Fludarabine

BETHESDA, MD. -- The chemotherapy agent fludarabine can induce pulmonary toxicity that resembles the symptoms of pulmonary infection, Dr. Donald L. Helman reported at the annual meeting of the Washington, D.C., Chapter of the American College of Physicians--American Society of Internal Medicine.

Differentiating pulmonary toxicity from infection is essential because patients are unlikely to recover without aggressive steroid therapy to counter the drug's toxic effects.

"Consider the possibility of pulmonary toxicity in any patient treated with fludarabine who develops fever, cough, dyspnea, hypoxia, and new interstitial infiltrates," said Dr. Helman of the Walter Reed Army Medical Center, Washington, D.C.

Fludarabine is widely used as chemotherapy for hematologic malignancies, particularly low-grade lymphoproliferative disorders such as chronic lymphocytic leukemia, the most common form of leukemia among adults.

The agent is known to increase the incidence of opportunistic infections, notably pneumocystis pneumonia. Although a few case reports of pulmonary toxicity have been published, "until now very little was known as to whether or not this particular chemotherapeutic agent directly causes pulmonary toxicity," Dr. Helman said.

He conducted a retrospective case series to obtain a better clinical description of fludarabine-induced pulmonary toxicity. The series included eight patients who had the disorder, which is characterized by fever, cough, dyspnea, hypoxia, and pulmonary infiltrates on radiograph in the absence of infection or cancer progression.

The subjects included seven men and one woman; the median age was 65 years. Six patients were receiving fludarabine to treat chronic lymphocytic leukemia, one patient was receiving it to treat pro-lymphocytic leukemia, and one patient was receiving it to treat lymphoma.

Pulmonary symptoms generally occurred during the first or second cycle of chemotherapy, but they could appear as late as the seventh cycle.

All the patients were presumed to have pulmonary infection and were initially treated with broad-spectrum antibiotics pending culture results. One patient died within 1 day

Five of the remaining seven patients underwent bronchoscopy, which revealed neutrophilic alveolitis in all five. All subjects were negative for Pneumocystis infection as well as for infection with Legionella, herpes simplex virus, cytomegalovirus, bacteria, and my-cobacteria.

None of the patients showed malignant involvement of the lungs, he said.

The seven surviving patients received aggressive steroid therapy; all had a prompt response, within a median of 4 days. All patients recovered from the drug's toxic effects and had no chronic pulmonary problems.

"These findings show that although fludarabine is generally safe and well tolerated, it can cause pulmonary toxicity. The mechanism of toxicity is unknown, but fortunately the problem responds to aggressive steroid therapy," Dr. Helman said.

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