peripheral neuropathy is a common , but a debilitating adverse effect of several classes of chemotherapeutic agents including vinca alkaloids , taxanes , and antitubulins .
the incidence of chemotherapy - induced peripheral neuropathy ( cipn ) can vary from 3% to 7% with a single agent and rise up to 38% in patients who are on combination therapy .
the severity of neuropathy depends on the dose of the chemotherapeutic agent , duration of exposure , cumulative dose , concurrent use of other agents , and coexisting disease such as diabetes , vitamin b12 deficiency , or alcoholism .
cipn pain is not only debilitating , but also may be the reason for stopping a lifesaving curative chemotherapy .
dysregulation in the calcium homeostasis in the dorsal nerve root ganglion and dorsal spinal cord has been implicated in the causation of neuropathic pain .
neuromodulators such as gabapentin and pregabalin inhibit the 2- subunit of the calcium channel in the neuronal cells thus reducing the neuropathic pain . between the two ,
a 17-year - old boy diagnosed with early precursor t - cell , all and no other medical comorbidities completed his induction phase with vincristine , cytarabine , and cyclophosphamide in july 2015 . in the beginning of august 2015 , he was started on consolidation phase of chemotherapy with vincristine , daunorubicin , polyethylene glycol daunorubicin asparaginase , and prednisolone .
midway through the consolidation ( after 2 cycles ) phase , he developed tingling sensation in the plantar aspect and toes of his feet , which progressed to  pins and needles  sensation in 1 week .
the pediatric oncology team abandoned his chemotherapy due to intolerable pain and admitted him for debilitating neuropathy .
they started him on ultracet ( tramadol 37.5 mg + paracetamol 325 mg ) 4 times a day for pain .
the patient spent most time in bed and used a wheel chair to go to the toilet . on examination ,
he had developed grade iii neuropathy ( cancer therapy evaluation program , common terminology criteria for adverse events , version 3.0 ) .
he was started on tablet pregabalin 75 mg at night and escalated his dose every 3 day by 75 mg until pain was controlled .
the boy had good pain control ( edmonton symptom assessment scale - 1/10 ) on day 15 with no side effects .
he was able to walk to the bathroom without support and do his routine activities without any discomfort .
a 40-year - old lady who was diagnosed with primary peritoneal serous carcinoma and no other medical comorbidities was administered paclitaxel and carboplatin . while she was on chemotherapy , she developed mild burning sensation in the plantar aspects of forefoot and toes bilaterally .
the pain was aggravated by walking , standing , and local application of pressure on the forefoot and toes .
, she was found to have grade iii peripheral neuropathy ( nci - ctc version 3.0 ) .
she was started on tablet pregabalin 75 mg at night , and the dose of pregabalin was increased by 75 mg every 3 days until resolution of pain .
the patient responded to a dose of 375 mg of pregabalin without any of the known side effects of pregabalin ( including drowsiness or giddiness ) .
her neuropathy improved from grade iii to grade i. she was able to get back to doing her routine household work . in view of radiological progression of her disease
she , however , continues to have  walking on cotton - wool  sensation and occasional tingling sensation in her toes .
a 17-year - old boy diagnosed with early precursor t - cell , all and no other medical comorbidities completed his induction phase with vincristine , cytarabine , and cyclophosphamide in july 2015 . in the beginning of august 2015 , he was started on consolidation phase of chemotherapy with vincristine , daunorubicin , polyethylene glycol daunorubicin asparaginase , and prednisolone .
midway through the consolidation ( after 2 cycles ) phase , he developed tingling sensation in the plantar aspect and toes of his feet , which progressed to  pins and needles  sensation in 1 week .
the pediatric oncology team abandoned his chemotherapy due to intolerable pain and admitted him for debilitating neuropathy .
they started him on ultracet ( tramadol 37.5 mg + paracetamol 325 mg ) 4 times a day for pain .
the patient spent most time in bed and used a wheel chair to go to the toilet . on examination ,
he had developed grade iii neuropathy ( cancer therapy evaluation program , common terminology criteria for adverse events , version 3.0 ) .
he was started on tablet pregabalin 75 mg at night and escalated his dose every 3 day by 75 mg until pain was controlled .
the boy had good pain control ( edmonton symptom assessment scale - 1/10 ) on day 15 with no side effects .
he was able to walk to the bathroom without support and do his routine activities without any discomfort .
a 40-year - old lady who was diagnosed with primary peritoneal serous carcinoma and no other medical comorbidities was administered paclitaxel and carboplatin .
while she was on chemotherapy , she developed mild burning sensation in the plantar aspects of forefoot and toes bilaterally . within 1 month , this progressed to severe burning pain in the same regions .
the pain was aggravated by walking , standing , and local application of pressure on the forefoot and toes .
, she was found to have grade iii peripheral neuropathy ( nci - ctc version 3.0 ) .
she was started on tablet pregabalin 75 mg at night , and the dose of pregabalin was increased by 75 mg every 3 days until resolution of pain .
the patient responded to a dose of 375 mg of pregabalin without any of the known side effects of pregabalin ( including drowsiness or giddiness ) .
her neuropathy improved from grade iii to grade i. she was able to get back to doing her routine household work . in view of radiological progression of her disease ,
she , however , continues to have  walking on cotton - wool  sensation and occasional tingling sensation in her toes .
certain chemotherapeutic agents belonging to vinca alkaloids , taxanes , and antitubulins class produce adverse effects such as sensory and motor neuropathy , laryngeal neuropathy , and sensory ataxia , which can significantly affect patient 's quality of life .
multiple mechanisms have been hypothesized in the causation of cipn , which include myelinopathy , axonopathy , intraepidermal nerve fiber loss , and mitotoxicity .
cipn occurs in the  glove and stocking  distribution and occasionally perioral paresthesia is experienced with certain chemotherapeutic agents .
sensory symptoms that are commonly reported include paresthesia , dysesthesia , allodynia , hyperalgesia , hypoalgesia , or pain that is burning , shooting , or electric - shock - like .
painful symptoms may persist well - beyond discontinuation of treatment ( so called  coasting  ) , resulting in a condition as painful or more painful than the original cancer .
cipn pain among other sensory symptoms has presently no standard protocol and the current approach is to stop the chemotherapeutic agent until the neuropathy resolves , in some conditions abandon the chemotherapy regimen and use a lower dose or alternative chemotherapeutic agent .
multiple approaches have been discussed to either prevent or treat chemotherapy - induced neuropathic pain . in a study , calcium gluconate and magnesium sulfate ( ca / mg ) infusions , prior and after oxaliplatin treatment , seemed active against acute symptoms ; however , the trial had to be interrupted as there was lower tumor response rate in this group .
duloxetine and venlafaxine are known to significantly reduce pain and paresthesia , but other antidepressants such as amitriptyline and nortriptyline failed to show any effect .
antidepressant drugs can produce serious adverse effects which might limit the dose escalation , especially in elderly .
these drugs significantly interact with other drugs concomitantly administered in cancer treatment resulting in serious adverse reactions .
neuromodulators such as gabapentin and pregabalin are gamma - aminobutyric acid analogs , which interact with the 2- subunit of the voltage - gated calcium channels , found to be effective in neuropathic pain .
cancer chemotherapeutic agents cause increased expression of sodium channel , 2-1 subunit of the calcium channel ( also activated by opening of sodium channel and n - methyl - d - aspartate [ nmda ] receptor activation ) , and nmda receptors at the dorsal nerve root ganglion and dorsal horn cells .
activation of these receptors leads to influx of extracellular calcium and leakage of the mitochondrial calcium .
this rise in the intracytoplasmic calcium leads to neuronal cell death through generation of toxic oxygen radicals and triggering of apoptosis .
gabapentin and pregabalin reduce the calcium - dependent neurotransmitters in the neuronal membrane , thus inhibiting the neuronal excitability .
pregabalin , in contrast to gabapentin , has a higher bioavailability ( 90% vs. 3366% ) , rapid absorption ( peak : 1 h ) with plasma concentration increasing linearly with increasing dose , which justifies its equivalent efficacy at a lower dose and lower risk of adverse effect . also as pregabalin
is not known to have drug - drug interaction , it can be safely co - administered with chemotherapeutic agents .
our patients showed reduction in the hyperalgesia and allodynia and improvement in the quality of life .
the common side effects include dizziness and somnolence , which is known to resolve with continued treatment , followed by dry mouth , peripheral edema , blurred vision , weight gain , abnormal thinking , myoclonus , asterixis , and gynecomastia .
chemotherapy - induced neuropathic pain though an uncommon side effect has significant impact on the quality of life of the patients
. the current approach of reducing the dose of chemotherapy or stopping the medication can significantly affect the survival of the patients .
there is , thus , a need to explore the use of neuromodulators such as pregabalin in the management of chemotherapy - induced neuropathic pain .
 chemotherapeutic agents belonging to vinca alkaloids , taxanes , and antitubulins produce peripheral neuropathy for which there is no validated treatment . 
 pregabalin , a gamma - aminobutyric acid analog , is known to inhibit the2 subunit of the voltage - gated calcium channel . 
 earlier studies and case reports have shown pregabalin to be effective in treating neuropathic pain . 
 we present a case series of patients with chemotherapy - induced peripheral neuropathy who were successfully treated with pregabalin with reduction in the hyperalgesia , allodynia , and improvement in the quality of life . 
INTRODUCTION
CASE REPORTS
Case 1
Case 2
DISCUSSION
CONCLUSION
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