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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 11  |  Issue : 1  |  Page : 17-20

Occurrence of chemotherapy-induced peripheral neuropathy in cancer patients at Belagavi city: An observational study


Department of Neurophysiotherapy, KLEU Institute of Physiotherapy, Belagavi, Karnataka, India

Date of Submission23-Dec-2016
Date of Acceptance16-May-2017
Date of Web Publication18-Aug-2017

Correspondence Address:
Jorida Fernandes
KLEU Institute of Physiotherapy, Belagavi - 590 001, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/PJIAP.PJIAP_1_16

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  Abstract 


Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive condition, often irreversible. The chances of peripheral nervous system getting affected by the antineoplastic drugs are very high as compared to that of the central nervous system. Hence, this study is planned to assess the occurrence among cancer patients.
Purpose: The objective of the present study was to screen patients undergoing cancer treatment for CIPN.
Design: This was an observational study.
Setting: The study was conducted at a tertiary care cancer hospital.
Patients: Twenty-six individuals with CIPN, 30 years and above, were assessed using the modified total neuropathy score (mTNS) of >5.
Measurements: Patients were assessed using mTNS.
Results: Statistical analysis was done and it was found that 20% who received the drug cisplatin and 32% who received paclitaxel had CIPN. Forty-eight percent (48%) of the participants with CIPN received a combination of drugs.
Conclusion: The drug paclitaxel was a major source for causing neuropathy. Neuropathy was seen when paclitaxel was given as the soul drug and also when given in combination with carboplatin.

Keywords: Neoplastic, neuropathy, oxidative stress, paclitaxel


How to cite this article:
Fernandes J, Kumar S. Occurrence of chemotherapy-induced peripheral neuropathy in cancer patients at Belagavi city: An observational study. Physiother - J Indian Assoc Physiother 2017;11:17-20

How to cite this URL:
Fernandes J, Kumar S. Occurrence of chemotherapy-induced peripheral neuropathy in cancer patients at Belagavi city: An observational study. Physiother - J Indian Assoc Physiother [serial online] 2017 [cited 2017 Sep 24];11:17-20. Available from: http://www.pjiap.org/text.asp?2017/11/1/17/213273




  Introduction Top


Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling condition occurring as a side effect of cancer treatment. Once CIPN develops, cancer treatment has to be controlled or stopped, leading to cancer-related morbidity and mortality.[1] It is a progressive condition, often irreversible.[2] The neoplastic drugs which are responsible for causing CIPN include platinum drugs such as cisplatin, carboplatin, and oxaliplatin; taxanes including paclitaxel, docetaxel, and cabazitaxel; epothilones, such as ixabepilone; plant alkaloids, such as vinblastine, vincristine, vinorelbine, and etoposide; thalidomide, lenalidomide, and pomalidomide; bortezomib and carfilzomib; and eribulin.[3]

The incidence of peripheral neuropathy in the western countries with taxane class of drugs that is paclitaxel is 60%, docetaxel is 50%, and abraxane is 71%. The incidence of peripheral neuropathy with vinca alkaloids such as vinorelbine is 25% and vincristine is not listed. The incidence with platinum compounds such as cisplatin is not listed but with carboplatin is 4% and oxaliplatin is 74%.[4]

The chances of peripheral nervous system (PNS) getting affected by the antineoplastic drugs are very high as compared to that of the central nervous system (CNS). This is because the PNS is not effectively protected as that of CNS. Common site of affection is the dorsal root ganglia of the primary sensory neuron.[5] CIPN-induced nerve injury is due to axonopathy.[6]

Due to the higher metabolic requirement,[7] the longest nerves are highly susceptible to neurotoxic effects of cancer treatment.[8] Clinically, “stocking and glove” distribution of sensory-motor symptoms is seen. Symptoms develop initially in the feet and hands, followed by proximal progression to the ankles and wrists.[9] Other signs and symptoms include numbness, tingling, pins and needles, burning, decreased or altered sensation, or increased sensitivity that may be painful in the feet and hands.[10],[11],[12],[13],[14] Pain is often described as burning, electric shock-like, freezing type of pain. Allodynia, where normal touch is painful or hyperpathia where painful sensations are perceived as excruciating, can also be seen in patients with CIPN.[15]

A growing amount of medical evidence strongly suggests that the incidence of CIPN is significantly underreported in clinical trials.[16] More stress is on the malignancy and less on the associated physical symptoms often hampering the quality of life of the cancer patient. Hence, the objective of the present study was to screen patients undergoing cancer treatment for CIPN.


  Methods Top


The study was conducted over a period of 6 months at a tertiary care hospital after taking required ethical clearance from the Research Ethics Committee of the University. Written informed consent was taken from each participant. A total of 122 participants were screened, out of which 26 were diagnosed as having CIPN. One participant refused to give details. The inclusion criteria were as follows: (1) 30 years and above, (2) both males and females, and (3) undergoing chemotherapy and radiation therapy. The exclusion criteria were as follows: (1) CNS dysfunction (hemiparesis, myelopathy, and cerebellar ataxia), (2) previous history of PNS pathology, and (3) not willing to participate in the study.

Procedure

Participants were assessed for neuropathy due to CIPN using modified total neuropathy score (mTNS). Participants were asked to lie down in supine lying position and asked whether he/she felt any tingling, numbness, or neuropathic pain in the lower limbs. The worst of the above three symptoms mentioned was taken as the extension score which was the first subcomponent of the scale. The second and third subcomponent was pin sensibility, and vibration testing was checked using a cotton swab and 128 Hz tuning fork in the lower extremity from distal to proximal. Muscle strength was checked which is the fourth subcomponent. In this, the strength of the muscle with the worst score was taken. It included muscles of the toe, ankle, quadriceps, and hamstrings. The last component was tendon reflexes. Ankle jerk and knee jerk were checked bilaterally using a reflex hammer. Minimum score of 5 was required to be diagnosed as having neuropathy. Maximum score could go up to 20.

Data analysis

The demographic data were analyzed using mean and standard deviation [Table 1]. t-test was used to check for level of significance of the demographic data. Level of significance was set at P < 0.05. Distribution of participants having CIPN based on the drug was calculated in terms of percentage. Difference between males and females was also calculated.
Table 1: Demographic data

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  Results Top


Totally 122 participants were screened, out of which 26 participants were found to have CIPN. One refused to give details. Hence, analysis of 25 participants was done. On assessing the age, the mean age was 47.6 ± 12. When compared between gender, P value was 0.17, suggesting that the sample was homogeneous. Similarly, weight, body mass index (BMI), and mTNS had no difference. Whereas some difference in height was found and P value was significant, which maybe a contributing factor for more occurrence of CIPN in male participants [Table 1].

In our study, we found that 20% who received the drug cisplatin and 32% who received paclitaxel had CIPN. About 48% of participants with CIPN received a combination of drugs which includes carboplatin and paclitaxel and also etoposide, ifosfamide, flora, leucovorin and Arsenic Trioxide [Table 2].
Table 2: Distribution of male and female with drug received

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We also screened the patients receiving chemotherapy and radiation therapy. About 20% (n = 5) of participants received radiation along with cancer therapy, out of which 2 were male and 3 were female [Table 3].
Table 3: Distribution of male and female with status of radiation

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  Discussion Top


In the present study, CIPN was seen higher in participants who received combination of cancer drugs. The number of females with CIPN who received cisplatin or paclitaxel was more as compared to that of the males. This may be attributed to radiation therapy as more number of females received radiation as compared to that of males. However, high number of males had CIPN after receiving combination of drugs.

The participants included in the present study were 30 years and above. However, 18 out of 25 participants were above 40 years of age. A study on peripheral neuropathies with chemotherapeutics found that the incidence of CIPN was seen more with advancing age due to axonal loss which led to sensory and balance problems.[17] As a result of which, with the fear of fall, the patient prefers to stay on bed and not get involved in any kind of physical activity. This reduces endurance, contributing to fatigue. They may have less social interaction as they prefer to stay indoors.

In the present study, the BMI was within 18.5–24.9. In patients with non metastatic cancer having CIPN, BMI and body surface area (BSA) were not independently associated with the risk of treatment modification that includes chemotherapy dosing and distribution.[18]

A study to check whether CIPN could be used as a predictor of neuropathic pain in breast cancer patients found that out of 240 patients, 64% experienced CIPN during paclitaxel treatment. In this study, majority of the patients who were found to have CIPN were on paclitaxel treatment or combination of paclitaxel and carboplatin. And moreover, 7 patients were having breast cancer. The reason could be because of paclitaxel-related microtubule disruption which is present in the cytoplasm. Paclitaxel causes proliferation and disruption of normal functions of cell because of the formation of abnormal bundles of microtubules which bring about a desired effect on the tumor, but it can be harmful to normal tissues. Microtubules are necessary for maintaining structural functions of the nerves.[19]

The reason for CIPN could be oxidative stress in patients receiving chemotherapy, the antioxidant machinery (e.g., plasma glutathione [GSH] and α- and γ-tocopherol concentrations) decreased, and the GSH redox state became more oxidized. This imbalance manifests itself as a mediator of inflammatory pain. There is severe cell death of sensory neurons derived from dorsal root ganglion following increase in oxidative stress with the use of the anticancer drug cisplatin. Oxidative stress is also found to harm the autonomic nervous system and manifests itself in symptoms such as hearing loss.[20]

It is said that chemotherapy along with radiation therapy can cause long-term side effects that do not go away. One of them is neuropathy. In the present study, only five participants received radiation with antineoplastic drugs. Hence, the neuropathy seen in the other 20 participants is purely due to chemotherapy.[21] The first limitation of the study is the small sample size, one cannot generalize the result. The second limitation is that the study is done over a short period of time.


  Conclusion Top


The drug paclitaxel was associated with neuropathy. Neuropathy was seen when paclitaxel was given as the soul drug and also when given in combination with carboplatin. Since the physical symptoms are often ignored, all individuals undergoing chemotherapy especially using the drug paclitaxel should undergo a thorough sensory-motor assessment. In the future, multicenter study on occurrence on CIPN has to be undertaken.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Nat Rev Neurol 2010;6:657-66.  Back to cited text no. 1
    
2.
Grisold W, Oberndorfer S, Windebank AJ. Chemotherapy and Polyneuropathies. Vol. 12. European Association of Neurooncology Magazine; 2012.  Back to cited text no. 2
    
3.
American Cancer Society. Peripheral Neuropthy Caused by Chemotherapy. Available from: http://www.cancer.org/acs/groups/cid/documents/webcontent/002908-pdf.pdf. [Last updated on 2015 Mar 18; Last cited on 2015 Oct 20].  Back to cited text no. 3
    
4.
Meredith AW, Ernst HR. Chemotherapy-Induced Peripheral Neuropathy Fact Sheet. Available from: http://www.oncologypt.org/pdfs/fact-sheets/CIPN-Factsheet.pdf. [Last accessed on 2016 Oct].  Back to cited text no. 4
    
5.
Argyriou AA, Bruna J, Marmiroli P, Cavaletti G. Chemotherapy-induced peripheral neurotoxicity (CIPN): An update. Crit Rev Oncol Hematol 2012;82:51-77.  Back to cited text no. 5
    
6.
Gilardini A, Avila RL, Oggioni N, Rodriguez-Menendez V, Bossi M, Canta A, et al. Myelin structure is unaltered in chemotherapy-induced peripheral neuropathy. Neurotoxicology 2012;33:1-7.  Back to cited text no. 6
    
7.
Mironov SL. ADP regulates movements of mitochondria in neurons. Biophys J 2007;92:2944-52.  Back to cited text no. 7
    
8.
Gutiérrez-Gutiérrez G, Sereno M, Miralles A, Casado-Sáenz E, Gutiérrez-Rivas E. Chemotherapy-induced peripheral neuropathy: Clinical features, diagnosis, prevention and treatment strategies. Clin Transl Oncol 2010;12:81-91.  Back to cited text no. 8
    
9.
Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C. Chemotherapy-induced peripheral neuropathy: Prevention and treatment strategies. Eur J Cancer 2008;44:1507-15.  Back to cited text no. 9
    
10.
Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol 2002;249:9-17.  Back to cited text no. 10
    
11.
Hilkens PH, ven den Bent MJ. Chemotherapy-induced peripheral neuropathy. J Peripher Nerv Syst 1997;2:350-61.  Back to cited text no. 11
    
12.
Weiss RB. Miscellaneous toxicities. In: DeVita VT Jr., Hellman S, Rosemberg SA, editors. Cancer: Principles and Practice of Oncology. 7th ed., Vol. 2, Ch. 54. Philadelphia: Lippincott Williams and Wilkins; 2005. p. 8.  Back to cited text no. 12
    
13.
Peltier AC, Russell JW. Recent advances in drug-induced neuropathies. Curr Opin Neurol 2002;15:633-8.  Back to cited text no. 13
    
14.
Corbo M, Balmaceda C. Peripheral neuropathy in cancer patients. Cancer Invest 2001;19:369-82.  Back to cited text no. 14
    
15.
Fernandez C, Mehta Z, Espenlaub A, Ellison N. Chemotherapy-induced peripheral neuropathy. J Palliat Med 2014;17:965-6.  Back to cited text no. 15
    
16.
Perry MC, Doll DC, Peter C. Chemotherapy-induced peripheral neuropathy. Perry's the Chemotherapy Source Book. 5th ed., Ch. 22. Philadelphia: Lippincott Williams and Wilkins; 2010. p. 257-90.  Back to cited text no. 16
    
17.
Grisold W, Cavaletti G, Windebank AJ. Peripheral neuropathies from chemotherapeutics and targeted agents: Diagnosis, treatment, and prevention. Neuro Oncol 2012;14 Suppl 4:iv45-54.  Back to cited text no. 17
    
18.
Mols F, Beijers T, Lemmens V, van den Hurk CJ, Vreugdenhil G, van de Poll-Franse LV. Chemotherapy-induced neuropathy and its association with quality of life among 2- to 11-year colorectal cancer survivors: Results from the population-based PROFILES registry. J Clin Oncol 2013;31:2699-707.  Back to cited text no. 18
    
19.
Jain KK, editor. Drug-induced peripheral neuropathies. In: Drug-induced Neurological Disorders. 2nd ed. Seattle: Hogrefe and Huber; 2001. p. 263-94.  Back to cited text no. 19
    
20.
Han Y, Smith MT. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). Front Pharmacol 2013;4:156.  Back to cited text no. 20
    
21.
Photetica. Side Effects and Quality of Life with CIPN, Chemotherapy Induced Peripheral Neuropathy, Diabetic Peripheral Neuropahty, and Peripheral Neuropathy. Available from: http://www.photetica.com/Side-Effects-and-Quality-of-Life-With-CIPN-Chemoth.html. [Last accessed on 2016 Oct].  Back to cited text no. 21
    



 
 
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