Oxaliplatin induced peripheral neuropathy and associated factors among colorectal cancer patients in Tanzania

doi:10.21203/rs.3.rs-4960021/v1

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Oxaliplatin induced peripheral neuropathy and associated factors among colorectal cancer patients in Tanzania

https://doi.org/10.21203/rs.3.rs-4960021/v1

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Background

Colorectal cancer (CRC) is one of the leading malignancies globally and chemotherapy forms the bulk of its management. Oxaliplatin is one of the standard drugs used for management of colorectal cancer. Oxaliplatin induced peripheral neuropathy (OIPN) is one of the most debilitating toxicities encountered which lead to dose modification and premature treatment discontinuation with a great impact on quality of life. Therefore, we armed to determine the prevalence, severity and factors associated with OIPN among colorectal cancer patients treated in Tanzania.

Methods

This was a cross-sectional study conducted at Ocean Road Cancer Institute (ORCI) to all histologically confirmed CRC patients who were on oxaliplatin-based chemotherapy regimens. Data was collected using EORT-QLQ CIPN20 questionnaire and analysis was done using SPSS version 23 and p value < 0.05 was considered statistically significant.

Results

A total of 62 patients were recruited, the prevalence of OIPN was 71% and 59.7% for acute and chronic symptoms respectively. Obese patients were 21.66 times higher at risk of suffering from chronic OIPN compared to individuals who have normal body weight (p < 0.05). Cumulative Dose ≤ 780 showed a protective effect (p < 0.005) in development of OIPN. For the severity of acute OIPN, it was found that 4.8% had grade 4 symptoms, while 8.1% had grade 3 symptoms, and 69.4% had grade 2 symptoms, and 17.7% of the patients had grade 1. In patients with chronic OIPN, 13.5% had grade 3 neuropathies, 24.3% had grade 2 and 62.2% had grade 1 neuropathy.

Conclusion

The prevalence of acute and chronic OIPN among colorectal cancer patients managed at ORCI was 71.0% and 59.7% respectively, with most patients developing grade 1 and 2 neuropathy for both acute and chronic symptoms. Number of cycles, cumulative dose and BMI were the major factors associated with the neuropathy.

Colorectal cancer

Peripheral neuropathy

Oxaliplatin

Ocean Road Cancer Institute

Globally, Colorectal cancer is among the most frequently occurring malignancies after breast, lung and prostate cancer(1)⁠. The incident of colorectal cancer is highest in both developed and developing worlds but mortality is more pronounced in the developing world. In East Africa, the data from Globocan 2020 shows 18,306 new cases and 13,236 deaths, whereas in Tanzania, colorectal cancer was ranked fourth with approximately 2,354 new cases in 2020 and an estimated mortality of 1,555 cases in the same year(1).

The management of colorectal cancer ranges from surgery, chemotherapy and radiotherapy which could be applied singly or in combination. Although colorectal cancer has a long preclinical progression which gives room to early diagnosis and so less aggressive treatment, most of the patients present to the hospital at advanced stage due to the nature of the disease in that it has less early symptoms making most patient advance in stage and definitely be candidates for chemotherapy(2, 3).

Discovery and licensing of oxaliplatin as an essential drug used in management of patients with colorectal cancer is one of major advances that changed the management and eventual outcome of patients with colorectal cancer. It started off to being included in the treatment regimen for patients with metastatic disease after it showed promising results. It was later included as a pivotal mainstay drug used even in non-metastatic cancer patients. Due to the good treatment response and combination with other drugs, patients are now living longer than earlier anticipated even though there are toxicities associated with its use.

Peripheral neuropathy is one of the most debilitating and dose limiting toxicity of Oxaliplatin and this has been widely articulated in literature to occur in almost 85%-95% of the patients. These oxaliplatin induced peripheral neuropathy (OIPN) could be featured into two discrete forms, acute type which is short-lived and chiefly occurs in sensory form and might be triggered by cold exposure. The acute form has swift inception and persists briefly from hours to few days after treatment and is majorly reversible(4). The other is the chronic type, which is characterized by steady and progressive onset with the chance of occurrence increasing with the cumulative dose of oxaliplatin(5). Furthermore, the chronic type is also sensory in nature and is accompanied by sensory paresthesia’s and dysesthesias which could impair day-to-day activities and quality of life of patients(6–11).

No current management is available for OIPN and the only accessible medications are for symptoms mitigations to the elements of neuropathic pain(12, 13). Among multiple methods that have been investigated to manage OIPN, duloxetine was found useful in management of oxaliplatin-associated neuropathic pain. Other medicines that have demonstrated to be effective include gabapentin, lamotrigine, and baclofen(14). With OIPN reversibility in the majority of patients, several facilities have used a stop-and-go strategy to try and minimize the side effect. Two trials showed that the prevalence of neuropathy was less if the intermittent administration is given and hence minimize toxicity in patients who manifest with OIPN(15). At ORCI, for symptom management, gabapentin and vitamin B supplements are prescribed to curb the effect of neuropathy. Management of colorectal cancer is in two folds. For colon cancer the treatment consists of adjuvant chemotherapy which include FOLFOX regimen and for metastatic stage, FOLFOX or CAPOX regimen is used. For rectal cancer, neoadjuvant chemotheradiotherapy is used and consist of 5 fluorouracil plus leucovorin and radiotherapy followed by adjuvant chemotherapy. Modified FOLFOX 6 or 7 is used with or without bevacizumab in metastatic stage(16).

Despite the fact that oxaliplatin is widely used in our local setting to manage patients with colorectal cancer, there is scarcity of information about OIPN and its impact on patients at ORCI, Tanzania and sub-Saharan Africa at large. This study will shed light on OIPN as adverse effect of oxaliplatin in treatment of CRC at ORCI and the information will be used for additional guideline development and in identifying at risk patients for available prophylactic and supportive measures in the management of patients with CRC at ocean road and Tanzania at large.

Study design and subjects

This cross-sectional study enrolled 62 histologically confirmed patients with CRC who were on oxaliplatin-based regimen, given at least six cycles, aged 18 years or older and treated at ORCI from December 2021 to May 2022. Patients who have received other platinum/Taxane based chemotherapy previously and with pre-existing peripheral neuropathy prior to oxaliplatin therapy were excluded.

Social demographic and clinical information of the patients was extracted from the patients’ medical charts whereas other information regarding social demographic characteristics of the patients was supplemented by interviewing the patients. Questionnaires were used to interview and collect data. The questionnaire consisted of Social demographic, clinical profile of the patients and adapted questionnaires. In this study, two sets of questionnaires were adapted and used to screen for OIPN and quantify the severity. Prevalence of acute OIPN was assessed using descriptive questionnaire that was previously used in other studies, Nadeen T. Ali et al. (17).

The questionnaire consists of 11 questions that assess the temporary symptoms of peripheral neuropathy and the severity of OIPN was graded as the sum of number of symptoms. If the patients have 1–3 symptoms, the severity of acute OIPN was graded 1, if the sum of the symptoms is present between 4 and 6 then the severity was Grade 2 and if is 7–9 symptoms will be present then it was graded 3 and above 9 symptoms was graded as 4 (17).

EORT-CIPN20 questionnaire and Common terminology criteria for adverse events version 4.03. was used to screen and grade chronic OIPN respectively. This questionnaire has been used to assess chemotherapy induced peripheral neuropathy (CIPN) in many studies. It consists of sensory, motor and autonomic neurotoxicity subscale consisting of twenty questions items. Each item is measured on a Likert scale ranging from 1) Not at all to 4) Very much (17). The QLQ-CIPN20 was assessed using a simple additive checklist that yielded a single, mean total score. The raw mean of the 18 items (excluding the two conditional items; difficulty using the pedals and difficulty getting or maintaining an erection) was computed and linearly converted to a 0-100 scale, as per EORTC scoring methods for symptom scales. Patients with higher score indicated a higher level of symptom burden(18). Grading was done using Common terminology criteria for adverse events version 4.03 which has been broadly used to quantify the severity of chemotherapy induced neurotoxicity (15).

Muhimbili University of Health and Allied Sciences ethical review board (approval number: - MUHAS-REC-12-2021-913) provided ethical clearance and Permission to conduct the study at ORCI was sought from institutional ethical committee. Consent forms were given in written form to patient and for those who can’t write it was supplemented verbally.

Statistical analysis

Statistical Package for Social Science (SPSS v.23) was used in data analysis. Clinical and demographic data were analyzed using measures of descriptive statistics such frequency, percentage, mean and standard deviation. For Association between independent and dependent variable, univariate analysis (chi square) and multivariate analysis (logistic regression) was done.

Characteristics of study subject and severity of peripheral neuropathy

A total of 62 patients were recruited, the mean age of the patients was 52.47 with Standard deviation ± 14.05 years, and range between 19–77 years of age. More than half (59.7%) of patients were male and 28 (40.3%) were female with male to female ratio of 1.5:1. Based on the comorbidity status it was found that 22.6% of the patients were hypertensive, 6.5% diabetic and 6.5% seroconverted (HIV). In this study 58.1% of the patient were prescribed CAPEOX regimen while 41.9% used FOLFOX, of which 56.4% got more than seven cycles of chemotherapy. The prevalence of acute symptoms of OIPN was 71% and chronic OIPN symptoms were 59.7% of colorectal cancer patients who were treated at ORCI during the study period (Table 1).

The proportion of patients who had acute OIPN symptoms was also examined among CRC patient during chemotherapy treatment. Among the symptoms, throat discomfort (77.42%) and tingling in mouth (82.26%) and jaw pain (87.10%) had highest prevalence. However, there were 32, 45 patients who respectively experienced acute symptoms such as burning in eyes and feeling shock down the back. Minority of CRC patients had problem with breathing (9.68%) among others (Table 2). On grading of acute OIPN, majority of the patients had Grade 2 in 43 (69.4%), Grade 1 were 11 (17.7%) patients, Grade 3 were 5 (8.1%) patients with grade 4 in 3 patients (4. 8%) (Fig. 1). For the assessment of severity for Chronic OIPN among colorectal cancer patient n = 37 (59.7%); maximum grade was grade 3 in 5 (13.5%) patients, grade 2 in 9 (24.3%) and grade 1 in 23 (62.2%) patients. (Fig. 2)

Responses to the single items subscales of the QLQ-CIPN20 is shown in table. Among the symptoms assessed, the three most prevalent were, tingling sensation in fingers or hands (n = 5), tingling sensation of toes or feet (n = 2) and trouble opening jar (n = 2) which had high proportion of patients responding to very much on the Linkert scale. The study also revealed that 1.6% and below individuals could either experience one of the remaining symptoms or none at a relatively higher (very much) extent. Most other patient responded in great numbers to having less symptoms (a little) on the scale. 33.9% of the patient reported to have symptoms of feeling dizziness after standing up when compared to those who didn’t felt any symptoms of dizziness (Table 3).

Table 1

Baseline characteristics of patients with colorectal at ORCI (n = 62)
Baseline characteristics	Frequency	Percent
Gender
Male	37	59.7
Female	25	40.3
Age category (years)
< 40	13	21
40–59	27	43.5
≥ 60	22	35.5
Marital status
Single	15	24.2
Married	38	61.3
Divorced	1	1.6
Widowed	8	12.9
Education level
Primary	17	27.4
Secondary	25	40.3
College	20	32.3
BMI
under weight	6	9.7
normal weight	31	50
over weight	11	17.7
Obese	14	22.6
Cancer type
Colon	38	61.3
Colorectal	24	38.7
Histological type
Adenocarcinoma	61	98.4
Carcinoid	1	1.6
Cancer stage
Stage 2	7	11.3
Stage 3	34	54.8
Stage 4	21	33.9
Comorbidities
Hypertension
Yes	14	22.6
No	48	77.4
HIV/AIDS
Yes	4	6.5
No	58	93.5
Alcohol
Yes	34	54.8
No	28	45.2
Diabetes
Yes	4	6.5
No	58	93.5
Treatment factors
cumulative dose
≤ 780 mg/m2	38	61.3
> 780 mg/m2	24	38.7
Drug regime
FOLFOX	26	41.9
CAPEOX/XELOX	36	58.1
number of cycles
≤ 7	31	50
> 7	31	50

Table 2

Prevalence of acute neuropathic symptoms in patients using oxaliplatin
Symptoms	n	%
Tingling in mouth	51	82.26
Eyelid dropping	8	12.90
Throat discomfort	48	77.42
Difficulty with speech	23	37.10
Jaw pain	54	87.10
Muscle cramp	18	29.0
Problem with breathing	6	9.68
Burning in the eyes	32	51.61
Loss of vision	7	11.29
Shock down the back	45	72.58
Ear pain	13	20.97

Table 3

Responses to EORTC QLQ-CIPN20 items
EORTC QLQ-CIPN20	N(%)
Sensory symptoms and problems	Missing/NA	Not at all	A little	Quite a bit	Very much
Sensory scale
Tingling fingers or hands?	0	4 (6.5)	26(41.9)	27(43.5)	5(8.1)
Tingling toes or feet?	0	4(6.5)	26(41.9)	30(48.4)	2(3.2)
Numbness in fingers or hands?	0	5(8.1)	27(43.5)	29(46.8)	1(1.6)
Numbness in toes or feet?	0	4(6.5)	29(46.8)	28(45.2)	1(1.6)
Aching or burning pain in fingers or hands?	0	9(14.5)	35(56.5)	18(29.0)	0(0.0)
Aching or burning pain in toes or feet?	0	12(19.4)	28(45.2)	22(35.5)	0(0.0)
Trouble standing or walking?	0	22(35.5)	36(58.1)	4(6.5)	0(0.0)
Trouble distinguishing hot and cold water?	0	17(27.4)	34(54.8)	11(17.7)	0(0.0)
Trouble hearing?	0	48(77.4)	13(21.0)	1(1.6)	0(0.0)
Motor scale
Cramps in hands?	0	9(14.5)	26(41.9)	26(41.9)	1(1.6)
Cramps in feet?	0	8(12.9)	24(38.7)	29(46.8)	1(1.6)
Trouble holding a pen making writing difficult?	0	14(22.6)	30(48.4)	17(27.4)	1(1.6)
Trouble handling small objects (e.g. buttoning a blouse)?	0	9(14.5)	25(40.3)	28(45.2)	0(0.0)
Trouble opening jar/bottle due to loss of strength in hands?	0	9(14.5)	31(50.0)	20(32.3)	2(3.2)
Trouble walking because your feet come down to hard?	0	28(45.2)	33(53.2)	1(1.6)	0(0.0)
Trouble walking stairs or standing up from a chair due to weakness in legs?	0	19(30.6)	39(62.9)	4(6.5)	0(0.0)
Trouble driving due to use of pedals?	19(30.6)	19(30.6)	18(29.0)	6(9.7)	0(0.0)
Autonomic scale
Dizziness after standing up?	0	14(22.6)	27(43.5)	21(33.9)	0(0.0)
Blurry vision?	0	53(85.5)	7(11.3)	2(3.2)	0(0.0)
Only for males; Trouble getting or maintaining an erection?	25(40.3)	11(17.7)	19(30.6)	6(9.7)	1(1.6)

Association of chronic OIPN and baseline variables

chi-square test of independence was performed. Cumulative dose, BMI and number of cycles were the variables that were significantly associated with OIPN toxic effect in patients with colorectal cancer (p < .05). Patients who receive relative high cumulative dose (> 780mg/m²) seem to be more likely to develop OIPN toxic symptoms (83.33%) compared to individuals who receive doses ≤ 780mg/m² (44.74%) with p < .05. The analysis further showed that the number of cycles the patients received attributes to OIPN chronic toxicity. Similar pattern was observed for the case of BMI categories, there were more obese patients who developed OIPN toxicity (85.71%), followed by over weight (72.73%) compared to their respective categories (14.29% and 27.27%) who did not experience OIPN toxicity (Table 4).

Multivariate analysis was conducted using a binary logistic regression to determine factors independently contributing to OIPN toxic symptom. The logistic regression was performed to test effects of cumulative dose, number of cycles, hypertension and BMI variables on Oxaliplatin induced peripheral neuropathy symptomatic toxicity. Results indicated that the model was statistically significant finding, χ2(6, N = 62) = 26.53, p = .001. The correct prediction rate was about 82.3%. The Wald tests showed that all the variables significantly predicted the dependent variable (OIPN toxicity). This inferred that number of cycles, cumulative dose and BMI were risk factors of OIPN chronic toxicity. However, hypertension was not associated to OIPN chronic toxicity among patients with colorectal malignancies.

The adjusted odds ratio of developing OIPN among patients who received ≤ 7 cycles was 0.227 less compared to those who received more than 7 cycles, meaning that patients who receive less cycles are at lower risk of developing OIPN than at those who receive 7 and more cycles (p < .05). In assessing relationship between BMI of the patients with colorectal cancer and OIPN toxicity after chemotherapy treatment, logistic regression test results revealed that BMI was a significant predictor of chronic OIPN toxicity (p < .05). Furthermore, the model also revealed that colorectal cancer patients who are obese were 21.66 times higher at risk of suffering from chronic OIPN compared to individuals who have normal body weight (OR = 21.66, 95% CI (2.574, 182.244), p < 0.05). On the other end from this study it was found that Cumulative Dose showed predictive effect on OIPN toxicity. For instance, during chemotherapy treatment patients who receive lower doses (≤ 780mg/m²), their odds of developing chronic OIPN toxicity were lower than patients who received higher dose (> 780mg/m²) (Table 5).

Table 4

The association of chronic OIPN and baseline variables
Variable	Chronic OIPN				Total	ꭓ²	P
	No		Yes
	N	%	N	%
Gender
Male	13	35.14	24	64.86	37	1.026	0.311
Female	12	48.00	13	52.00	25
Age category (years)
< 40	6	46.15	7	53.85	13	0.973	0.615
40–59	9	33.33	18	66.67	27
≥ 60	10	45.45	12	54.55	22
Cumulative dose (mg/m²)
≤ 780mg/m2	21	55.26	17	44.74	38	9.106	0.003**
> 780mg/m2	4	16.67	20	83.33	24
WHO BMI classification
under weight	4	66.67	2	33.33	6	7.996	0.039**
normal weight	16	51.61	15	48.39	31
over weight	3	27.27	8	72.73	11
Obesity	2	14.29	12	85.71	14
Number of cycles
≤ 7	17	54.84	14	45.16	31	5.429	0.020**
> 7	8	25.81	23	74.19	31
Alcohol
Yes	13	38.24	21	61.76	34	0.166	0.683
No	12	42.86	16	57.14	28
HTN
Yes	3	21.43	11	78.57	14	-	0.129*
No	22	45.83	26	54.17	48
DM
Yes	1	25.00	3	75.00	4	-	0.642*
No	24	41.38	34	58.62	58
HIV/AIDS
Yes	2	50.00	2	50.00	4	-	1.000*
No	23	39.66	35	60.34	58
Drug regime
FOLFOX	12	46.15	14	53.85	26	0.633	0.426
CAPEOX/XELOX	13	36.11	23	63.89	36
Cancer type
Colon	12	31.58	26	68.42	38
Colorectal	13	54.17	11	45.83	24
Cancer stage
Stage 2	1	14.29	6	85.71	7		0.398*
Stage 3	15	44.12	19	55.88	34
Stage 4	9	42.86	12	57.14	21

*P values were calculated using Fischer’s exact test** significant at p = .05

Table 5

Factors predicting OIPN toxicity among CRC patients
Predictor	Wald (x²) test	AOR	95% CI		P
Predictor	Wald (x²) test	AOR	Lower	Upper	P
HTN
No	Ref
HTN(yes)	0.213	1.467	0.288	7.457	0.644
Number of cycles
> 7	Ref
≤ 7	3.999	0.227	0.053	0.971	0.046*
Cumulative Dose
> 780mg/m²	Ref
≤ 780mg/m²	7.943	0.104	0.022	0.502	0.005*
BMI classification
normal weight	Ref
under weight	0.006	1.089	0.121	9.799	0.939
over weight	3.98	6.586	1.034	41.963	0.046*
Obesity	8.009	21.66	2.574	182.244	0.005*

*significant at p < 0.5 level, AOR-adjusted odds ratio, CI-confidence interval

Colorectal cancer cases have been on the rise in sub-Saharan Africa in the past few years (1), making the use of oxaliplatin-based chemotherapy regimen as the mainstay in management of these cancer to increase. Oxaliplatin induced acute and chronic neuropathy is one of the dose limiting toxicities in management of CRC patients and to our best knowledge this is the first study in sub Saharan Africa to assess associated factors and severity of this side effect.

The finding from our study demonstrated that the prevalence of acute and chronic OIPN was 71.0% and 59.7% respectively among our patients. The mean age of the patients was 52.47 with standard deviation ± 14.05 years and most of the patients had stage 3 and 4 diseases, which can be attributed to late presentation due to asymptomatic early stages of colorectal cancer. Majority of the patients developed grade 1 (17.7%) and 2 (69.4%) neuropathy in both acute and chronic cases. Most patients reported symptoms of tingling in mouth (82.26%), throat discomfort (77.42%) and jaw pain (87.10%) for acute symptoms. The most prevalent symptoms reported by the patients in chronic OIPN was tingling of fingers (8.1%) and toes (3.2%) in its most severe form. This finding demonstrate a favorable comparison with many other studies done internationally(19–21). However, various factors such as study design, difference in study populations, and assessment tools used restrict comparisons between OIPN studies.

We also assessed the association of OIPN with age, Gender, number of cycles that the patient received, co-morbidities, Drug regime, Cancer stage and cumulative dose among others. The multivariate analysis of the results generally inferred that number of cycles, cumulative dose and BMI were independent risk factors of OIPN. This is in comparison with a systematic review study done by Jeremy. N .pulvers et al. (19).The trend showed that CAPEOX was associated with increased neurotoxicity symptoms and severe form in our study compared to FOLFOX regimen. This is in contrast to a study done by Baek KK et al where 266 patients were treated with FOLFOX every two weeks, and 79 received CAPEOX every three weeks. Their study found out that the chance of developing severe OIPN was significantly higher in those receiving FOLFOX compared to CAPEOX (p<0.01).(22). This difference with our study can be explained in that 58.1% of our patients received CAPEOX at a dose of 130 mg/m2 and the cumulative dosages at 6 cycles and above were higher compared to 41.9% who received FOLFOX.

Body mass index was strongly associated with OIPN where patients who are obese had higher prevalence and severity in our study. They were 21.66 times higher at risk of getting chronic OIPN symptoms compared to individuals who have normal body weight, this was statistically significant and gives an inference that the higher the BMI the more the risk of an individual in developing chronic OIPN symptoms during chemotherapy treatment. This finding was in agreement with a systemic review study done by Marry Jesse et al where twelve articles describing relationships between overweight/obesity and presence of chemotherapy induced peripheral neuropathy were analyzed. Associations between body mass index (BMI), body surface area (BSA), sarcopenic obesity and chemotherapy induced peripheral neuropathy incidence and severity were described in patients who had received platinum and taxanes compounds. Eleven out of 12 studies indicated increased incidence of peripheral neuropathy with higher BMI or BSA or sarcopenic obesity, and the two studies that analyzed severity of symptoms found an increase in those who were overweight/obese(23). The mechanisms influencing this relationship is related to increased dosing of chemotherapy related to a higher body surface area as well as the link of obesity with metabolic syndrome. The systemic inflammation often present with metabolic syndrome can lead to peripheral and central sensitization in the pain transmission system as well as axonal damage and demyelination of the nerves occurring as a result of proinflammatory cytokines(23).

Our study also took into consideration the severity of OIPN and found out that in for acute symptoms, 17.7% of the patients had grade 1, 69.4% had grade 2, 8.1% grade 3 and 4.8% grade 4. In Chronic OIPN 62.2% of the patients had grade 1 neuropathy, 24.3% grade 2 and 13.5% with grade 3. There is significant difference when compared with a study done by Sreenivasulu Palugulla et al:(24). where 219 patients were studied and the severity of both acute and chronic OIPN were assessed. The grade of acute OIPN was Grade1 in 70 (64.8%) patients, Grade 2 in 33 (30.5%) patients, and Grade 3 in 5 (4.6%) patients. For chronic OIPN, most of the patients had Grade 1 in 71 (55.9%) patients, Grade 2 in 54 (42.5%) patients, Grade 3 in 2 patients (1.5%).(24). There is obvious difference in severity for both the acute and chronic OIPN with grade 2 and 3 in our present study. The reason behind this may be due to the number of patient studied and possibly different genetic composition of patients in this studies.

In conclusion, the prevalence of acute and chronic Oxaliplatin induced peripheral neuropathy among colorectal cancer patients managed at ORCI was 71.0% and 59.7% respectively, with most patients developing grade 1 and 2 neuropathy for both acute and chronic symptoms and 4.8% developing grade 4 and 13.5% developing grade 3 for acute and chronic symptoms respectively. Number of cycles, cumulative dose and BMI were the major factors associated with the neuropathy and our findings is similar to other studies done globally.

CAPOX CAP = Capecitabine OX = Oxaliplatin

CIPN Chemotherapy Induced Peripheral Neuropathy

CRC Colorectal Cancer

DM Diabetes mellitus

FOLFOX FOL", Fluorouracil (5-FU) Folinic acid (leucovorin) ""F", and Oxaliplatin (Eloxatin) "OX

HIV Human Immunodeficiency Virus

HTN Hypertension

MCRC Metastatic Colorectal Cancer

MUHAS Muhimbili University of Health and Allied Sciences

OIPN Oxaliplatin Induced Peripheral Neuropathy

ORCI Ocean Road Cancer Institute

PN Peripheral neuropathy

RT Radiotherapy

SPSS Statistical Package of Social Science

TNS Total Neuropathy Score

Acknowledgement

We would like to thank the administration and personnel in the department of Clinical Oncology at Muhimbili University of Health and Allied sciences and Ocean Road Cancer Institute fraternity at large for their immense support during the study.

Author’s contributions

Concept design: MSG, ND, KKM. Administration support: ND, KKM. Provisional of study material and patients: MSG, EM. Data collection and assembly: MSG, EM. Data analysis and interpretation: MSG, EM. Manuscript writing, Final approval of manuscript and accountable for all aspects of the work: All authors.

Funding

There was no external source of funding for the study.

Availability of data and materials

The data set used and analyzed during the current study is available from the corresponding author upon reasonable request.

Ethics approval and consent to participate

Consent for publication

Not applicable

Completing interests

The authors declare no completing of interests.

Author details

¹Department of Clinical Oncology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. ²Academic, research and consultancy unit, Ocean Road Cancer Institute, Dar es Salaam, Tanzania. ³Department of Clinical Oncology, Rabininsia Memorial Hospital, Dar es Salaam, Tanzania

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 2021;71(3):209–49.
Garborg K, Holme, Løberg M, Kalager M, Adami HO, Bretthauer M. Current status of screening for colorectal cancer. Ann Oncol. 2013;24(8):1963–72.
Salvatore L, Aprile G, Arnoldi E, Aschele C, Carnaghi C, Cosimelli M et al. Management of metastatic colorectal cancer patients: Guidelines of the Italian Medical Oncology Association (AIOM). ESMO Open. 2017;2(1).
Argyriou AA, Cavaletti G, Briani C, Velasco R, Bruna J, Campagnolo M, et al. Clinical pattern and associations of oxaliplatin acute neurotoxicity: A prospective study in 170 patients with colorectal cancer. Cancer. 2013;119(2):438–44.
Zribi A, Nasr S, Ben, Hamdi S, Ayari J, Fendri S, Balti M, et al. Case series Oxaliplatin-induced peripheral neuropathy risk factors and management. panAfrican Med J. 2020;8688(35):1–6.
Hausheer FH, Schilsky RL, Bain S, Berghorn EJ, Lieberman F. Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol. 2006;33(1):15–49.
Lehky TJ, Leonard GD, Wilson RH, Grem JL, Floeter MK. Oxaliplatin-induced neurotoxicity: Acute hyperexcitability and chronic neuropathy. Muscle Nerve. 2004;29(3):387–92.
McWhinney SR, Goldberg RM, McLeod HL. Platinum neurotoxicity pharmacogenetics. Mol Cancer Ther. 2009;8(1):10–6.
Park SB, Goldstein D, Krishnan AV, Lin CS-Y, Friedlander ML, Cassidy J, et al. Chemotherapy-induced peripheral neurotoxicity: A critical analysis. CA Cancer J Clin. 2013;63(6):419–37.
Beijers AJM, Mols F, Vreugdenhil G. A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration. Support Care Cancer. 2014;22(7):1999–2007.
Petrioli R, Pascucci A, Francini E, Marsili S, Sciandivasci A, Tassi R, et al. Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: A randomized study of two different schedules of oxaliplatin. Cancer Chemother Pharmacol. 2008;61(1):105–11.
Argyriou AA, Polychronopoulos P, Iconomou G, Koutras A, Makatsoris T, Gerolymos MK, et al. Incidence and characteristics of peripheral neuropathy during oxaliplatin-based chemotherapy for metastatic colon cancer. Acta Oncol (Madr). 2007;46(8):1131–7.
Argyriou AA. Updates on oxaliplatin-induced peripheral neurotoxicity (OXAIPN). Toxics. 2015;3(2):187–97.
Schneider BP, Hershman DL, Loprinzi C. Symptoms: Chemotherapy-induced peripheral neuropathy. Adv Exp Med Biol. 2015;862:77–87.
Weickhardt A, Wells K, Messersmith W. Oxaliplatin-induced neuropathy in colorectal cancer. ASIA-PACIFIC J Oncol Nurs. 2011;7(3):266–72.
United THE, Of R, Health MOF, Development C. National-Cancer-Treatment-Guidelines2.pdf. 2020;1:88–97. http://kehpca.org/wp-content/uploads/National-Cancer-Treatment-Guidelines2.pdf
Postma TJ, Aaronson NK, Heimans JJ, Muller MJ, Hildebrand JG, Delattre JY, et al. The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: The QLQ-CIPN20. Eur J Cancer. 2005;41(8):1135–9.
Mols F, van de Poll-Franse LV, Vreugdenhil G, Beijers AJ, Kieffer JM, Aaronson NK, et al. Reference data of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 Questionnaire in the general Dutch population. Eur J Cancer. 2016;69:28–38.
Pulvers JN, Marx G. Factors associated with the development and severity of oxaliplatin-induced peripheral neuropathy: a systematic review. Asia Pac J Clin Oncol. 2017;13(6):345–55.
Ali N, Mohamed A, Yousef B. The Incidence of Oxaliplatin-Induced Peripheral Neurotoxicity at Khartoum Oncology Hospital: A Cross-Sectional Survey. Asia-Pacific J Oncol Nurs. 2020;7(3):266–72.
Shahriari-Ahmadi A, Fahimi A, Payandeh M, Sadeghi M. Prevalence of oxaliplatin-induced chronic neuropathy and influencing factors in patients with colorectal cancer in Iran. Asian Pac J Cancer Prev. 2015;16(17):7603–6.
Baek KK, Lee J, Park SH, Park JO, Park YS, Lim HY et al. Oxaliplatin-Induced Chronic Peripheral Neurotoxicity: A Prospective Analysis in Patients with Colorectal Cancer. 2010;42(4):185–90.
Jesse M. The Relationship of Chemotherapy- Induced Peripheral Neuropathy and Obesity: A Systematic Review. Rehabil Oncol. 2019;37(4):167–75.
Palugulla S, Dkhar SA, Kayal S, Narayan SK. Oxaliplatin-induced peripheral neuropathy in south indian cancer patients: A prospective study in digestive tract cancer patients. Indian J Med Paediatr Oncol. 2017;38(4):502–7.

No competing interests reported.

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Oxaliplatin induced peripheral neuropathy and associated factors among colorectal cancer patients in Tanzania

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Abstract

Background

Methods

Results

Conclusion

Figures

INTRODUCTION

Methodology

Study design and subjects

Statistical analysis

Results

Characteristics of study subject and severity of peripheral neuropathy

Association of chronic OIPN and baseline variables

Discussion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1