Pemetrexed-induced severe rhabdomyolysis in lung cancer: A case report

Abstract

Pemetrexed is an antifolate metabolite used to treat non-small cell lung cancer in the adjuvant and advanced setting. It is commonly known to cause rash, diarrhea, fatigue, mucositis, and myelosuppression. We report a case of a patient receiving adjuvant cisplatin and pemetrexed for non-small cell lung adenocarcinoma and experienced severe rhabdomyolysis.

Keywords : Non-small cell lung cancer, pemetrexed, rhabdomyolysis

Introduction

Pemetrexed, an antifolate metabolite, is used to treat non-small cell lung cancer (NSCLC) in the adjuvant and advanced setting.1,2 Some common adverse events include rash, diarrhea, fatigue, mucositis, and myelosuppression, which can often be ameliorated by cyanocobalamin and folate supplementation. Rhabdomyolysis has been previously reported with pemetrexed in one patient with malignant pleural meso- thelioma and one patient with lung adenocarcinoma.3,4 Many clinicians may be unaware of this rare adverse reaction. Here, we describe a case of rhabdomyolysis associated with pemetrexed.

Case presentation

A 58-year-old man was diagnosed with stage IIB lung cancer, classified as T3N0M0 non-small cell lung adenocarcinoma. Patient underwent a right upper lob- ectomy and mediastinal lymph node dissection with resection of the second rib. Postoperatively, the patient was started on adjuvant chemotherapy with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every three weeks. The patient received cyanocobalamin and folate supplementation, as well as a premedication regi- men of dexamethasone, palonosetron, and aprepitant.

The patient’s other routine medications included ome- prazole and metoprolol tartrate. At the start of chemo- therapy, the patient also received two doses of ferumoxytol for iron-deficiency anemia. The patient experienced fatigue with the first two cycles of chemo- therapy. About 10 days after cycle 3, the patient was hospitalized for severe weakness and low back pain and was found to have an elevated creatine kinase (CK).
The patient presented to the emergency department unable to ambulate and walk for the prior 24 h com- plaining of severe lower back pain. He denied any trauma. Blood work revealed a CK level of 12,480 U/L and AST/ALT were mildly elevated. Laboratory values throughout the hospitalization are trended in Table 1. The patient was treated with aggressive intra- venous fluid hydration with clinical improvement.

During his hospital course, CK downtrended signifi- cantly. Orthopedic surgery was consulted but no surgical intervention was necessary. By the time of discharge, lower back pain improved and he was ambulating normally.

Due to his initial presentation with back pain, computed tomography (CT) thoracic/lumbar spine was performed which was negative for metastatic disease. CT of the chest was performed with no

Sullivan and Lee 3

acute findings. The probability of pemetrexed causing rhabdomyolysis is calculated in Table 2.

Discussion

We describe a patient who experienced non-traumatic rhabdomyolysis after receiving pemetrexed chemother- apy for adjuvant NSCLC. It is well known that certain prescribed medications can result in rhabdomyolysis as well as drug–drug interactions potentiating rhabdo- myolysis. None of the patient’s other medications are known to cause rhabdomyolysis, and there were no known potential medication interactions that could result in adverse events. This appears to be an uncom- mon and a rare adverse event of pemetrexed chemo- therapy. In patients receiving this chemotherapy drug in the adjuvant or metastatic setting, who seek medical attention for pain-related symptoms, often the under- lying malignancy will be high among the differential diagnosis. Rhabdomyolysis can lead to arrhythmias, renal failure, and be fatal if not identified and treated appropriately.

In conclusion, clinicians should be aware of the rare, potentially life-threatening adverse event of rhabdo- myolysis in patients receiving pemetrexed chemotherapy.