer stem cell growth. Diabetic patients with ovarian cancer on metformin had fewer relapses, better able to complete cytoreductive surgery, and had better 5-year survival than those were not diabetic, or were not on metformin. An NCI sponsored phase 3 trial is underway, but results will not be available for many more years. If enrolling in the trial is not possible, (ClinicalTrials.gov Identifier: NCT01579812), consider using metformin off trial.

 Beta-blockers are oral medicines that are commonly used to treat high blood pressure, angina, heart failure and chronic migraines. These work by blocking the beta-adrenergic receptor that is activated in the stress response. Studies have shown that a chronically activated stress response helps the survival of ovarian cancer cells, and using beta-blockers decreases that effect. An NIH funded retrospective analysis has shown increased survival in patients who had been on Propranolol than not.

 Vitamin D has been shown to decrease proliferation, invasiveness and metastatic potential of cancer cells in laboratory studies. It is not present in most food groups. It is produced in the skin and activated in the liver and kidney. Deficiency is common in the older age group, and in populations with low sun exposure. Higher levels of Vitamin D have been associated with longer survival in a study published by the Australian Ovarian Cancer Study Group. Ensure that your Vitamin D dose is adequate for you.

 Itraconazole is a commonly used anti fungal medication. In the laboratory, it has also been shown to decrease blood vessel formation and oxygen supply to tumors.  It helps to overcome multidrug resistance in ovarian cancer relapses, increasing survival. In lung cancer, it has added survival benefit to currently used chemotherapy.

 Statins are commonly used cholesterol lowering medications. In the laboratory, they show interference in cancer cell biology. A review of patients who were on statin therapy at the time of their ovarian cancer had longer survival than those who were not.

 All these treatments need further clinical trials. However conducting randomized trials in this group of generic drugs is challenging due to limited available funding.  In the absence of large scale trials, available data may be sufficient for clinicians and patients to consider these interventions. If you would like to support further study of such interventions which show great promise at low cost, do visit www.global-cures.org. Full disclosure: I am on their scientific advisory committee. They are dedicated to the mission of improving cancer treatment outcomes with existing low cost measures.

 References:

1) https://annonc.oxfordjournals.org/content/early/2016/09/02/annonc.mdw306.full

 2)http://jco.ascopubs.org/content/34/28/3460.full

 3)Gynecol Oncol. 2008 Oct;111(1):102-5.

 4)ANTICANCER RESEARCH 34: 2481