Can gemcitabine and/or paclitaxel cause drug-induced lung injury?

From the Guidelines

Yes, both gemcitabine and paclitaxel can cause drug-induced lung injury, with gemcitabine associated with pulmonary toxicity in approximately 1-2% of patients and paclitaxel causing lung injury in about 1-4% of patients. The lung injury typically presents as dyspnea, cough, fever, and hypoxemia, with radiographic findings showing diffuse interstitial or alveolar infiltrates 1. Risk factors include higher cumulative doses, combination chemotherapy regimens, prior lung disease, and concurrent radiation therapy. The onset can be acute (within days) or subacute (weeks to months) after drug administration. Management involves drug discontinuation, supportive care, and sometimes corticosteroids for severe cases. Some key points to consider when using these medications include:

• Monitoring respiratory symptoms in patients receiving these medications
• Performing baseline pulmonary function tests when possible
• Maintaining a high index of suspicion for drug-induced lung injury if respiratory symptoms develop during treatment
• Being aware of the potential for increased toxicity with combination chemotherapy regimens, as seen in the MPACT trial where gemcitabine plus albumin-bound paclitaxel was associated with improved overall survival but also increased adverse events such as neutropenia, fatigue, and neuropathy 1. It is essential to weigh the benefits and risks of using these medications, particularly in patients with pre-existing lung disease or other risk factors for drug-induced lung injury.

From the FDA Drug Label

Permanently discontinue Gemcitabine Injection for any of the following: Unexplained dyspnea or other evidence of severe pulmonary toxicity Clinically relevant Grade 3 or 4 dyspnea occurred with a higher incidence in the gemcitabine with paclitaxel arm compared with the paclitaxel arm (1.9% versus 0)

Gemcitabine can cause drug-induced lung injury, as evidenced by the warning to permanently discontinue the drug in cases of unexplained dyspnea or severe pulmonary toxicity. Additionally, the combination of gemcitabine and paclitaxel has been associated with a higher incidence of dyspnea.

• Key points:
  • Gemcitabine can cause severe pulmonary toxicity
  • The combination of gemcitabine and paclitaxel has a higher incidence of dyspnea compared to paclitaxel alone
  • Dyspnea is a symptom of drug-induced lung injury 2 2

From the Research

Drug-Induced Lung Injury

• Gemcitabine and paclitaxel have been associated with pneumonitis in non-small cell lung cancer patients, as reported in a phase I/II dose-escalating study 3.
• The study found that pneumonitis was the principal side-effect observed, with 4 patients affected, and all cases responded to prednisolone.
• Gemcitabine has also been linked to drug-induced lung injury, with risk factors including male gender, age 65 or over, smoking history, and first-line chemotherapy treatment 4.
• Nab-paclitaxel has been shown to cause drug-induced lung injury, with risk factors including age over 56 years, pre-existing interstitial lung changes, and combined use with gemcitabine 5.
• Severe acute lung injury has been reported in a patient receiving gemcitabine, highlighting the potential for pulmonary toxicity with this drug 6.
• Early detection and treatment of drug-induced pneumonitis with corticosteroids can lead to complete resolution of symptoms, as demonstrated in a case study of a patient with non-small cell lung cancer 7.

Risk Factors

• Age: older age (over 56 years) is a risk factor for drug-induced lung injury with nab-paclitaxel 5 and gemcitabine 4.
• Pre-existing interstitial lung changes: increases the risk of drug-induced lung injury with nab-paclitaxel 5.
• Combined use with gemcitabine: increases the risk of drug-induced lung injury with nab-paclitaxel 5.
• Smoking history: increases the risk of drug-induced lung injury with gemcitabine 4.
• Male gender: increases the risk of drug-induced lung injury with gemcitabine 4.