Update on the role of nanoliposomal irinotecan in the treatment of metastatic pancreatic cancer.

Median survival for patients with metastatic pancreatic cancer (MPC) treated with combination chemotherapeutic agents such as gemcitabine-based regimens and FOLFIRINOX is currently less than 12 months. This highlights the need for more efficacious first-line, as well as second-line therapies. Nanoliposomal irinotecan, in combination with 5-fluorouracil (5-FU)/folinic acid has recently been assessed as second-line therapy after initial gemcitabine-based therapy. It is the first, second-line treatment approved by the US Food and Drug Administration to treat patients with MPC based on results of the NAnoliPOsomaL Irinotecan (NAPOLI-1) study, which showed that this regimen significantly prolonged progression-free survival (3.1 months versus 1.5 months) and overall survival (6.2 months versus 4.1 months) compared with 5-FU/folinic acid alone. In addition, this study also represented an important step forward in improving the efficacy of previously used chemotherapeutic agents by using nanoformulation to extend pharmacokinetic advantages such as slow clearance, low steady-state volume of distribution, and longer half-life. However, certain adverse effects that are seen more frequently with nanoliposomal irinotecan and 5-FU/folinic acid, compared with 5-FU/folinic acid alone, include neutropenia, fatigue, diarrhea, and nausea/vomiting. This merits close monitoring of patients who are on this combination, since these adverse events may necessitate dose reductions and growth factor support. It is imperative to check UGT1A1 gene status in all patients being considered for treatment with nanoliposomal irinotecan. Patients found to be homozygous for the UGT1A1*28 gene need to be started on a lower initial dose. As we gain more data with clinical use, we anticipate further characterization of the aforementioned toxicities in patients with UGT1A1 gene polymorphisms and other genetic variants.

Pseudomembranous aspergillar tracheobronchitis in a non-neutropenic critically ill patient in the intensive care unit.

Invasive aspergillosis is an important cause of morbidity and mortality among immunocompromised patients. Prolonged neutropenia is the most common risk factor. It has rarely been reported to occur in non-neutropenic critically ill patients in the intensive care unit setting. Mortality rate in this group has been reported to be as high as 92%. We report a case of tracheobronchial aspergillosis in a non-neutropenic critically ill patient to highlight the fact that critically ill patients admitted in the intensive care unit can develop opportunistic infections such as invasive aspergillosis even in the absence of classic risk factors and prior history of immunosuppression. Early diagnosis and prompt initiation of antifungal therapy may improve the outcome and decrease mortality rate.