Chemotherapy-associated peripheral neuropathy is a common and serious consequence of cancer treatment. Because it is often the main reason for treatment reduction or discontinuation, it may affect survival by limiting the effectiveness of treatment. It will facilitate the screening of chemotherapy-induced peripheral neuropathies and their intervention in patients' daily lives [25]. Brouwers et al. (2009) reported in a pilot study that examined persistent neuropathy for up to six years after treatment with cisplatin and oxaliplatin that in patients who completed a cisplatin and oxaliplatin treatment regimen, peripheral neuropathy symptoms continued as chronic peripheral neuropathy in the lower extremities, particularly in the feet, and their quality of life was impaired [26]. Eckhoff et al. (2015) reported that in 15% of breast cancer survivors treated with docetaxel, there was a significant relationship between peripheral neuropathy symptoms observed 1-3 years after treatment [27]. Because there are no study data in the literature covering all four follow-up processes similar to our study, the follow-ups were evaluated individually. In our study, the duration of the neuropathy-related symptoms was found that they lasted no more than 1-3 days in F2 and no more than 3-7 days in F3 and F4. These times are thought to be dependent on a 7-day (weekly paclitaxel) cycle of treatment.
Sensory, motor, and autonomic symptoms are observed in CIPN associated with paclitaxel. These symptoms include stabbing-burning pain, burning, weakness, difficulty walking, balance, constipation, sexual dysfunction, tingling, numbness, and increased sensitivity to heat/cold [8, 9]. Furthermore, sensory neuropathy causes complaints of sensory disturbances in the patient's extremities, defined as "as if wearing socks and gloves" [5, 10, 11]. Symptoms usually begin at the fingertips and progress from distal to proximal [12–15]. Because these symptoms cause functional disorders in daily activities, they have a negative impact on patients' physical, social, emotional, and functional health and their quality of life [28]. In the study by Seretny et al. (2014), more than 60% of patients reported experiencing more or less severe symptoms of chemotherapy-induced peripheral neuropathy after the first month following completion of chemotherapy, and these symptoms lasted for a long time [29]. In our study, when comparing the symptom subdimensions according to the general average, sensory symptoms, motor symptoms, and manual dexterity activities increasing mean values of the symptom subdimensions were found in the ratings from F2 compared to F1, F3 compared to F1 and F2, F4 compared to F1, F2, and F3, which were statistically significant. We believe that these progressive changes in neuropathy subdimensions in recent cycles are due to the increase in cumulative dose.
In the Arabic version of the assessment tool for chemotherapy-induced peripheral neuropathy by Obaid et al. (2020), patients most frequently reported numbness in the fingers/feet and numbness in the fingers/hands as severity, distress, and frequency of symptoms (54.1% and 51.1%, respectively), followed by muscle or joint pain and tingling in the feet/toes (43.7% and 42.2%, respectively) [30]. According to our study, in the sub-dimensions of general mean, sensory symptoms, motor symptoms, and manual dexterity activities in the evaluations of F2 compared to F1, F3 compared to F1 and F2, F4 compared to F1, F2, and F3, the increasing mean scores of symptom sub-dimensions were found to be statistically significant, which is consistent with the literature.
In the study by Obaid et al. (2020), patients' responses to the frequency of symptom interaction items indicate that neuropathic symptoms affected walking, sleep, and usual housework in more than 40% of participants treated with neurotoxic chemotherapy. Neuropathic symptoms impaired enjoyment of life, exercise, participation in hobbies or recreational activities, and writing in more than 30% of participants treated with neurotoxic chemotherapy, with the least discomfort occurring during driving (18.5%) [30]. In our study, the smallest effect was in part about driving. We attribute this to the educational level of breast cancer patients (75.9% in primary school) and, accordingly, the proportion of drivers.
Hershman et al. (2011) reported that, the relationship between patient-reported outcomes and quantitative sensory testing to measure long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy, it was found that 81% of 50 breast cancer patients reported numbness in the hands or feet in the last week and 27% of these symptoms occurred in the hands, while 25% of them reported severe symptoms in the feet [31]. Considering that the first six questions of the CIPNAT scale, included sensory symptoms in our patient group, their severity and frequency gradually increased throughout the treatment period in processes F2, F3, and F4. This situation is thought to improve progressively depending on the cumulative dose of the paclitaxel treatment regimen.
In a retrospective 7-year, follow-up study examining the impact of oxaliplatin-induced peripheral neuropathy on health-related quality of life in survivors of colorectal cancer, Tofthagen et al. (2013) found that at least one symptom persisted in the posttreatment period, and the symptom of insomnia was significantly associated with the symptom of neuropathy [15]. The patients followed up for 25 months after oxaliplatin treatment, peripheral neuropathy symptoms continued to occur in 79.2% of patients, particularly sensory symptoms after treatment, and there was a significant correlation between neuropathy symptom scores and the cumulative dose of oxaliplatin administered [32]. In our study, although insomnia was most frequently observed at the first follow-up (without treatment), it also increased in F2 and F4. Insomnia that occurs without taking the first treatment cycle is thought to be due to the uncertainty and anxiety associated with chemotherapy. Insomnia that occurs with subsequent cycles is thought to be more related to the symptoms of neuropathy.
The association between age and taxane-based chemotherapy, treatment-related neurotoxic effects were reported to increase with age in elderly female patients with a mean follow-up of 8.5 years [33]. In our study it was found that the mean values during the four follow-ups (F1, F2, F3, F4) were not statistically significant. The inconsistency of age and neuropathy symptoms with the literature is because the mean age of patients in our treatment group was 46.10 years, and the percentages under 45 years and over 46 years were 43.0% and 57.0%, respectively.
Considering the cumulative doses of taxane-based drugs that cause peripheral neuropathy grade 2-4 peripheral neuropathy has been reported to occur due to paclitaxel treatment at an average dose of 715-1500 mg/m2 [24, 34]. The study that potential risk factors for falls in people with CIPN, including cumulative dose and number of cycles, severity of loss of balance, severity of muscle weakness, self-reported impairment in walking or driving, number of neuropathic symptoms, severity of CIPN, and performance [35]. Also, patients who had fallen scored significantly higher on the CIPNAT, including the number of symptoms, symptom life items, and intervention items, than patients who had not fallen [35]. In our study, the mean BSA was 1.70±0.01 and according to the neuropathy-related changes in the CIPNAT scale during the patients' paclitaxel regimen, the frequency of the motor symptoms subdimension and the mean of the F2, F3, F4 follow-ups are significantly higher than the F1 (p<0.05). This is hypothesized to increase with cumulative dose.
Although literature reviews have reported that some pharmacologic uses such as calcium and magnesium, as well as nonpharmacologic approaches such as acupuncture, massage, exercise, etc., may be beneficial, there are no uses with proven efficacy in the prevention or management [36]. According to our study, management of symptoms related to neuropathy it was found that our patients used religious practices, movement exercises, and rubbing methods (massage) from the nonpharmacological practices in F2, F3, and F4, and pharmacological procedures F2, F3, and F4 were determined to take paracetamol to manage neuropathy. In this context, it is thought that although data compatible with the literature are obtained, complete success in management has not been achieved.
Examining the studies in the literature to manage peripheral neuropathy and improvement of patients' quality of life, exercise is reported to reduce motor deficits in peripheral neuropathy, (tingling, numbness, and sensitivity to cold/heat) and neuropathic pain scores [37–40]. In a pilot study examining the effect of a somatic yoga and meditation intervention (SYM) on functional outcomes and quality of life, SYM was performed twice weekly for a period of 8 weeks; the intervention was found to contribute positively to functional measures of quality of life in patients with CIPN [41]. A randomized controlled study that included an individualized six-week moderate-intensity progressive home walking and resistance exercise program reported that patients receiving taxane, platinum, or vinca-alkaloid-based chemotherapy had decreased symptoms of CIPN, and an exercise program was recommended for these patient groups [42]. In the study which examined the association between chemotherapy-induced neuropathy and quality of life in colorectal cancer survivors 2 to 11 years later, it was reported that patients had neuropathy-related symptoms, particularly sensory symptoms in the lower extremities. Because neuropathy symptoms negatively affect the quality of life, the importance of screening for these symptoms is particularly emphasized [43]. In our study the symptoms that occurred during the cycle of paclitaxel and the data on the management of symptoms associated with neuropathy were examined, it was found that they used religious practices, movement exercises, and rubs (massages) in the nonpharmacological applications in F2, F3, and F4 and took paracetamol to manage neuropathy in the pharmacological methods in F2, F3, and F4. Although the data are consistent with the literature, the CIPNAT scale and quality of life scale indicate no complete success in management. Also, the relationship between peripheral neuropathy and quality of life in our study, also show the results of the symptom subdimension according to neuropathy-related changes in the CIPNAT scale and the symptom subdimension according to changes in the EORTC C30 QLQ during patients' paclitaxel regimen. According to the results of correlation analysis in both scales, the CIPNAT scale increased in evaluations F2 compared to F1, F3 compared to F1 and F2, F4 compared to F1, F2, and F3, while the dimensions of EORTC C30 QLQ statistically decreased. In addition, when the relationship between the neuropathy subdimension of manual dexterity in the CIPNAT scale and the functional subdimension of the EORTC C30 QLQ was examined, it was found that the mean scores during F2 and F4 were statistically significant. Thus, it was found that the increase in neuropathy symptoms negatively affects the quality of life. It was found that there was a negative relationship between sensory, motor, and hand skills and quality of life. This result of our study is consistent with the literature.