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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0b013e3181d6b9e8
Letters to the Editor

Pemetrexed-Induced Fluid Retention

Bastos, Diogo Assed MD; Calabrich, Aknar MD; Katz, Artur MD

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Oncology Center, Sírio Libanês Hospital, São Paulo, Brazil

From the Oncology Center, Sirio Libane's Hospital, São Paulo, Brazil.

Disclosure: The authors declare no conflicts of interest.

Address for correspondence: Artur Katz, MD, Oncology Center, Sírio Libanês Hospital, São Paulo, Brazil. E-mail:

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To the Editor:

Despite the favorable toxicity and safety profiles of pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, IN), several adverse events have been reported, including blood and lymphatic system disorders, gastrointestinal disorders, and general disorders.1–3 In this letter, we describe a case series consisting of seven patients who developed clinically significant fluid retention, an uncommon adverse effect associated with the use of pemetrexed. All patients have received vitamin supplementation and were pretreated with corticosteroids as indicated in the package insert (Table 1).

Table 1
Table 1
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Other causes of edema were excluded, and all patients had normal echocardiogram, normal levels of B-type natriuretic peptide and albumin, normal renal, hepatic, and thyroid function tests, and no significant proteinuria. Most patients presented with mild-to-moderate edema, mainly in periorbital area, as illustrated in Figure 1 (case 1). Of the seven cases, only one patient (case 4) developed grade 3 refractory edema with symptomatic bilateral effusion. A bilateral thoracocentesis was necessary for symptom relief, and the pleural effusion analysis was consistent with an exudate with no malignant cells and negative cultures. There was complete disappearance of generalized edema and bilateral pleural effusion after discontinuation of pemetrexed treatment. Another patient (case 6) also had complete resolution of the edema after pemetrexed was discontinued because of disease progression. All other cases were managed with observation only or salt restriction and diuretics, with limited control of this side effect. Because of sustained partial responses and disease control, treatment with pemetrexed was continued in all but one patient, which was described above, despite the incomplete control of this problem.

Figure 1
Figure 1
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Pemetrexed-associated peripheral and eyelid edema has been rarely reported, with an estimated incidence of 1% in clinical trails.1,4 To our knowledge, there were no severe cases reported with need for treatment discontinuation until now. The mechanism involved in the development of fluid retention and consequent edema is unknown, but may be because of capillary leakage syndrome.4 Now that pemetrexed has demonstrated efficacy in the first-line setting and is an option as maintenance or early second-line therapy, more patients will be exposed to this agent, and therefore more individuals will potentially develop this treatment-related adverse effect. Therefore, we believe it is important to report this unusual adverse event and to understand its pathophysiology to attempt to develop strategies to avoid and manage this uncommon side effect.

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The authors thank the patients for their explicit consent for sharing their clinical information in this report, especially Mrs. ANPC for allowing us to use her photograph for illustration.

Diogo Assed Bastos, MD

Aknar Calabrich, MD

Artur Katz, MD

Oncology Center

Sírio Libanês Hospital

São Paulo, Brazil

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1.Hanna N, Shepherd FA, Fossella FW, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non–small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004;22:1589–1597.

2.Russo F, Bearz A, Pampaloni G. Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer. BMC Cancer 2008;8:216.

3.Pujol JL, Paul S, Chouaki N, et al. Survival without common toxicity criteria grade 3/4 toxicity for pemetrexed compared with docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): a risk-benefit analysis. J Thorac Oncol 2007;2:397–401.

4.Kurata T, Tamura K, Okamoto I, et al. Pemetrexed-induced edema of the eyelid. Lung Cancer 2006;54:241–242.

© 2010International Association for the Study of Lung Cancer


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