Common Cancer Drug More Detrimental than Beneficial at Low Dosage
A new study involving the most commonly used chemotherapeutic agent in breast cancer treatment revealed that low dosage of Paclitaxel may promote the metastasis of breast cancer cells to the liver.
"Paclitaxel and its analogous compounds are the first line agents widely used in clinical cancer chemotherapy. However, potential risks and reasonable treatment strategies of paclitaxel continue to be widely investigated," the researchers noted in a statement.
Paclitaxel is a drug used to treat ovarian, lung, breast, pancreatic and other types of cancer. It is listed in the World Health Organization's List of Essential Medicine.
The study, published in the FEBS Journal, clearly suggests that lowering the dosage of Paclitaxel to reduce the drug's toxic side-effect might do more harm than benefit.
Some of the major side effects of the drug include hair loss, muscle and joint pain and diarrhea. However, there have been reported cases of Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria during the clinical trial.
For the study, researchers conducted an investigation in the gene expression patterns in invasive breast cancer cells treated with low or clinically relevant high doses of paclitaxel using microarray analysis. Potential effects of low doses of paclitaxel on cell migration, invasion and metastasis were also investigated in vivo and in vitro.
Their analysis revealed that low dosage of paclitaxel promoted inflammation and initiated the epithelial-mesenchymal transition that enhanced the migration of tumor cells and invasion in vitro. Additionally, low doses of the chemotherapeutic agent promoted liver metastasis in mouse xenografts, which correlated with changes in estrogen metabolism in the host liver.
"Collectively, these findings reveal the paradoxical and dose-dependent effects of paclitaxel on breast cancer cell activity, and suggest that increased consideration be given to potential adverse effects associated with low concentrations of paclitaxel during treatment," the author wrote on their study.