Severe Gemcitabine-Associated Lung Injury in Hodgkins Disease & Other Cancers: Reporting Quality and Clinical Characteristics of Cases Reported in the Medical Literature and to the FDA.

Background: In view of concern about substantially increased risk of gemcitabine-associated lung injury (ALI), vigilant post-marketing surveillance is necessary to further characterize the frequency, severity, and clinical features of gemcitabine-associated pulmonary injury.

Methods: From 2001–2003, investigators with the Research on Adverse Drug reactions And Reports (RADAR) program compared the clinical characteristics and adverse event reporting quality of gemcitabine-associated lung injury contained in published case reports and adverse event reports submitted in the setting of clinical trials or the non-clinical trial setting.

Results: Completeness of reporting was excellent for published case reports and intermediate to poor for FDA adverse event reports from clinical trials or observational studies, including age (100%, 92%, 91%); time to onset of toxicity (100%, 63%, 58%); dose (97%, 63%, 79%); results of imaging studies (94%, 56%, 59%); presence/absence of hypoxia (97%, 6%, 4%); and cause of death (88%, 82%, 66%). Temporal analyses identified a bimodal pattern for the onset of pulmonary symptoms: 90% occurred before 150 days and 8% after 300 days. The highest rates of severe lung injury were in high dose patients co-administered bleomycin (28%) and in lung cancer patients (16%).

Conclusions: Reporting completeness for severe gemcitabine-ALI to the FDA from the clinical trial and the non-clinical trial setting is poor, limiting the ability of the RADAR group to comprehensively assess this toxicity. Nonetheless, this toxicity is severe and, as shown in published case reports, frequent in the presence of concomitant pulmonary insults such as bleomycin-containing combination chemotherapy regimens for Hodgkin’s disease and taxol-containig combination chemotherapy regimens for lung cancer.

Gemcitabine-associated Acute Lung Injury in Selected Clinical Trials