Delayed Seizure Associated with Paclitaxel‐Cremophor EL in a Patient with Early‐Stage Breast Cancer

Abstract

Paclitaxel, a microtubule stabilizer, is an effective agent for treating cancer of the breast, ovary, head and neck, and lung. Because paclitaxel is insoluble in water, it is formulated with the micelle-forming Cremophor EL. Neurologic toxicity is well described with both the drug and this carrier, with most toxicities manifesting as peripheral neuropathy, motor neuropathy, autonomic neuropathy, and myopathy. Toxic effects on the central nervous system, such as seizures or encephalopathy, have been rarely reported; however, the seizures reported were closely related to the time of infusion. We describe a 41-year-old woman with no history of seizures who was treated with paclitaxel for breast cancer. Four days after the drug was infused, she developed a generalized tonic-clonic seizure that could not be attributed to other causes. The patient was treated with phenytoin and was able to complete her adjuvant chemotherapy with nab-paclitaxel without further events. Her condition was neurologically stable without phenytoin for the next 6 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible association (score of 3) between the delayed seizure and paclitaxel or its solvent, Cremophor EL. Clinicians should be aware of the potential for seizure activity in patients who receive paclitaxel formulated with Cremophor EL.

The Natural Product NI-07, Is Effective Against Breast Cancer Cells While Showing No Cytotoxicity to Normal Cells

“…Many of these drugs are delivered as cocktails [5,10]. While newer, water-soluble compounds are being developed for their potential anti-breast cancer efficacy [11][12][13][14][15], delivery and specificity remain major obstacles [16]. In all cases, side effects can be devastating and during treatment, the patient's quality of life is poor.…”

Epilepsy in women with gynecologic malignancies

“…Tracey et al [69] reported on one patient who was treated by paclitaxel formulated using Cremophor EL and who then developed delayed onset of seizures 4 days after drug infusion. There was no history of seizures, and no metabolic lesion was present.…”

“…There was no history of seizures, and no metabolic lesion was present. These researchers believed that the seizures were caused by paclitaxel or its carrier [69]. Because paclitaxel is insoluble in water, it is formulated with the micelle-forming Cremophor EL.…”

“…Each milliliter of sterile nonpyrogenic solution contains 6 mg paclitaxel, 527 mg of purified Cremophor EL (polyoxyethylated castor oil) and 49.7% (v/v) dehydrated alcohol. Cremophor EL is considered to be a neurotoxicity agent and its half-life at doses of 70-110 mg/m 2 ranges from 70 to 77 h. Thus, the carrier may have caused delayed seizures, and it is difficult to discriminate whether Cremophor EL and paclitaxel causes CNS side effects [69].…”

Modulation of Voltage-Gated Ion Channels on SH-SY5Y Neuroblastoma by Non-ionic Surfactant, Cremophor EL

“…CrEL is considered to be mainly responsible for peripheral neuropathy, which elicits the sensory symptoms (numbness, tingling, and burning pain) associated with the administration of formulation agents, [1][2][3][4] as well as for central neuropathy causing seizures. 5,6) One mechanism exerting the neurotoxicity of CrEL is thought to be based on disturbances in the microtubules in neurons. 7) Rat dorsal root ganglia (DRG) neurons and mouse neuroblastoma cells exposed in vitro to CrEL showed axonal degeneration and demyelination.…”