Online ISSN : 1687-8329

    




Quick Search 
 
Author  
Year    
Title  
Vol:  

 
 
July2010 Vol.47 Issue:      3 (Supp.) Table of Contents
Full Text
PDF


Clinical and Electrophysiological Assessment of Peripheral Neurotoxicity in Cancer Patients Treated with Paclitaxel Chemotherapy

El-Sayed A. Tag El-Deen1, Azza A. Ghali1, Samar G. Younis2

 

Departments of Neuropsychiatry1, Radiation Oncology2, Tanta University; Egypt

 



ABSTRACT

Background: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting side effect and can lead to severe disability. Objective: To study the clinical and electrophysiological findings of paclitaxel (taxane) induced peripheral neurotoxicity in cancer patients. Methods: The study included 34 patients scheduled to be treated with paclitaxel and paclitaxel-cisplatin based regimens according to cancer type. Patients were divided into 2 groups: The first included patients treated by paclitaxel as single agent and the second included patients treated with paclitaxel and cisplatin. Patients were clinically and electrophysiologically monitored during and 3 months after discontinuing the chemotherapy; via the Modified Peripheral Neuropathy (PNP) score. Results: Evidence of Polyneuropathy (PN) was disclosed in 25 patients of the 34 patients (73.5%) treated with paclitaxel –based chemotherapy. The mean score of PNP was significantly higher in patients of group II than in patients of group I. Moreover, it was significantly increased from the 3rd to 6th cycles of chemotherapy. Significant deterioration in the amplitude of sensory action potentials (a-SAPs) of both ulnar and sural nerves was seen from the 3rd to 6th cycles of treatment. Further progression of neuropathy after discontinuation of chemotherapy, as particularly demonstrated by the sensory conduction abnormalities, was evident in group II. Conclusion: Our results indicated that patients treated with either paclitaxel alone or in combination with cisplatin based regimens would manifest an axonal predominately sensory PN. Combination of taxane and cisplatin increase the severity of PN than taxane alone. Persistence of PN for at least 3 months after the discontinuation of paclitaxel-cisplatin based chemotherapy also should be expected. [Egypt J Neurol Psychiat Neurosurg. 2010; 47(3): 433-440]

 

Key Words: Neuropathy, electrophysiology, PNP score, paclitaxel, cisplatin.

 





INTRODUCTION

 

Taxanes are a class of chemotherapy agents that promote the polymerization of tubulin into highly stable and dysfunctional intracellular microtubules. These microtubules block mitosis in the late G2 mitotic phase of cell cycle and induce cell death1,2. The first taxane developed and tested in the field of oncology was paclitaxel3. The introduction of paclitaxel to the armamentarium of oncologic therapy in the early 1990s had a great impact on the standard of care in lung, breast, ovarian carcinoma and other solid tumors. Subsequent to this development, another taxane, docetaxel was introduced4. These agents have become a significant component of cancer care in the treatment of both early-stage disease and advanced disease. Unfortunately, taxane therapy is associated with side effects such as peripheral neuropathy, myelosuppression, arthralgias, myalgias, and skin reactions that may affect patient-

 

reported quality of life (QOL)5,6. As taxanes do not cross the blood brain barrier to any significant degree, central neurotoxicity is rare.7

Taxane-induced peripheral neuropathy (TIPN) is the main non-hematological dose-limiting side effect and can lead to severe disability obviously deteriorating the quality of life of cancer patients.  Symptoms of peripheral neuropathy usually begin during chemotherapy and may worsen after cessation of treatment8-10. Accordingly, TIPN may pose a challenge for the clinician to diagnose and manage11.

 

Aim of the work:

The aim of this work is to study the clinical and electrophysiological findings of paclitaxel induced peripheral neuropathy in cancer patients.

 

PATIENTS AND METHODS

 

This study was conducted in the Radiation-Oncology Department in co-operation with the Neurology Department in Tanta University Hospital during the period from October 2007 to April 2009. We studied 34 eligible patients, with confirmed non small cell lung cancer and metastatic breast cancer who were treated at the Clinical Oncology Department. Patients were divided into 2 groups. The 1st group included patients with metastatic breast cancer treated with single agent paclitaxel. The 2nd group included patients with non small cell lung cancer treated with paclitaxel and cisplatin. Both groups are age matched to exclude effect of age on our results.

Their age ranged from 32 to 61 years (mean was 44.8±7.4 years). Eligible patients had to meet the following criteria: (a) at least 18 years of age (b) satisfactory liver and renal function, (c) life expectancy 9 months, (d) Karnofsky performance status scale >70 and ability to understand medical advice, and (e) full clinical-pathological examination and good staging for the patients. All patients gave informed written consent prior to study entry.

Exclusion criteria included: ages greater than 75 years or less than 18 years,  complete bowel obstruction or the presence of symptomatic brain metastases, ventricular arrhythmia, congestive heart failure, or documented myocardial infarction, inadequate bone marrow function (WBC count < 3.0 x 109/L or platelet count < 100 x 109/L), inadequate renal function (serum creatinine  of no more than 1.25 x upper normal limit or creatinine clearance < 60 mL/min/1.73 m2), and inadequate liver function (serum bilirubin of no more than 1.25 x upper normal limit). Patients were excluded if they had history of PN (e.g. hereditary, nutritional, paraneoplastic, etc.), history of systemic diseases (e.g. diabetes mellitus, Systemic lupus erythematosis, etc.) that may induce PN, or if had evidence of PN disclosed at baseline screening. Patients with a second malignant disease, inadequacy of follow-up, or other serious medical conditions that would impair the ability of the patient to receive treatment protocol were also excluded.

 

Treatment

Patients with metastatic breast cancer were treated with single agent paclitaxel 175 mg/m2 administered as a 3-hour infusion; the schedule was repeated every 3 weeks. Patients with non small cell lung cancer were allocated to receive paclitaxel 175 mg/m2 administered as a 3-hour infusion followed by cisplatin at a dose of 75 mg/m2 administered by intravenous infusion over 6 hours. The schedule was repeated every 3 weeks. Patients who received the cisplatin-based regimen were admitted to the hospital, while the single agent paclitaxel regimen was administered to outpatients. Standard premedication was administered with dexamethasone 20 mg orally 12 hours before the chemotherapy and again 6 hours before chemotherapy. Diphenhydramine 50 mg intravenously (IV) and cimetidine 300 mg IV (or ranitidine 50 mg IV) were administered 30 minutes before the chemotherapy. Antiemetics were administered at the oncologist’s discretion. In addition, patients in the paclitaxel- cisplatin arm received pre- and post-chemotherapy hydration to avoid cisplatin-induced nephrotoxicity. Dose reduction was performed according to nadir and nadir duration. Most of the patients received six cycles of protocol treatment unless they developed progressive disease or unacceptable toxicity.

 

Investigations:
               In addition to neurological examination, the following parameters were assessed at baseline: Karnofsky performance status, weight, abdominal computed tomography (CT) and/or ultrasound scan, chest x-ray and/or CT, ECG, blood counts (hemoglobin, granulocytes, and platelets), creatinine or EDTA clearance, and chemistry (renal and liver function tests). All baseline parameters, except the clearance, chest x-ray, scans and ECG were performed before each cycle together with an assessment of neurological toxicity. Scans were performed when progressive disease was suspected on clinical examination. Blood counts were performed weekly. Scans were repeated every 3 months together with assessments of blood counts, chemistry, weight, performance status, toxicity and neurological examination. Follow-up visits were scheduled 3 months after the end of the treatment.

 

Neurological Examination:

A detailed medical history was taken. It included age, sex, previous or recent sensory-motor symptoms, history of diabetes mellitus, vasculitis, and family history of peripheral neuropathy. Neurological examination was performed. The clinical evaluation of neuropathy was based on a Modified Neurological Symptom Score (NSS) and Neurological Disability Score (NDS) proposed by Dyck and Thomas12. NSS selected symptoms such as weakness, numbness or pain, scoring them as present (1) or absent (0). Clinical signs (i.e.: cranial nerve function, joint position, pinprick and vibration sensation, muscle strength and deep tendon reflexes) were assessed using a modified version of the NDS ranging from 0 (no deficit) to 4 (absence of function/ severest deficit). Disturbances indicating autonomic dysfunction (i.e.: bladder or bowel disturbances, postural hypotension, altered perspiration, impotence and nighttime diarrhea) were also recorded.

 

Electro Physiological Studies:

Standard neuro-physiological examination was performed unilaterally and the widely accepted criteria of identification of abnormalities were employed. The following parameters were estimated: (i) “peak to- baseline” amplitude of compound muscle action potential (a-CMAP), distal motor latency (DML), motor conduction velocity (MCV) and F-wave minimum latency of ulnar and peroneal nerves; and (ii) “peak-to-peak” amplitude of sensory action potentials (a-SAP) and sensory conduction velocities (SCV) of ulnar (orthodromic technique) and sural nerves (antidromic technique and proximal segment). For longitudinal comparison of neuro-physiological variables, we adopted the widely accepted criteria of identification of abnormalities based on serial measurements on healthy human subjects13 that included: (1) slowing of MCV and SCV by more than 10 m/s (2) reduction of potential amplitude by at least 50% and (3) prolongation of F-wave minimum latency by at least 5 ms in the ulnar and by 7 ms in the peroneal nerves.

 

Peripheral Neuropathy Score:

Clinical and electrophysiological findings were summarized by means of a peripheral neuropathy score (PNP score), described by Chaudhry and associates 11. Mild, moderate and severe neuropathy was defined by PNP scores l-6, 7-12 and >12 respectively. A battery of the clinical and electrophysiological tests was repeated after the third and sixth course of chemotherapy. To determine the evolution of neuropathy in paclitaxel-based chemotherapy, all patients were followed up for 3 months after the suspension of chemotherapy.

 

Statistical Analysis

Descriptive statistics were generated for all variables. The changes in mean clinical and electrophysiological scores both during chemotherapy and between the last course of chemotherapy and 3 months after its cessation were examined using paired-samples t -tests. Also, unpaired t-test was used to compare the mean clinical and electrophysiology scores between two groups. All tests were two sided, and significance was set at the P < 0.05 level. The SPSS for Windows was used to perform the statistics.

 

RESULTS

 

During the course of treatment, Clinical and/or electrophysiological evidence of PN was disclosed in 25 of the 34 patients (73.5%). There were 14 patients with metastatic breast cancer in group I treated with paclitaxel as a single agent and 11 patients with lung [non-small cell] cancer in group II treated with combined paclitaxel and cisplatin. In the first group; patients were treated per each one of the six chemotherapy courses with paclitaxel 175 mg/m2 based regimens every 3 weeks. In the second group, in addition to paclitaxel, patients were treated per each one of the six chemotherapy courses with cisplatin 75 mg/m2 based regimens every 3 weeks. The cumulative  drug  doses  ranged  from 700  to  1050  mg/m2  paclitaxel  and 450 mg/m’  cisplatin.  The demographics and baseline clinical characteristics of overall patients are shown in Table (1).

Prior to paclitaxel chemotherapy, none of the patients complained about sensorimotor symptoms. Clinical manifestations of Polyneuropathy were detected after 3 cycles of treatment.  In the first group; PNP scores were mild in 9 patients (64.3%), moderate in 4 patients (28.6%) and severe in one patient (7.1%). After 6 cycles of paclitaxel; PNP scores were mild in one patient (7.1%), moderate in 11 patients (78.6%) and severe in 2 patients (14.3%). Meanwhile 3 months after the end of the treatment; PNP scores were mild in 3 patients (21.43%), moderate in 10 patients (71.43%) and severe in one patient (7.14%).  In the second group; PNP scores after 3 cycles were mild in 3 patients (27.3%), moderate in 6 patients (54.5%) and severe in 2 patients (18.2%). After 6 cycles of combined paclitaxel-cisplatin based regimen; PNP scores were mild in one patient (9.1%), moderate in 3 patients (27.3%) and severe in 7 patients (63.6%). Meanwhile 3 months after the end of the treatment; PNP scores were moderate in 3 patients (27.3%) and severe in 8 patients (72.7%).

In paclitaxel and in paclitaxel-cisplatin based chemotherapy; the mean PNP score was 6.14±3.5 and 9.4±4.13 respectively after 3 cycles of treatment and increased significantly after 6 cycles (p =0.0001).Moreover, in paclitaxel -cisplatin based chemotherapy; the PNP score was significantly higher than that recorded with paclitaxel -based chemotherapy at the same time.

Based on the PN scores obtained on the post-treatment examination as compared with those obtained at the sixth course of chemotherapy, it was shown that the neuropathy was still present with insignificant changes in both groups (Table 2). Moreover, in either group the mean scores of the motor conduction parameters studied showed no significant changes either during the course of the treatment or three months later after cessation of treatment (Table 3). On contrast, the paclitaxel based chemotherapy showed a significant deterioration in the (a-SAPs) of both ulnar and sural nerves from the 3rd-6th cycles of the treatment. Three months later after cessation of treatment, there was also a significant deterioration in the (a-SAP) in patients treated with paclitaxel-cisplatin chemotherapy. Moreover, in paclitaxel -cisplatin based chemotherapy; the (a-SAP) was significantly lower than that recorded with paclitaxel -based chemotherapy at the same time. There was no significant change in (SCV) in either group during the course or after the end of treatment (Table 4).


Table 1. Patient’s baseline and clinical characteristics in in taxane induced neuropathy.

 

Variables

Study sample

Age ± SD

44.8±7.4 years

Sex F:M

16:9

Group I: 14 F

Group II: 2F

Tumor type

·                  Metastatic breast cancer

·                  Lung cancer (NSCLC)

 

14  patients

11  patients

Single drug doses per each one

of chemotherapy courses

 

·   Group I: received paclitaxel 175mg/m² every 21 days.

·   Group II: received paclitaxel 175mg/m² + cisplatin 75mg/m² every 21 days.

Cumulative doses

Paclitaxel in group I

 

Paclitaxel and cisplatin in groupII

 

·   9 patients (each patient received 1050mg/m² paclitaxel total)

·   4 patients (each patient received 875mg/m² paclitaxel total)

·   1 patient  ( received 700mg/m² paclitaxel total)

·   11 patients (each patient received 1050mg/m² paclitaxel total and 450mg/m² cisplatin totally during the 6 cycles

NSCLC non-small cell lung carcinoma, SD standard deviation

 

Table 2. Peripheral neuropathy score (PNP score) among the studied groups.

 

 

Group I

Group II

T-test

Mean±SD

Mean±SD

t

P-value

After 3 cycles

6.143±3.483

9.364±4.130

-2.116

0.045*

After 6 cycles

10.714±4.214

14.818±4.600

-2.322

0.029*

After 3months

9.429±3.567

15.091±5.186

-3.234

0.004*

Paired t-test

P1

0.000

0.001

 

P2

0.000

0.000

P3

0.076

0.732

Group I: patients treated by paclitaxel alone                                                            Group II: patients treated by paclitaxel cisplatin

P1: PNS after 3 cycles versus 6 cycles                                                                         P2: PNS after 3 cycles versus after 3months

P3: PNS after 6 cycles versus after 3months

SD standard deviation

* Significant difference between two groups at p<0.05

 

 

Figure 1. Peripheral neuropathy score (PNP score) among the studied groups

after 3, 6 cycles and 3 months after the end of the treatment.

Table 3. Motor conduction studies among the studied groups.

 

 

Group I

Group II

T-test

Mean±SD

Mean±SD

t

P-value

Ulnar nerve
DML (ms))

After 3 cycles

2.350±0.355

2.382±0.451

-0.198

0.845

After 6 cycles

2.293±0.377

2.427±0.398

-0.864

0.397

After 3months

2.314±0.374

2.473±0.344

-1.089

0.287

aCMAP

After 3 cycles

6.207±0.921

6.155±1.218

0.123

0.903

After 6 cycles

6.100±0.760

6.055±1.138

0.120

0.906

After 3months

6.279±0.652

6.136±0.970

0.438

0.665

MCV (m/s)

After 3 cycles

56.650±5.343

55.218±4.957

0.686

0.499

After 6 cycles

55.657±5.331

55.491±5.356

0.077

0.939

After 3months

54.993±4.946

55.418±5.557

-0.202

0.842

F-wave minimum latency (ms)

After 3 cycles

27.000±1.217

26.236±1.774

1.276

0.215

After 6 cycles

26.971±1.226

26.227±1.734

1.258

0.221

After 3months

26.943±1.253

26.327±1.579

1.088

0.288

Peroneal n
DML

After 3 cycles

4.307±0.572

3.955±0.843

1.245

0.226

After 6 cycles

3.921±0.613

3.773±0.709

0.562

0.579

After 3months

4.221±0.676

3.691±0.655

1.974

0.061

a-CAMP

After 3 cycles

4.229±1.192

4.218±1.230

0.021

0.983

After 6 cycles

4.107±1.158

4.073±1.243

0.071

0.944

After 3months

4.236±1.087

4.018±1.092

0.496

0.625

MCV (m/s)

After 3 cycles

55.550±3.792

55.709±3.178

-0.112

0.912

After 6 cycles

54.714±3.989

55.582±3.301

-0.581

0.567

After 3months

54.593±3.432

55.600±3.311

-0.740

0.467

F-wave minimum latency (ms)

After 3 cycles

49.264±2.987

48.755±2.947

0.426

0.674

After 6 cycles

49.243±2.972

48.736±2.935

0.425

0.675

After 3months

49.264±2.947

48.727±2.936

0.453

0.655

Group I: patients treated by paclitaxel alone                                                            Group II: patients treated by paclitaxel cisplatin

a Significant changes between 3cy with paired t-test.

b Significant changes between 6cy with paired t-test.

a-CMAP compound muscle action potential, DML distal motor latency, MCV motor conduction potential, SD standard deviation

 

Table 4. Sensory conduction studies among the studied groups.

 

Group I

Group II

T-test

Mean±SD

Mean±SD

t

P-value

Ulnar nerve
a-SAP (μV)

After 3 cycles

10.679±2.996

8.055±3.263

2.091

0.0478*

After 6 cycles

8.150±2.114 a

6.245±2.186 a

2.204 

0.0378*

After 3months

8.229±2.2 a

6.182±2.066 ab

2.232

0.0356*

SCV (m/s)

After 3 cycles

51.450±6.065

51.409±5.936

0.017

0.987

After 6 cycles

51.457±5.870

51.182±6.051

0.115

0.910

After 3months

51.564±5.824

50.982±5.914

0.247

0.807

Sural N
a-SAP (μV)

After 3 cycles

11.836±3.108

9.375±2.500

2.136

0.0435*

After 6 cycles

10.364±2.709a

8.264±2.105 a

2.115

0.045*

After 3months

10.543±2.700 a

7.500±1.644 ab

3.282

0.003*

SCV (m/s)

After 3 cycles

53.621±5.177

54.273±5.424

-0.306

0.762

After 6 cycles

53.564±4.873

54.027±4.672

-0.240

0.812

After 3months

53.014±5.008

53.964±4.795

-0.479

0.636

Group I: patients treated by paclitaxel alone                                                            Group II: patients treated by paclitaxel cisplatin

a Significant changes between 3cy with paired t-test.

b Significant changes between 6cy with paired t-test.

a-SAP sensory action potentials, SCV sensory conduction velocity, SD standard deviation

* Significant difference between two groups at p<0.05

 


DISCUSSION

 

Over the past years, several new anti-neoplastic agents demonstrated their efficacy against a broad spectrum of solid malignancies. However, the cytotoxic usefulness of these drugs is compromised by a wide range of side effects; with the fast-dividing cells of the body to bear the main brunt of these toxicities14. Chemotherapy-induced neurotoxicity is the main non-hematological dose-limiting side effect. This condition may pose challenge for the clinician to diagnose and manage11. Therefore, this work was conducted to study the clinical and electrophysiological findings of paclitaxel –induced peripheral neuropathy in cancer patients. We examined the patients clinically and electro physiologically after 3 and 6 cycles of chemotherapy, then patients were followed up to 3 months after the end of the therapy. The evaluation of nerve function was based on symptoms, clinical signs, and electrophysiological findings, summarized by means of a modified PNP score, previously applied in studies of toxic neuropathies9,15,16.

In this study, 73.5% of patients developed clinical and electrophysiological manifestations of predominantly sensory polyneuropathy after 3 cycles of treatment. Our results are in agreement with that previously described in the case of cisplatin- or paclitaxel-induced PN17,18. The precise mechanisms underlying neurotoxicity are not yet known and the primary target of taxane-induced neuropathy is controversial. In some clinical taxane-induced neuropathy cases, dysfunctional microtubules in axons, Schwann cells and dorsal root ganglia were observed. So, toxic neuropathies may have three presumed sites of cellular involvement including; axonopathy, myelinopathy, and ganglionopathy.11, 18. Prior to paclitaxel chemotherapy, none of the patients complained about sensorimotor symptoms. In both groups, the severity of peripheral neuropathy increased significantly from the 3 to 6 cycles of the treatment. The severity was ranged from mild to moderate in the majority of the patients. 

In  comparison  to  paclitaxel  monotherapy,  the  combination  paclitaxel/cisplatin  appears  to  result  in  enhanced  intensity of neurotoxicity.  Several studies have suggested that in parallel to the synergistic beneficial effects of taxanes with platenium compounds, such as cisplatin, this combination may also, have additive effects in producing peripheral neuropathy15

In paclitaxel as well as paclitaxel-cisplatin based chemotherapy; mean scores of the motor conduction parameters studied showed no significant changes either during the course of the treatment or three months later after cessation of treatment. Also, F-wave latency delay that would suggest demyelination indirectly implying axonal rather than myelin–Schwann cell damage, was also absent. Motor neuropathy of paclitaxel therapy is not well documented as reported by Berger et al.17. This  is  probably  due  to  the  fact  that  only  mild  motor  weakness,  especially  mild  weakness  of  the  toe  extensor  muscles,  has  been  observed and  these  alterations  rarely  affect  motor  functions. Our results are supported by other previous studies of paclitaxel monotherapy 19, 20 as well as paclitaxel/cisplatin combination therapy10,15. In  contrast, Berger et al.17, found that their patients who treated with paclitaxel-cisplatin based chemotherapy  had reduced  peroneal  evoked  amplitudes,  prolonged  distal  latencies  and  slowing  of  motor  nerve  conduction  velocities suggest  that  motor  nerve  involvement  is  more  severe. This motor neuropathy was dependent on the cumulative doses of the drugs which was higher than that used in our study. On the other hand, electrophysiological longitudinal examinations confirm the diagnosis of an axonal, predominately sensory neuropathy, as the sensory nerve conduction studies showed significant decrease of a-SAPs, with preservation of SCV in both groups along the course of the treatment. These results are in agreement with that previously described in the case of cisplatin- or paclitaxel-induced PN10,18,21.

As concerning the course of PN after the cessation of treatment, we have found no significant reversibility in PNP scores. On the contrary, further progression of neuropathy after the discontinuation of chemotherapy, as particularly demonstrated by the sensory conduction abnormalities, was evident in group II. One could postulate that this event should be attributed to cisplatin administration, since this phenomenon, called coasting, is characteristic of cisplatin therapy and it is resulting from its capacity to accumulate in dorsal root ganglia for a long time19. On the other hand, Rowinsky et al. reported that the reversibility of CIPN depends on the degree of neuropathy as mild neuropathy usually is reversible shortly after stopping paclitaxel therapy, severe neuropathy may persist for several months22. However, unlike previously reported data 23, newly appeared evidence of PN was not observed after cessation of therapy.

Limitations in the study design are the relatively small sample size studied, and the follow-up evaluation of 3 months after the suspension of chemotherapy might be not long enough.

From a clinical point of view, the results of our study indicate that patients who would receive a paclitaxel-based regimen should be screened for evidence of CIPN, at least along with the administration of the third chemotherapy course. Physicians should be aware that with the administration of combined paclitaxel and cisplatin, an increased severity of PN should be anticipated and therefore, the administration of neuroprotective agents should also be considered. The identification of a specific profile of paclitaxel-induced PN, as regarding the type, severity and course, would be particularly useful for clinical studies that attempt to identify an ideal neuroprotective agent against paclitaxel- and/or cisplatin-induced PN. Such an ideal candidate should clearly demonstrate neuroprotection and be safe for patients, without reducing the efficacy of chemotherapeutic agents on the tumors 6. In conclusion, our results indicate that patients treated with either paclitaxel alone or in combination with cisplatin based regimen at full dose intensities would manifest an axonal, predominately sensory PN, of mild to moderate severity. Combination of taxane and cisplatin increases the severity of PN than taxane alone. Persistence of PN for at least 3 months after the discontinuation of paclitaxel-cisplatin based chemotherapy also should be expected.

 

[Disclosure: Authors report no conflict of interest]

 

REFERENCES

 

1.        Rowinsky EK, Donehower RC. Drug therapy: Paclitaxel (Taxol). N Eng J Med. 1995; 332: 1004-14.

2.        Tang SC. Strategies to decrease taxanes toxicities in the adjuvant treatment of early breast cancer. Cancer Invest. 2009; 27(2): 206-14.

3.        Rowinsky EK, Cazenave LA, Donehower R. Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst. 1990; 82: 1247-1259.

4.        Von Minckwitz G, Costa SD,  Raab G,  Merkle E, Jackisch C, Gademann G, et al. Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as periopaerative therapy in patient with operable carcinoma of the breast: a randomized controlled open phase IIb study. J Clin Oncol. 2001; 19: 3506-15.

5.        Cella D, Peterman A, Hudgens S, Webster K, Socinski M. Measuring the side effects of taxane therapy in oncology. Cancer. 200 3; 98: 822-31.

6.        Baker J, Ajani J, Scotte F., Winther D, Martin M, Aapro MS, et al. Docetaxel-related side effects and their management. Eur J of Oncol Nurs. 2008; 13: 49-59.

7.        Capri G, Munzone E, Tarenzi E, Fulfaro F, Gianni L, Caraceni A, et al. Optic nerve disturbances: a new form of paclitaxel neurotoxicity. J Nat Cancer Inst. 1994; 86 (14): 1099-101.

8.        Argyriou AA, Polychronopoulos P, Koutras A, Iconomou G, Iconomou A, Kalofonos HP, et al. Peripheral neuropathy induced by administration of cisplatin- and paclitaxel-based chemotherapy. Could it be predicted? Support Care Cancer. 2005; 13: 647–51.

9.        Argyriou A, Chroni E, Koutras A, Ellul J, Papapetropoulos S, Katsoulas G, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: A randomized controlled trial.   Neurology. 2005; 64: 26-31.

10.     Argyriou AA, Polychronopoulos P, Koutras A, Xiros N, Petsas T, Argyriou K, et al. Clinical and electrophysiological features of peripheral neuropathy induced by administration of Cisplatin plus Paclitaxel-based chemotherapy. Euro J Cancer Care. 2007; 16(3): 231-7.

11.     Argyriou AA, Koltzenburg M, Polychronopoulos P, Papapetropoulos S, Kalofonos HP. Peripheral nerve damage associated with administration of taxanes in patient with cancer. Critical Review in Oncology/Hematology. 2008; 66: 218-28.

12.     Dyck PJ, Thomas PK.  Peripheral neuropathy, 3rd ed., Volume 2. Philadelphia, PA: WB Saunders; 1993. p.1310-7.

13.     Kimura J. Electrodiagnosis in diseases of nerve and muscle, principles and practice (3rd ed.). New York: Oxford University Press; 2001. p 91-166.

14.     Carr C, Julia N, Wigmore T. The side effects of chemotherapeutic agents: Curr Anesth & Critic Care. 2008; 19: 70-79.

15.     Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR. Peripheral neuropathy from Taxol and Cisplatin chemotherapy: clinical and electrophysiological studies. Ann Neurol. 1994; 35: 304-311.

16.     Chaudhry V, Cornblath DR, Corse A, Freimer M, Simmons-O'Brien E, Vogelsang G. Thalidomide induced neuropathy. Neurology. 2002; 59: 1872-1875.

17.     Berger T, Malayeri R, Doppelbauer A, Krajnik G, Huber H, Auff E, et al. Neurological Monitoring of Neurotoxicity Induced by Paclitaxel-cisplatin Chemotherapy. Eur J  Cancer. 1997; 33 (9): 1393-9. 

18.     Quasthoff S,  Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol. 2002; 249(1): 9-17.

19.     Sahenk Z, Barohn R, New P, Mendell JR.  Taxo1 neuropathy. Arch Neurol. 1994, 51: 726-9.

20.     Cavaletti G, Bogliun G, Marzorati L, Zincone A, Marzola M, Colombo N, et al.  Peripheral neurotoxicity of Taxol in patients previously treated with cisplatin. Cancer. 1995, 75, 1141-50.

21.     Hamers FP, Gispen WH, Neijt JP. Neurotoxic side effects of cisplatin. Eur J Neurol. 1991; 27, 372-6.

22.     Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC.  Clinical toxicities encountered by paclitaxel (Taxol). Semin Oncol. 1993; 20 (Suppl. 3): 1–15.

23.     Grunberg SM, Sonka S, Stevenson LL, Muggia FM. Progressive paresthesias after cessation of therapy with very high dose cisplatin. Cancer Chemother Pharmacol. 1989; 25: 62-4.


 

 

 

الملخص العربى

 

 

يعد اعتلال الأعصاب الطرفية عرض جانبي متكرر ومصاحب للعلاج الكيماوي وهى تحد من استعمال العلاج بالجرعة التى يتحقق معها أفضل النتائج حيث يؤدي تلف الأعصاب الطرفية إلى إنقاص أو انقطاع جرعة العلاج تماما. ينتمى عقار الباكليتاكسل إلى مجموعة التاكسين والتى تسبب تلف الأعصاب الطرفية عن طريق بلمرة التوبيولين مما يؤدى إلى منع الانقسام الطبيعى للخلية كما يؤثر على الخلية العصبية. وقد صمم هدا البحث لدراسة التغيرات الإكلينيكية الإلكتروفسيولوجية فى مرضى السرطان الذين يتناولون عقار الباكليتاكسيل. 

وقد شمل البحث 34 مريضا بالسرطان كانوا يعالجون إما بعقار الباكليتاكسيل بمفرده أو بإضافته إلى عقار السيسبلاتين فى 6 دورات علاجية وعلى هذا قسم المرضى إلى مجموعتين: الأولى وقد شملت مرضى سرطان الثدى فى مرحلة الانتشار وكانوا يعالجون بعقار الباكليتاكسيل بمفرده و الثانية وشملت مرضى سرطان الرئة وكانوا يعالجون بعقار الباكليتاكسيل مع عقار السيسبلاتين. ولدراسة اعتلال الأعصاب الطرفية لدى هؤلاء المرضى  تم فحصهم إكلينيكيا وبالاستعانة برسم العصب الكهربائي وذلك بعد 3 و 6 دورات علاجية من هده الأدوية وتم إعادة الفحص للمرة الثالثة بعد 3 أشهر من توقف العلاج.

وقد تبين من هذه الدراسة أن كلا من المرضى الذين كانوا يعالجون بعقار الباكليتاكسيل بمفرده أو بإضافته إلى عقار السيسبلاتين ظهر لديهم أعراض إكلينيكية وإلكتروفسيولوجية لاعتلال الأعصاب الطرفية وكانت تؤثر بالأساس على أعصاب الإحساس أكثر من أعصاب الحركة. وأنه كلما زاد عدد الدورات والجرعة المتراكمة لعقار الباكليتاكسيل كان هناك تزايد ذا دلالة إحصائية فى شدة اعتلال الأعصاب الطرفية.

وقد وجد أيضا أن هذا الاعتلال يكون أشد عند إضافة عقار السيسبلاتين إلى الباكليتاكسيل. كما أظهرت الدراسة أن هذا الاعتلال لم يطرأ عليه تحسن إكلينيكي ذا دلالة إحصائية بعد توقف الدواء وقد استمر هذا الاعتلال بالتدهور إلكتروفسيولجيا فى المجموعة الثانية بعد توقف الدواء.



2008 � Copyright The Egyptian Journal of Neurology,
Psychiatry and Neurosurgery. All rights reserved.

Powered By DOT IT