Prevalence of Paclitaxel Induced CIPN-Related Pain and CIPN in Indian Patients With Breast Cancer

Study Overview
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Brief Summary
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Since its introduction in the 1970s, Paclitaxel has been used as an effective anticancer agent against lung, breast, ovarian, leukopenia and liver cancer. But, Paclitaxel-induced peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Paclitaxel induced peripheral neuropathy most commonly presents as Pain Burning, Tingling (pins and needles feeling) or electric/shock-like pain, Hyperalgesia, Allodynia, Increased sensitivity to cold or heat These symptoms are classically seen symmetrically in the distal extremities (glove and stocking distribution). Most adverse effects associated with chemotherapy are ameliorated after cessation of the therapy, but CIPN may persist in the longterm, with 30 % patients having CIPN related symptoms beyond 6 months after completion of chemotherapy7.Understanding the epidemiology of neuropathic pain in breast cancer patients has high clinical and public health significance.

Detailed Description
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PRIMARY AIM / OBJECTIVE: Our study aims to observe the prevalence of CIPN-related pain in cancer breast patients who have received Paclitaxel based adjuvant chemotherapy where we define CIPN-related pain as - possible neuropathic pain in patients scoring more than 12 on Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS). SECONDARY AIM / OBJECTIVE Since its introduction in the 1970s, Paclitaxel has been used as an effective anticancer agent against lung, breast, ovarian, leukopenia and liver cancer. But, Paclitaxel-induced peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Paclitaxel induced peripheral neuropathy most commonly presents as Pain Burning, Tingling (pins and needles feeling) or electric/shock-like pain, Hyperalgesia, Allodynia, Increased sensitivity to cold or heat These symptoms are classically seen symmetrically in the distal extremities (glove and stocking distribution). Most adverse effects associated with chemotherapy are ameliorated after cessation of the therapy, but CIPN may persist in the longterm, with 30 % patients having CIPN related symptoms beyond 6 months after completion of chemotherapy7.Understanding the epidemiology of neuropathic pain in breast cancer patients has high clinical and public health significance. MATERIALS & METHODS: The cohort will consist of women with early breast cancer (stages I through III) who had received Paclitaxel chemotherapy for breast cancer as per the Institutional guidelines within the preceding two years. History suggestive of pre-existing neuropathy will be noted. All patients (who fulfill the inclusion criteria) visiting Tata Memorial hospital during Feb2017 2016 to June 2017 will be examined in the Medical Oncology OPD by one of the investigators and the current CIPN and CIPN-related pain score will be documented by using the NCI-CTCAE and LANSS scale. Then, the patients will be questioned for thepresence of similar neuropathic symptoms before starting, after starting and during Paclitaxel the chemotherapy and their replies will be recorded in the. Patients who had received adjuvant chemotherapy with Paclitaxel but who could not complete their chemotherapy due to Paclitaxel induced adverse effects other than peripheral neuropathy for eg hypersensitivity to Paclitaxel will be screened but their data will be excluded from final data assessment. 2. Use of 1. Acetyl-L-carnitine (ALC) 2. Amifostine 3. Amitriptyline 4. CaMg 5. Diethyldithio-carbamate (DDTC) 6. Glutathione (GSH) 7. Nimodipine 8. All-trans-retinoic acid 9. rhuLIF 10. Vitamin E during Paclitaxel chemotherapy will be noted based on history and examination of charts. For CIPN-related pain: The Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS) is a simple and valid 7-item tool for identifying patients whose pain is dominated by neuropathic mechanisms. Each item is a binary response (yes or no) to the presence of symptoms (5 items) or clinical signs (2 items). If score > 12, neuropathic mechanisms are likely to be contributing to the patient's pain. NCI-CTCAE : The National Cancer Institute - Common Terminology Criteria for Adverse Events v4.0, NCI-CTCAE most recently updated in 2010, will be used for grading CIPN. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for CIPN. Paclitaxel induced CIPN is defined as NCI-CTCAE Grade 2 or above.

Official Title
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Prevalence of Paclitaxel Induced CIPN-Related Pain and CIPN in Indian Patients With Breast Cancer : A Prospective Observational Study

Conditions
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Breast Cancer Female, Neuropathic Pain

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically confirmed Primary breast cancer Patients who had received adjuvant chemotherapy with Paclitaxel and who have completed their Paclitaxel chemotherapy within the preceding 2 years i.e. between 1stAugust 2014 to 31st July 2016. Exclusion Criteria: Age below 18 years On current Paclitaxel chemotherapy Patients with radiological evidence of bone metastases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of Paclitaxel induced CIPN-related pain | CIPN-related pain is defined as - neuropathic pain as a result of chemotherapy induced nerve damage . All patients (who fulfill the inclusion criteria) visiting Tata Memorial Hospital during Feb2017 to Jun2017will be examined in the Medical Oncology OPD by one of the investigators and the current CIPN-related pain score will be documented by using the LANSS scale. LANSS score>12 will be considered as possible CIPN-related pain for statistical analysis | 2 years post Paclitaxel Chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of Paclitaxel induced CIPN | CIPN defined as - neuropathy symptoms (other than pain) as a result of chemotherapy induced nerve damage . All patients (who fulfill the inclusion criteria) visiting Tata Memorial Hospital during Feb2017 to Jun2017will be examined in the Medical Oncology OPD by one of the investigators and the current CIPN score will be documented by using the NCI-CTCAE v4.0 grading. Paclitaxel induced CIPN is defined as NCI-CTCAE Grade 2 or above for statistical analysis | 2 years post Paclitaxel Chemotherapy | 
| temporal characteristics and risk factors of CIPN-related pain | The distribution, appearance and disappearance of syptoms related to CIPN will be based on special questionnaire. | 2 years post Paclitaxel Chemotherapy | 
| Use of Agents offered with an intend to prevent CIPN | Use of 1. Acetyl-L-carnitine (ALC) 2. Amifostine 3. Amitriptyline 4. CaMg 5. Diethyldithio-carbamate (DDTC) 6. Glutathione (GSH) 7. Nimodipine 8. All-trans-retinoic acid 9. rhuLIF 10. Vitamin E during Paclitaxel chemotherapy will be noted based on history and examination of charts | 2 years post Paclitaxel Chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuropathic Pain, Paclitaxel, CIPN