Neurologic Complications of Platinum-based Chemotherapy

Introduction

Palliative, adjuvant, and neoadjuvant chemotherapy are the different types of anti-cancer chemotherapy. Chemotherapy helps in reducing the tumor bulk. Tumors are a group of abnormal growing cell mass in the body. Chemotherapy treats lung, ovary, breast, testicular, head, and neck cancer. The focus of chemotherapy is to achieve disease-free conditions and improve survival. Cisplatin, Carboplatin, and Oxaliplatin are platinum-based chemotherapeutic drugs used to treat metastatic (a condition in which tumors invade other body organs) cancer. Platinum-based chemotherapies adversely affect the nervous system (brain and spinal cord). The neurotoxicity induced by platinum-based chemotherapies is most commonly observed in patients who received high doses of Cisplatin. Neurotoxicity means toxicity to the nervous system caused by the side effects of cis-platinum-based chemotherapy in patients with cancer. Neurological complications of chemotherapy compromise the quality of life in cancer patients. The side effects of chemotherapy inhibit treatment. The symptoms of neurotoxicity can appear during chemotherapy or after some time when chemotherapy is discontinued. Encephalopathy and peripheral neuropathy are common neurological complications of platinum-based chemotherapy.

What Is Platinum-Based Chemotherapy?

Chemotherapy is anti-cancer therapy given to cancer patients. The goal of treatment is to cure cancer. Chemotherapy is the most common treatment and is primarily used to treat patients with metastatic disease. These Platinum-based drugs are used in chemotherapy to treat patients with cancer. These drugs treat lung, ovary, breast, testicular, head, and neck cancer. Platinum-based chemotherapy includes Cisplatin, Carboplatin, and Oxaliplatin. The most effective platinum-based drug is Cisplatin, and it is widely used. But these platinum-based chemotherapies have adverse effects also. The goal of chemotherapy is to improve symptoms and quality of life. The increment in lifespan is secondary. The treatment aims to ensure that patients tolerate chemotherapy well. Palliative care focuses on minimizing the adverse effects of chemotherapy.

What Are the Side Effects of Platinum-Based Chemotherapy?

The platinum-based chemotherapy has some common side effects, such as:

• Peripheral Neuropathy - A disease in which neurons in the limbs become damaged, causing immobility and weakness of limbs. Peripheral neuropathy results from axonal degeneration or demyelination (a condition in which the protective sheath of a neuron gets damaged) of the nerves.

• Encephalopathy - The condition which affects brain structure and function, causing brain dysfunction resulting in altered mental state and confusion. Encephalopathy is caused by the degeneration of brain cells.

• Lhermitte’s Sign - The condition in which an electric shock-like sensation is felt while flexing the neck, and it travels from the neck to the spine.

• Optic Neuritis - The condition in which the inflammation of the optic nerve occurs, causing blindness. Optic Nerve is the bundle of nerves that carry visual information from the eye to the brain.

• Autonomic Neuropathy - The condition in which the nerve damage that controls the autonomic function of the body, like blood pressure, temperature balance, digestion, and sexual functions. Autonomic neuropathy is characterized by difficulty in digestion, altered sexual function, dizziness, urinary problem, confusion, and altered mental state.

• Ototoxicity - The condition in which the inner ear is damaged, resulting in loss of hearing.

• Retinopathy - The condition in which retina gets damaged, resulting in blurred vision, episodic visual loss, and impaired color vision. If retinopathy is left untreated, it can cause color blindness.

What Are the Symptoms of Neurotoxicity?

• Patients experience a tingling and painful sensation in their limbs (paraesthesia).

• Patients are unable to move their ankles.

• Pain in the limbs.

• Numbness.

• Muscle cramps.

• Weakness.

• Loss of mobility due to paraesthesia in the limbs.

• Loss of proprioception (awareness).

• Electric-shock sensation experienced by patients on bending the neck.

• Hearing loss (ototoxicity).

• Vertigo (dizziness).

• Ataxia (impaired coordination).

• Retinopathy (an eye disorder resulting in vision loss).

• Loss of vision.

• Seizures.

• Brain dysfunction.

• Hallucination.

• Headache.

• Lethargy.

What Are the Neurologic Complications of Platinum-Based Chemotherapy?

Neurotoxicity is a common problem that occurs during or after chemotherapy in cancer patients. Peripheral neuropathy is a neurological complication that occurs after cis-platinum chemotherapy. Neurotoxicity means toxicity to the nervous system caused by the side effects of cis-platinum-based chemotherapy in patients with cancer. Platinium-based agents such as Cisplatin used in chemotherapy for cancer patients are more toxic to the nervous system. In addition, the cumulative dose can cause neuropathy. Studies have shown that patients receiving doses higher than 400 mg/m2 of Cisplatin show the onset of neuropathy symptoms. The neuropathy symptoms are also seen in patients receiving a dose of 200mg/m2 Cisplatin, as some patients are more susceptible. Neuropathy symptoms are seen after the termination of Cisplatin or during chemotherapy.

The following are the neurological complication of platinum-based chemotherapy:

• Peripheral Neuropathy - Peripheral neuropathy results from axonal degeneration or demyelination of the nerves. Cisplatin affects the brain and nervous system and causes apoptosis (programmed cell death) of brain cells. The symptoms of neurotoxicity can worsen and extend from distal parts of the body to proximal parts. The high dose of carboplatin can also cause severe sensory neuropathy. Similar to Cisplatin, Oxaliplatin is also dose-limiting and causes neuropathy. The prognosis differs from Cisplatin in the case of Oxaliplatin symptoms of neuropathy resolves after cessation of Oxaliplatin.

• Ototoxicity - Ototoxicity is the second most common neurotoxicity after peripheral neuropathy. Ototoxicity is a loss of hearing, generally seen in patients who receive a high dose of Cisplatin. Ototoxicity is often associated with tinnitus (a condition in which a person feels a ringing sound in their ears). Symptomatic hearing loss can be resolved after cessation of chemotherapy.

• Vestibulopathy - Vestibulopathy is an uncommon complication of Cisplatin. Vestibulopathy is the condition in which inner ear damage, internal ear controls the balancing portion. Vestibulopathy is characterized by hearing loss, vertigo (dizziness), and ataxia (impaired coordination).

• Retinopathy - The condition in which the retina (a part of the eye) is damaged, causing vision loss. Retinopathy is a rare event that occurs with Cisplatin.

• Encephalopathy - The condition in which brain cells are damaged, causing brain dysfunction, is called encephalopathy. Encephalopathy rarely occurs with Cisplatin therapy. It is characterized by impairment of body balance and blindness.

• Stroke - High dose of Cisplatin can cause ischemic stroke. Ischemic stroke is a condition that occurs due to insufficient blood supply in the brain. Brain stroke means the death of brain cells, eventually leading patients to the coma.

How are Neurologic Complications of Platinum-Based Chemotherapy Treated?

The neuropathy induced by chemotherapy can be prevented by regular examination of cancer patients during or after chemotherapy. The first step for treatment is the discontinuation of potential drugs causing neurotoxicity. Symptomatic treatment and palliative care can help treat neurotoxicity.

The following are used in the treatment for neuropathy induced by chemotherapy:

• Amifostine.

• Glutamine.

• Vitamin E supplementation, as it reduces the risk of ototoxicity.

• Adrenocorticotro hormone (ACTH).

• Thiamine or Methylene blue can treat encephalopathy.

Conclusion

Encephalopathy and peripheral neuropathy are common neurological complications of platinum-based chemotherapy. In addition, prevention of side effects of chemotherapy can be possible with pretreatment screening during treatment. Careful follow-up aids prevention of neurological toxicity. The history of neuropathy shows improvement and complete recovery in patients. The patient should be re-evaluated before exposure to chemotherapy. However, emerging newer therapies gives good opportunity to cancer survival patients for delayed vulnerability to neurotoxicity resulting in prolonged life span.