A Descriptive Study on Pain Relief by Gabapentin or Pregabalin in the Patients of Chemotherapy Induced Peripheral Neuropathy in the Outpatient Department of Radiation Oncology, SMS Hospital, Jaipur (Rajasthan)

Cancer is currently a leading cause of mortality worldwide. However, due to advances in medicine

and modern technology, the availability of sensitive tests and diagnostic methods to detect cancer at

an early stage and the use of increasingly effective treatments, including chemotherapeutic agents,

the number of cancer survivors is rising. Although these survivors may have beaten cancer, many of

them have poor outcomes due to a number of syndromes that reduce the quality of life as a

consequence of cancer treatment, including pain, which they often experience for a long time after

completing their cancer treatment.

Chemotherapy is a well-known and effective treatment for different cancers. Cancer chemotherapy

refers to the administration of cytotoxic chemicals, i.e. chemicals with cell killing properties, with

the aim to, in some cases, eradicate the tumour or, at least, reduce the tumour burden and, thereby,

reduce the tumour-related symptoms and perhaps prolong life. Cytotoxic drugs are mostly given in

specific combinations of two or more drugs with the aim to increase the possibility to overcome

tumour cell resistance, procure the activity of the regimen against different tumour cell clones and

to avoid pronounced toxicity from normal tissues.

Chemotherapy Induced Peripheral Neuropathy (CIPN) is a common and challenging complication

of several frequently administered antineoplastic agents. The development of CIPN may result in

prolonged infusion times, dose reduction or premature cessation of chemotherapy, which may

negatively impact both treatment efficacy and patient survival .

Chemotherapy Induced Peripheral Neuropathy (CIPN) is a debilitating and dose-limiting side effect

manifested mainly by a sensory, length-dependent process, that results from a drug cumulative

dose. CIPN symptoms can be sufficiently severe to require a reduction in drug dosage or

discontinuation of treatment, causing a significant hindrance to favorable outcomes and

long-term patient quality of life.

CIPN is associated with many drugs that differ both in their antineoplastic action and in the

proposed neurotoxic mechanism. CIPN has been reported in patients treated with platinum-based

drugs, including cisplatin and oxaliplatin, microtubule-targeting agents (MTA) such as taxanes

(paclitaxel and docetaxel), vinca alkaloids (particularly vincristine and vinblastine), epothilones and

eribulin, and also proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide).

Although the specific anticancer effect of all classes of drugs is well known, their molecular and

cellular impact on the peripheral nervous system is not completely clear. While some classes ofantineoplastic drugs have potentially the antiproliferative mechanism strictly linked to their

neurotoxicity action (i.e., anti-tubulin compounds), others, for example, the platinum-based drugs,

show different neurotoxic effects unrelated to their antineoplastic activity.

Whilst in many cases, acute CIPN will resolve after finishing chemotherapy, in a number of cases,

it will persist, resulting in chronic symptoms, months, or even years later.

In some cases, CIPN can emerge shortly after finishing chemotherapy, a phenomenon known as

“Coasting”

Gabapentin and Pregabalin are often considered first-line treatment for various neuropathic pain

syndromes, generally irrespective of cause. Gabapentin and pregabalin are Anti-Seizure Drugs

(ASDs) that consist of a GABA (Gamma-Aminobutyric Acid) molecule covalently bound to either

a lipophilic cyclohexane ring or isobutane. Gabapentin was designed to be a centrally active GABA

agonist, with its high lipid solubility aimed at facilitating its transfer across the blood-brain barrier.

Gabapentin and Pregabalin, anticonvulsant analogs of GABA that are effective treatments for

neuropathic (nerve injury) pain act at the α2δ1 subunit of voltage-gated calcium channels.

N-methyl-D-aspartate (NMDA) receptors appear to play a very important role in central

sensitization at both spinal and supraspinal levels.

Gabapentin and Pregabalin bind to the alpha-2 (α-2δ) subunit of voltage-gated calcium channels in

the CNS, subsequently inhibiting the release of excitatory neurotransmitters. Its oral bioavailability

is ≥90% and can be taken with or without food. These drugs do not bind to plasma proteins,

undergo negligible metabolism, and do not affect the major CYP450 enzymes in humans. It is

unlikely to have significant drug interactions.

Gabapentin and Pregabalin are absorbed after oral administration and are not metabolized in

humans. These drugs are not bound to plasma proteins and are excreted unchanged, mainly in the

urine. Their half lives, when used as monotherapy, approximately 6 hrs.

Both Gabapentin and Pregabalin are well tolerated. Dizziness and somnolence are the most

common side effects in both drugs (>20% seen in gabapentin).[8] Confusion and peripheral edema

have also been reported with gabapentin.

With both drugs, side effects are dose dependent and reversible if the medication is discontinued.

The abrupt discontinuation of any form of gabapentin is not recommended because withdrawal

symptoms such as anxiety, insomnia, nausea, pain, and sweating may present.