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Gabapentin Monotherapy for the Treatment of Chemotherapy-Induced Neuropathic Pain: A Pilot Study

Nicolas Tsavaris MD, Petros Kopterides MD, Christos Kosmas MD, Athina Efthymiou MD, Hlias Skopelitis MD, Antonios Dimitrakopoulos MD, Eyterpi Pagouni MD, Dimitrios Pikazis MD, Panagiotis-Vasilis Zis MD, Christos Koufos MD
DOI: http://dx.doi.org/10.1111/j.1526-4637.2007.00325.x 1209-1216 First published online: 1 November 2008

ABSTRACT

Objective. This study was conducted to investigate the efficacy and safety of gabapentin monotherapy in the management of chemotherapy-induced neuropathic pain.

Patients. Seventy-five cancer patients who had previously received chemotherapy, and had experienced at least one symptom of neuropathic pain were included in the intervention group. They received a fixed low-dose of gabapentin (800 mg/day). The control group consisted of 35 cancer patients with similar treatment history and symptomatology, who refused treatment with gabapentin and, therefore, received a fixed-dose combination of naproxen and codeine/paracetamol.

Outcome Measures. Patients were grouped in three categories according to the severity of their neuropathic symptoms at baseline: mild, moderate, and severe. Analgesic efficacy of the study drug was assessed by means of a patient-answered questionnaire. Four stages of analgesic response were established: complete, partial, minor, and no response.

Results. All patients completed the study and were evaluable. In the intervention arm, gabapentin led to a complete response in 25.3% of patients (19/75), partial response in 44% (33/75), minor response in 25.3% (19/75), and no response in 5.3% (4/75). The response to gabapentin correlated with the severity of the underlying neurotoxicity. Approximately 25% of patients receiving gabapentin experienced mild somnolence, but none discontinued it. In the control group, none experienced complete response (0/35), while partial, minor, and no response were observed in 5.7% (2/35), 45.7% (16/35), and 48.6% (17/35), respectively. Compared with the control group, gabapentin therapy led to a statistically significant better response in patients of each baseline neurotoxicity group.

Conclusions. Gabapentin monotherapy seems to be well tolerated and useful for the management of chemotherapy-induced neuropathic pain.

  • Chemotherapy
  • Gabapentin
  • Neuropathic Pain
  • Neuropathy
  • Neurotoxicity
  • Palliative Care

Introduction

Neuropathic pain is a common and significant source of morbidity in cancer patients [1]. It is caused by a variety of etiologies, such as tumor-related nerve compression, radiation-induced nerve injury, and paraneoplastic syndromes [2], or directly, as a common side effect of chemotherapeutic agents. Its type and severity depend on the drugs and doses used (single and cumulative), and the coexistence of diseases with neurotoxic potential, such as diabetes mellitus [3].

Neurotoxicity can severely compromise the quality of life. More importantly, it can be a reason for dose reduction or even discontinuation of a potentially curative chemotherapeutic regimen [3,4]. The cytostatic drugs, for which neurotoxicity is a major side effect, are the platinum compounds (cisplatin, carboplatin, oxaliplatin), vinca alkaloids (vincristine, vinorelbine, vindesine), and taxanes (paclitaxel, docetaxel) [5].

Clinical experience dictates that chemotherapy-induced peripheral neuropathy (CIPN) is a difficult problem to manage. A number of agents (nerve growth factor, insulin-like growth factor I, amifostine) with neuroprotective potential have been developed, but none can be currently recommended for wide use in daily clinical practice [4,6]. As there is no etiologic treatment for CIPN, our therapeutic approach is focused mainly on the alleviation of the neuropathic symptoms.

Gabapentin is an anticonvulsant, structurally related to gamma-aminobutyric acid (GABA), that has shown analgesic activity in several experimental [7] and clinical models of chronic neuropathic pain, such as postherpetic neuralgia [8,9], diabetic neuropathy [10], HIV-associated sensory neuropathy [11], and postamputation phantom-limb pain [12]. Gabapentin has also been shown to be a useful adjuvant to opioid analgesia for neuropathic cancer pain [13,14], but little is known about its use as a monotherapy in the setting of CIPN.

Thus, we performed a prospective, nonrandomised, pilot study in order to investigate the efficacy and safety of low-dose gabapentin in the treatment of patients with chemotherapy-induced neuropathic pain.

Methods

Inclusion and Exclusion Criteria

Cancer patients were eligible for inclusion in the study if they were younger than 70 years, had a Karnofsky performance status ≥80, and experienced at least one of the following neuropathic symptoms: cutaneous hyperesthesias, and/or allodynia, and/or burning, and/or shooting, and/or lancinating pain. Patients with a history of diabetes mellitus, heart failure, renal insufficiency (baseline creatinine higher than 1.4 mg/dL), cirrhosis, psychotic disorders, and use of tranquillizers or alcohol (more than two glasses of wine per day) were excluded. The use of opiates, non-steroidal anti-inflammatory agents (NSAIDs), and tricyclic antidepressants (TCAs) was also an exclusion criterion.

Patients

Seventy-five patients with a histologically confirmed malignancy entered the intervention arm of the study. The study population consisted of three patients with breast cancer who received second-line chemotherapy with docetaxel and epirubicin, eight patients with small-cell lung cancer who received paclitaxel and carboplatin, twelve patients with nonsmall-cell lung cancer (NSCLC) who received paclitaxel, ifosfamide, and cisplatin, six patients with NSCLC who received docetaxel and carboplatin, eight patients with NSCLC who received second-line chemotherapy with vinorelbin and gemcitabine, five patients with ovarian cancer who received paclitaxel and carboplatin, seven patients with ovarian cancer who received second-line therapy with paclitaxel, ifosfamide, and cisplatin, six patients with head and neck cancer who received second-line therapy with paclitaxel, ifosfamide, and cisplatin, 12 patients with colorectal cancer who received second-line therapy with oxaliplatin, leucovorin, and 5-fluorouracil, three patients with sarcomas who received doxorubicin, ifosfamide, and cisplatin, and five patients with germ-cell tumors who received second-line chemotherapy with paclitaxel, ifosfamide, and cisplatin.

The control group consisted of 35 cancer patients (22 men; 62.8%), with a median age of 66 years (range: 21–70), and similar underlying malignancies, treatment history, and symptomatology with the study group that declined participation in the study for personal reasons but agreed to provide information about their pain experience. They received a fixed-dose combination of codeine/paracetamol (30/500 mg) thrice a day and naproxen (250 mg) twice a day.

Tables 1 and 2 summarize the demographic characteristics of the patients in the intervention and control groups, respectively, while Table 3 depicts the administered chemotherapy regimens.

View this table:
Table 1

Demographics and baseline characteristics of patients treated with gabapentin

CancerGenderMedian Age (years)KPSBaseline Neurotoxicity
MF9080MildModerateSevere
Breast 0 357 (48–64)21 0 21
SCLC 7 168 (57–70)35 1 43
NSCLC23 365 (58–70)91711123
Ovarian 01264 (52–70)210 3 81
Head and neck 6 068 (65–70)24 1 41
Colorectal 7 563 (55–68)66 2 82
Sarcomas 1 246 (35–54)03 1 20
Germ-cell 5 026 (23–31)32 0 23
Total492657 (23–70)2748194214
  • SCLC = small-cell lung cancer; NSCLC = nonsmall-cell lung cancer; M = male; F = female; KPS = Karnofsky performance status.

View this table:
Table 2

Demographics and baseline characteristics of the control group patients

CancerGenderMedian Age (years)KPSBaseline Neurotoxicity
MF9080MildModerateSevere
Breast 0 160 1 01 00
SCLC 2 063 (59–67) 2 00 20
NSCLC10 264 (58–69)10 23 81
Ovarian 0 764 (54–70) 2 51 60
Head and neck 3 066 (60–70) 1 20 21
Colorectal 3 364 (59–68) 5 10 33
Sarcomas 1 054 0 10 10
Germ-cell 3 026 (21–31) 1 20 21
Total221366 (21–70)22135246
  • SCLC = small-cell lung cancer; NSCLC = nonsmall-cell lung cancer; M = male; F = female; KPS = Karnofsky performance status.

View this table:
Table 3

Chemotherapy regimens

Type of CancerSchedule
BreastDocetaxel 100 mg/m2 and epirubicin 100 mg/m2, every 21 days
NSCLCPaclitaxel 220 mg/m2, ifosfamide 5 g/m2 and cisplatin 100 mg/m2, every 21 days
NSCLCDocetaxel 100 mg/m2 and carboplatin 6-AUC, every 21 days
NSCLCVinorelbin 30 mg/m2, gemcitabine 600 mg/m2, days land 8, every 21 days
OvarianPaclitaxel 220 mg/m2, carboplatin 6-AUC, every 21 days
OvarianPaclitaxel 220 mg/m2, ifosfamide 5 g/m2 and cisplatin 100 mg/m2, every 21 days
Head and neckPaclitaxel 220 mg/m2, ifosfamide 5 g/m2 and cisplatin 100 mg/m2, every 21 days
ColorectalOxaliplatin 60 mg/m2, leucovorin 100 mg/m2 and 5-fluorouracil 500 mg/m2, every 21 days
SarcomasIfosfamide 5 g/m2 and cisplatin 100 mg/m2, alternating with doxorubicin 70 mg/m2, every 21 days
Germ-cellPaclitaxel 220 mg/m2, ifosfamide 5 g/m2 and cisplatin 100 mg/m2, every 21 days
  • NSCLC = nonsmall-cell lung cancer.

The study patients were grouped in three categories according to the severity of their neuropathic pain symptoms, before the administration of gabapentin: 1) severe, if neuropathic symptoms had a major impact on their daily life activities; 2) moderate, if symptoms were troublesome, but did not interfere with their quality of life; and 3) mild, if symptoms were slightly perceptible.

Study Design

After enrollment in the study, patients underwent a complete physical examination (including a thorough neurologic evaluation), and a basic laboratory work-up, including a complete blood count and a comprehensive metabolic panel. Side effects were monitored and laboratory work-up was repeated before the administration of each cycle. All patients were followed closely for the development of neuropathic pain. When neuropathic symptoms developed during the study period, the dosage of the administered cytostatic drugs was kept constant and gabapentin therapy was initiated; if these symptoms worsened during subsequent cycles, neurotoxic chemotherapy was administered at lower doses or discontinued.

The study protocol was reviewed and approved by the ethics committees of the participating hospitals. All patients gave written informed consent.

Drug Administration

After enrollment in the study, patients received a fixed low-dose of gabapentin (800 mg/day, at bedtime), until withdrawal from the study or complete disappearance of the neuropathic symptoms.

Outcome Measures

The primary efficacy end-point for our trial was the analgesic response to the study medication as judged from a patient-answered questionnaire. We established four stages of analgesic response:

Complete Response

There was a complete disappearance of neuropathic symptoms; chemotherapy was continued at the same doses concurrently with gabapentin therapy.

Partial Response

There was a significant improvement of the symptoms; chemotherapy was continued at a dose approximately 25% lower concurrently with gabapentin therapy.

Minor Response

There was a small decrease of symptoms' intensity; chemotherapy was administered at a dose approximately 25% lower, and gabapentin was continued. If symptoms worsened, chemotherapy was modified, but therapy with gabapentin was continued.

No Response

There was no response to a 3 weeks' course of gabapentin; after this period, gabapentin was discontinued, and chemotherapy was modified or discontinued.

Evaluation of Other Parameters Except Neurotoxicity

Patients' completed diaries were also used for the monitoring of the gabapentin treatment side effects.

Statistical Evaluation

All analyses were conducted with the use of the chi-squared test. No assumptions concerning the direction of the possible associations were made. A P value <0.05 was considered statistically significant. Data were analyzed using spss for Windows version 12.0 (SPSS Inc., Chicago, IL).

Results

Analgesic Response

All patients completed the study and were evaluable. Overall, gabapentin therapy led to a complete response in 25.3% of patients (19/75), partial response in 44% (33/75), minor response in 25.3% (19/75), and no response in 5.3% (4/75). Table 4 shows in detail the efficacy of gabapentin in the various subgroups of cancer patients.

View this table:
Table 4

Analgesic response to therapy with gabapentin

Type of CancerChemotherapyBaseline NeurotoxicityResponse
MildModerateSevereCRPRMRNR
BreastTr + Epi 2 1 0 2 1 00
SCLCTl + JM8 1 3 4 4 4 00
NSCLCTl + Ifo + CDDP 5 5 2 2 7 21
NSCLCTr + JM8 1 4 1 2 2 11
NSCLCVin + Ge 3 5 0 2 5 10
OvarianTl + JM8 2 3 0 2 2 10
OvarianTl + Ifo + CDDP 1 5 1 1 2 40
Head and neckTl + Ifo + CDDP 1 4 1 0 2 31
ColorectalOxP + lV + 5-FU 2 8 2 2 5 50
SarcomaDox + Ifo + CDDP 1 2 0 1 2 00
Germ-cellTl + Ifo + CDDP 0 2 3 1 1 21
Total1942141933194
  • Epi = epirubicin; Tr = docetaxel; Tl = paclitaxel; Ifo = ifosfamide; Vin = vinorelbin; Ge = gemcitabine; CDDP = cisplatin; JM8 = carboplatin; OxP = oxaliplatin; LV = leucovorin; 5-FU = 5-fluorouracil; Dox = doxorubicin; CR = complete response; PR = partial response; MR = minor response; NR = no response.

Thirteen of the 19 patients (68.4%) with mild neuropathic pain had a complete response; in addition, three patients (16%) had a partial response, two (11%) had a minor response, and one (5%) showed no response at all. Six of the 42 (14.2%) patients with moderate neuropathic pain presented complete response, 25 (60%) patients partial, 10 (24%) minor response, and one (2%) no response at all. Finally, from the 14 patients with serious baseline neuropathic pain, two (14%) did not show any response to treatment, while seven (50%) showed a minor, and five (35%) a partial response. Interestingly, no patient with severe baseline neuropathic pain obtained a complete response.

As shown in Table 5, for both patients with mild and moderate pain symptoms at baseline, the use of gabapentin was associated with a significantly improved and clinically meaningful (complete and partial) analgesic response (94.1% vs 17.6%; P < 0.001 for mild baseline neuropathic symptoms and 72% vs 25.5%; P < 0.0001 for moderate symptoms). In addition, patients with mild baseline neurotoxicity achieved a complete response more often than the other two groups (68.4% vs 14.2% for moderate symptoms vs 0% for severe symptoms; P < 0.01 for all comparisons). These results suggest that the response to gabapentin monotherapy depends on the severity of the baseline neuropathic pain.

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Table 5

Analgesic response to gabapentin treatment according to the degree of baseline neuropathic pain

Baseline Neuropathic PainAnalgesic Response to Gabapentin
CR + PR (%)MR + NR (%)P value
Mild (N = 19)13 + 3 (94.1) 2 + 1 (17.6)<0.001
Moderate (N = 42) 6 + 25 (72.0)10 + 1 (25.5)<0.0001
Severe (N = 14) 0 + 5 (33.3) 7 + 2 (60.0)>0.15
  • CR = complete response; PR = partial response; MR = minor response; NR = no response.

Four patients with no response stopped therapy after 3 weeks' administration of gabapentin; in that setting, chemotherapy was modified or discontinued. All 19 patients with minor response derived benefit from gabapentin therapy for a maximum of 6–9 weeks; this period included a 3 weeks' treatment course after lack of further response. Thereafter, some of them (11 patients) stopped chemotherapy because of a favorable response to it, and the rest (eight patients) continued with modification of the chemotherapy doses. Thirty-one patients showed a partial response to gabapentin treatment that lasted for 12–15 weeks (including a 3 weeks' administration beyond the point of further response). All of them managed to complete their chemotherapy cycles. Finally, patients with a complete response continued gabapentin for 3 weeks and then discontinued it, as they had no pain symptoms.

The evolution of neuropathic pain in the patients of the control group is shown in Table 6. It is noteworthy that none (0/35) experienced complete response, while partial, minor, and no response were observed in 5.7% (2/35), 45.7% (16/35), and 48.6% of the patients (17/35), respectively. Table 7 shows in detail the evolution of neuropathic pain according to its intensity at baseline and its treatment or not with gabapentin. For each one of the three groups of baseline neuropathic pain (data shown in Table 8), a greater percentage of patients treated with gabapentin achieved the composite outcome of complete/partial analgesic response instead of minor/no response (for example, 94.1% vs 20% for minor neuropathic pain at baseline; P = 0.002).

View this table:
Table 6

Analgesic response to therapy in the control group

Type of CancerChemotherapyBaseline NeurotoxicityResponse
MildModerateSevereCRPRMRNR
BreastTr + Epi1 0000 1 0
SCLCTl + JM80 2000 2 0
NSCLCTl + Ifo + CDDP2 3101 2 3
NSCLCTr + JM81 2000 2 1
NSCLCVin + Ge1 2000 1 2
OvarianTl + JM80 3000 2 1
OvarianTl + Ifo + CDDP1 3000 2 2
Head and neckTl + Ifo + CDDP0 2100 1 2
ColorectalOxP + lV + 5-FU0 3300 2 4
SarcomaDox + Ifo + CDDP0 1000 0 1
Germ-cellTl + Ifo + CDDP0 2101 1 1
Total6236021617
  • Epi = epirubicin; Tr = docetaxel; Tl = paclitaxel; Ifo = ifosfamide; Vin = vinorelbin; Ge = gemcitabine; CDDP = cisplatin; JM8 = carboplatin; OxP = oxaliplatin; LV = leucovorin; 5-FU = 5-fluorouracil; Dox = doxorubicin; CR = complete response; PR = partial response; MR = minor response; NR = no response.

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Table 7

Analgesic response in the control group according to the degree of baseline neuropathic pain neurotoxicity

Baseline Neuropathic PainAnalgesic Response
CR + PR (%)MR + NR (%)P value
Mild (N = 5)0 + 1 (20.0)4 + 0 (80.0) 0.09
Moderate (N = 24)0 + 1 (4.0)8 + 15 (95.8)<0.00001
Severe (N = 6)0 (0)3 + 3 (100.0) 0.006
  • CR = complete response; PR = partial response; MR = minor response; NR = no response.

View this table:
Table 8

Comparison of the analgesic response between the examined groups according to the degree of baseline neuropathic pain

Baseline Neuropathic PainAnalgesic Response
CR + PRMR + NR
GG N (%)CG N (%)P valueGG N (%)CG N (%)P value
Mild0 + 1 (20.0)13 + 3 (94.1) 0.0024 + 0 (80.0) 2 + 1 (17.6) 0.008
Moderate0 + 1 (4.0) 6 + 25 (72.0)<0.000018 + 15 (96.0)10 + 1 (25.5)<0.00001
Severe0 (0) 0 + 5 (33.3) 0.0063 + 3 (100.0) 7 + 2 (60.0) 0.04
  • CR = complete response; PR = partial response; MR = minor response; NR = no response; CG = control group; GG = gabapentin group; N = number of patients.

Drug Side Effects

Fifteen patients (25%) in the gabapentin group experienced drowsiness and mild somnolence, but none discontinued the study medication because of intolerance.

Discussion

Our results show that a fixed low-dose of gabapentin can be of value in the management of chemotherapy-induced neuropathic pain. An important finding is that its effectiveness is maximized when it is used in patients without severe baseline neuropathic pain, implying that it should be considered early, rather than late, in the therapeutic algorithms. Specifically, while approximately 85% of patients with mild painsymptoms achieve complete or partial response, the response rate drops to approximately 35% when the baseline symptoms are severe. We also confirm that gabapentin is an extremely safe and well-tolerated medication as no patient discontinued it because of side effects.

Progress in cancer research is illustrated by the discovery and development of novel chemotherapeutic agents; however, the benefits of these agents are frequently offset by their side effects. Of the numerous adverse effects associated with the use of antineoplastic drugs, peripheral neuropathy is one of the most frequent, debilitating, and, not uncommonly, the major dose-limiting side effect. In fact, nowadays, the successful and aggressive treatment of chemotherapy-induced nausea and vomiting, and the discovery of bone marrow stimulants, such as erythropoietin and granulocyte colony-stimulating factor, that ameliorate bone marrow toxicity, have allowed the use of combinations of antineoplastic drugs. These combinations lead to improved survival rates (e.g., the combination of cisplatin and paclitaxel in the treatment of ovarian cancer), but, at the expense of synergistic neurotoxic potential [15].

Several agents have been developed with the aim of ameliorating the neurotoxicity of antitumor drugs. These include growth factors, such as nerve growth factor [16], and insulin-like growth factor [17], antioxidants, such as amifostine [18,19], and glutathione [20,21], corticosteroids or ACTH-like substances [22,23], calcium-channel blockers [24], glutamine [25], venlafaxine [26], and topiramate [26]. Unfortunately, the available clinical data are either conflicting or insufficient to support the routine use of these agents in the prevention or treatment of chemotherapy-induced neurotoxicity. Therefore, the therapeutic approach is focused on the symptomatic treatment of paresthesias and pain with opiates in combination with other medications, such as TCAs [27].

Gabapentin is an alkylated analog of GABA with a mechanism of action that has not yet been fully elucidated, but it is known to modulate voltage-dependent alpha2-delta calcium-channel subunits [28], an important mechanism of neuropathic pain [29]. It has an established track record in the management of postherpetic neuralgia [8,9] and painful diabetic neuropathy [10], and its use has begun to be explored in cancer patients.

Caraceni et al. [13] administered gabapentin as an “add-on” therapy for at least 1 week to 22 cancer patients with neuropathic pain partially responsive to opiate treatment and found that global pain, burning pain, shooting pain episodes, and allodynia decreased in intensity and frequency. Overall, 20 patients (90%) judged the drug “efficacious” in relieving their symptoms. Chandler and Williams [14] carried out a retrospective review of the case notes of 20 patients who had been prescribed gabapentin and found that only nine (45%) reported a significant improvement in their pain following administration of gabapentin, while six patients (30%) discontinued the medication due to severe side effects.

Despite the absence of solid evidence, gabapentin has been gradually incorporated in the therapeutic schemes of neuropathic cancer pain. Oneschuk and al-Shahri [30] performed a retrospective medical chart review of 45 cancer patients suffering from neuropathic pain with the aim to reveal the “real-life” therapeutic approach; they found that 22 patients (49%) had received gabapentin as an adjuvant analgesic at a cumulative daily dose of 100–3,000 mg (median: 900 mg). The medication had been stopped in 10 patients (46%). Interestingly, the change in pain scores was not significantly different in those who continued gabapentin compared with those who discontinued it.

Recently, Caracani et al. [31] performed the first multicenter, randomized, double-blind, placebo-controlled, parallel-design trial of gabapentin “added-on” an opioid-based regimen and found a significant difference of average pain intensity between the gabapentin and the placebo group. A closer analysis of the data reveals that, from the 79 patients receiving the study medication on day 1, only 58 patients (76%) completed the 10-day protocol. Seven patients (8.8%) were withdrawn because of increased opioid requirements for insufficient pain relief and six (7.6%) due to adverse events. Even though this study brought the clinical research on gabapentin and neuropathic cancer pain to the era of evidence-based medicine, its authors carefully concluded that “it has a limited role as adjuvant to opioids for neuropathic cancer pain” and called for “better study design, and more efficacious drugs.”

Our study results seem to be in accordance with that of Caracani et al. [13], as we found a clinically significant response rate of approximately 75%. The lack of side effects can be attributed to the low-dose (800 mg) used in our study compared with the more than 900-mg dose used in previous uncontrolled studies [13,14], or the 1,800-mg dose used in the recent placebo-controlled study [31].

Our study has several limitations; the most significant are the lack of blinding and a placebo-controlled arm. However, the group of patients with similar characteristics that refused gabapentin and received a regimen of opioid/paracetamol/NSAID served as a real-life, albeit less than ideal, control. Another limitation of our study is that, in contrast with previous studies, no opioid use was allowed in the intervention group, and a rather low dose (800 mg) of gabapentin was administered at bedtime (in order to minimize daytime somnolence and according to usual clinical practice in our country), despite the fact that doses up to 3,600 mg have been used in split doses throughout the day. Our intention was to conduct a “proof-of-principle” trial, as we mainly attempted to explore the safety and efficacy of low-dose gabapentin as a “stand-alone,” and not “add-on” medication, in the setting of chemotherapy-induced neuropathic pain. However, we currently evaluate the safety and efficacy of higher daily doses administered throughout the day. In addition, there was no quantitative assessment of the treatment response (e.g., with the use of a numerical scale) and no formal evaluation of the underlying neuropathy; however, it is known that, even when neuropathy is present, evaluation of its severity may yield varying results owing to the different rating scales used to classify it [4,32]. Moreover, the usually performed tests (nerve conduction studies and electromyography) may be normal in the early stages of neuropathy.

Conclusions

Our study shows that gabapentin, administered at a low-dose, may be a useful drug for the management of chemotherapy-induced neuropathic pain. If our finding, that its efficacy depends on the degree of underlying neurotoxicity, is confirmed in larger studies, it would be interesting to explore the possibility that prophylactic coadministration with potentially neurotoxic chemotherapy regimens may attenuate the severity of neurotoxicity. The prophylactic administration of potent antiemetic regimens with highly emetogenic chemotherapy regimens may serve as a useful example. Further prospective randomized studies are warranted to address this question.

References

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