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Use of Gabapentin in the Prevention of Taxane-Induced Arthralgias and Myalgias

University of California San Francisco and the San Francisco Veterans Affairs Medical Center, San Francisco, CA

To the Editor:

Taxanes (paclitaxel and docetaxel) can induce disabling but transient arthralgias and myalgias in up to 75% of patients; these events typically occur 1 to 3 days after taxane therapy and may significantly affect patients' quality of life for several days.¹ Small studies, predominately case series, have evaluated a variety of medications in the prevention of taxane-induced arthralgias and myalgias. Results from these studies with glutamine,^2,3 Shakuyaku-Kanzou-to (an herbal medicine from Japan),^4-6 antihistamine,⁷ corticosteroids,^8,9 opioid analgesics,¹⁰ and amifostine^11-13 are inconclusive and/or conflicting. Therefore, there is no standard of care for the prevention of taxane-induced arthralgias and myalgias.¹⁴

Gabapentin is a second-line antiepileptic that has been used widely in the treatment of neuropathic and myofascial pain syndromes. For taxane-induced myalgias and arthralgias, a single case report showed that prophylactic gabapentin prevented symptoms in two patients, suggesting a role of gabapentin in this setting.¹⁵ Therefore, we retrospectively report our experience in using gabapentin in the prevention of taxane-induced arthralgias and myalgias.

In this retrospective study, eligible patients were identified by a verbal survey of oncologists and oncology-nurse practitioners at the San Francisco Veterans Affairs Medical Center (SFVAMC) who have used gabapentin to treat and/or to prevent taxane-induced arthralgias and myalgias, and by a search of computerized medical records of patients at the SFVAMC who received a taxane and gabapentin between April 1998 and February 2003. Medical records of all eligible patients were reviewed with approval by the Institutional Review Board of the University of California San Francisco.

Of the 10 patients identified, nine developed myalgias and arthralgias following the first cycle of a taxane. The remaining patient developed symptoms after the second cycle. These symptoms began 2 to 3 days following taxane infusion and lasted up to 7 days. Some patients reported diffuse symptoms, and others experienced pain localized to the large axial muscles and/or lower extremities. Four patients had disabling pain as described in the National Cancer Institute Common Toxicity Criteria, graded at 4, with the remaining patients complaining of moderate to severe pain that interfered with their activities of daily life. Three patients had concurrent neuropathy; patient 4 had severe symptoms of neuropathic pain of the lower extremities, and the remaining two patients had mild finger numbness. Myalgias and arthralgias developed despite prophylactic dexamethasone 20 mg, given 30 minutes before each taxane infusion, and additionally, dexamethasone 4 to 8 mg bid for 2 to 3 days for patients who received docetaxel. In one patient, prophylactic ibuprofen and low-dose dexamethasone (4 mg bid for 5 days) following docetaxel failed to prevent the development of myalgias and arthralgias on subsequent cycles. The remaining patients received no prophylactic therapy intended for myalgias and arthralgias other than gabapentin.

With the exception of one patient, gabapentin 300 mg tid was taken 2 days before and for 5 days after taxane infusion. In nine patients, gabapentin reduced or prevented myalgias and arthralgias with subsequent exposure to paclitaxel or docetaxel. Of these responders, three were asymptomatic, and six had only mild myalgias that did not interfere with daily activities. According to the National Cancer Institute toxicity scale, six patients had at least two grade reductions in symptoms. The remaining three responders had one grade reduction. A single patient developed severe myalgias and arthralgias despite prophylactic gabapentin. He had concurrent HIV infection, severe psychiatric disease, and neuropathy.

No major adverse events were reported with gabapentin. One patient reported mild dizziness, an adverse effect reported in up to 17% of patients on gabapentin.¹⁶ We did not observe other neurologic deficits or other previously reported adverse events, such as peripheral edema and gastrointestinal symptoms.

In sum, gabapentin given as secondary prophylaxis prevented or significantly reduced the severity of taxane-induced arthralgias and myalgias in a large majority (90%) of patients assessed in this case series. Gabapentin was effective in preventing both paclitaxel and docetaxel induced myalgias and arthralgias. The small number of patients in this series does not permit conclusions regarding patient characteristics that may predict response to gabapentin. Further studies to identify these characteristics as well as patients at risk for the development of taxane-induced myalgias and arthralgias may allow a risk-adapted strategy of prevention with gabapentin.

Recent clinical trials have expanded the use of taxanes to other cancers, including head and neck cancers, germ cell tumors, and hematologic malignancies. Hence, a larger number of patients are at risk for taxane-induced arthralgias and myalgias. Interventions with glutamine, corticosteroids, nonsteroidal antinflammatory drugs, antihistamines, and/or narcotics have yielded conflicting results and can be associated with adverse effects such as gastrointestinal bleeding, suppression of fevers and the immune response, and alteration of mental status. These problems may be more prominent with weekly or twice-weekly cycles of taxanes, which are currently under investigation.^17,18 Given its comparable cost to most drugs used for taxane-induced myalgias and arthralgias¹⁴ and the encouraging findings reported here, gabapentin is a viable treatment option in the prevention of taxane-induced arthralgias and myalgias.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

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