Correct!
1. Stop gemcitabine
Of the agents the patient was receiving, gemcitabine is the drug most commonly associated with pulmonary toxicity. Treatment of drug induced lung disease involves stopping the offending agent. Although no randomized trial has been performed, corticosteroids are often added and anecdotally may hasten resolution of the lung toxicity. This was done in this case and the patient had marked clinical improvement a month later. We speculate the delay in symptoms between her last gemcitabine therapy and her symptoms might have been due to the corticosteroids she was receiving for her brain metastasis.
Acute dyspnea with infusion of gemcitabine occurs in about 10% of subjects. There appear to be three types of gemcitabine lung toxicity:
The frequency of lung toxicity is relatively low at about 0.27% of patients receiving the drug. Reduction in DLco within 2 months of treatment has been reported in 24% of patients, but this is often self-limited. The reduction in DLco appears to be more frequent in women, older age, and those with a low baseline DLco. Some cases of pulmonary fibrosis are reported, but are rare. Factors increasing the risk of lung injury include other chemotherapy (including paclitaxel) and chest radiation. The mortality rate with acute pneumonitis is up to 20%, but rapid response to steroid therapy has been reported.
Iniparib is a poly(adenosine diphoshate-ribose) polymerase (PARP) inhibitor. A recent phase 2 trial in metastatic “triple negative” breast cancer reported 123 patients given iniparib with or without gemcitabine/carboplatin. Iniparib improved survival from 7.7 months to 12.3 months. Dyspnea was reported, but no severe pulmonary complications from iniparib were reported in this study.
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