A drug used to treat multiple sclerosis (MS) could help reduce neuropathic pain in cancer patients being treated with a chemotherapy drug, according to researchers at St. Louis University.
“The chemotherapy drug paclitaxel is widely used to treat many forms of cancer, including breast, ovarian and lung cancers,” said Daniela Salvemini, PhD, a professor of pharmacological and physiological sciences at St. Louis University.
“Though it is highly effective, the medication, like many other chemotherapy drugs, frequently is accompanied by a debilitating side effect called chemotherapy induced peripheral neuropathy, or CIPN.”
CIPN occurs in 30 to 90 percent of patients treated with paclitaxel, which is also known as the brand name Taxol. The chemotherapy induced neuropathy can appear as tingling or numbness in the hands and feet, a shooting or burning pain in the limbs, or it can feel like hot or cold temperature extremes.
The symptoms may resolve within weeks or months of stopping chemotherapy treatment or they may last for years. In addition to causing cancer patients additional suffering, CIPN can also discourage patients from getting further treatment.
In a study published study in the Journal of Biological Chemistry, Salvemini describes two discoveries: the molecular pathway by which CIPN develops and a drug that may be able to stop it.
Salvemini and her colleagues found that the pain pathway is dependent on activation of sphingosine 1-phosphate receptor subtype 1 (S1PR1) in the central nervous system, which triggers a series of damaging neuro-inflammatory processes leading to neuropathic pain. By inhibiting that process, they found that they could block and reverse paclitaxel-induced neuropathic pain without interfering with the drug’s anticancer effects.
A drug that modulates S1PR1 is already on the market. Fingolimod, which is sold by Novartis (NYSE: NVS) under the brand name Gilenya, was approved by the FDA in 2010 to treat MS, a chronic disease which attacks the body’s central nervous system and destroys the myelin sheath that protects nerve cells.
Like many MS drugs, Gilenya is expensive, costing about $48,000 a year. Over 91,000 MS patients have been treated with Gilenya, generating sales of over $2 billion last year.
When Salvemini tested Gilenya in her lab, she found that the S1PR1 modulator weakened the neuroinflammatory process, which blocked and reversed neuropathic pain without altering the anticancer properties of paclitaxel. The beneficial effects of Gilenya were not restricted to paclitaxel, but also extended to another chemotherapy drug, the platinum based drug oxaliplatin, which is widely used for metastatic colon cancer and other gastrointestinal cancers.
While clinical trials will be necessary to determine the safety and efficacy of Gilenya in treating CIPN, researchers are hopeful it may be able not only relieve cancer patients of CIPN, but also save more lives by permitting the administration of larger and potentially more effective doses of chemotherapy drugs.
“We have identified a critical pathway by which CIPN develops and continues that can be targeted with a drug that is already FDA approved. This does not happen often,” said Salvemini. “We need to capitalize on these findings and explore use of these agents in cancer pain patients to improve quality of life and potentially maximize anticancer efficacy as soon as possible.”
This study was funded by the Leukemia and Lymphoma Society Translational Research Program and the Mayday Fund with additional support from the Saint Louis University Cancer Center.