How Gel Form of Tamoxifen May Reduce Side Effects for Patients

According to new research, tamoxifen, the familiar therapeutic and preventive breast cancer drug, can be applied topically as a gel. The gel form reduces growth of cancer cells to the same degree as the traditional oral formulation of the drug, but with fewer troublesome side effects, researchers published in July in Clinical Cancer Research.

Tamoxifen is used to treat early breast cancer in women who have already been treated with surgery, radiation, and/or chemotherapy, working by blocking the activity of estrogen in the breast. This may stop the growth of some breast tumors that need estrogen to grow, according to Medline Plus.

It is usually prescribed in tablet form to be taken once or twice daily, and patients have reported side effects like increased bone or tumor pain, pain or reddening around the tumor site, hot flashes, nausea, excessive tiredness, depression, headache and thinning of hair.

“The most common nuisance side effect is hot flashes,” said lead author Seema Khan, M.D., a Northwestern Medicine surgical oncologist. “Some women also complain of weight gain, although it is not clear that this is really linked to tamoxifen use.”

Rarer, more serious side effects include a small increase in the risk of uterine cancer and risk of blood clots, but there side effects are not seen in women under 50, Khan told Good Days from CDF.

For the new study, Khan and her team at Northwestern University divided 27 pre- and post-menopausal women with non-invasive cancer ductal carcinoma in situ (DCIS) into two groups. Half received 4 mg/day tamoxifen in gel form or 20 mg/day oral tamoxifen for 6 to 10 weeks before breast-saving surgery.

After six to 10 weeks of applying the gel to the tumor site on the breast, a marker for cancer cell growth, Ki-67, in breast tissue had reduced a similar amount in the oral and topical tamoxifen groups. The scientists also found equal concentrations of tamoxifen present in the breast tissue of patients who used the gel and took the oral drug, but the blood levels of the drug were more than five times lower in those who used the gel.

“The drug concentrations in the blood are a lot lower with topical delivery, and so we anticipate that with very little drug in the circulation, the effects on the brain (hot flashes) and the uterus would be less,” Khan said.

Along with a lower concentration of tamoxifen in the blood, there was a reduction in proteins that cause blood clots, the researchers found. Hot flashes were equaly common in both groups.

“When the drug does not pass through the liver, as it does with pill use, the clotting effects are not seen,” Khan said.

The tamoxifen gel is no longer being manufactured, but they are in discussion to try to restart the process. It will likely be several years before the gel is available for clinical use, Khan said.

“Since it is not available yet, this is not practically useful at the moment, but something to keep an eye out for,” she said. “We are trying hard to develop other options for topical therapy for breast cancer prevention and DCIS.”