Taxane and
platinum drugs are important agents in the treatment of
cancer and have shown activity against a variety of
tumors, including ovarian, breast, and
lung cancer, either as single agents or in combination with other
chemotherapy drugs. However, a serious and prevalent side effect of
taxane (
docetaxel and all formulations/derivatives of
paclitaxel) and
platinum (
cisplatin,
carboplatin, and
oxaliplatin) agents is dose-limiting
chemotherapy-induced
peripheral neuropathy (CIPN). CIPN can result in
treatment delays, dose modifications, and, in severe cases, discontinuation of
chemotherapy. Consequently, effective treatments for CIPN are needed.
Dimesna (
BNP7787;
Tavocept; disodium 2,2'-dithio-bis-ethanesulfonate) is an
investigational drug that is undergoing international clinical development as a treatment that is coadministered with first-line
taxane and
platinum combination chemotherapy in patients with inoperable advanced primary
adenocarcinoma of the lung.
BNP7787 is currently being developed with the objective of increasing the survival of
cancer patients receiving
taxane- and/or
cisplatin-based
chemotherapy. Additional data indicate that
BNP7787 may also protect against common and serious
chemotherapy-induced toxicities, including
chemotherapy-induced
anemia,
nausea,
emesis, nephrotoxicity, and neuropathy, without interfering with antitumor activity of the chemotherapeutic agent(s). Studies herein show that
BNP7787 prevents aberrant microtubule
protein (MTP) polymerization that is caused by exposure of MTP to
paclitaxel or
cisplatin.
BNP7787 modulates
paclitaxel-induced hyperpolymerization of MTP in a dose-dependent manner, and
mesna, an in vivo metabolite of
BNP7787, protects against time-dependent
cisplatin-induced inactivation of MTP. We propose that interactions between
BNP7787 and MTP may play a role in BNP7787-mediated protection against CIPN.