Mitomycin-induced interstitial pneumonitis in a patient with BRCA2 associated metastatic pancreatic carcinoma.

Interstitial lung diseases are diffuse parenchymal lung diseases, and represent a heterogeneous group of disorders including lymphocytic interstitial pneumonitis, interstitial lung diseases of unknown etiology, including sarcoidosis, idiopathic pulmonary fibrosis, and pulmonary fibrosis associated with connective tissue diseases [1]. Most of the interstitial disorders have a restrictive pattern with reductions in total lung capacity, functional residual capacity, and residual volume [2]. The lung has significant susceptibility to injury from a variety of chemotherapeutic agents (Table 1). The clinician must be familiar with classic chemotherapeutic agents with well-described pulmonary toxicities and must also be vigilant about a host of new agents that may exert adverse effects on lung function [3]. BRCA2 mutations have been known to be associated with higher incidence of breast, ovarian and pancreatic adenocarcinoma [4, 5, 6]. Although present in only a minority of pancreatic cancers, mutations in the BRCA2 gene could provide a rational target for treatment with chemotherapeutic agents. Van der Heijden et al. have demonstrated that pancreatic cancer cells having defects in Fanconi anemia and BRCA2 pathway are remarkably sensitive to mitomycin-C both in culture and mice [7, 8]. Isacoff et al. reported good results with mitomycin-C plus fluorouracil regimen in first-line therapy of locally advanced pancreatic cancer, with two out of 50 patients achieving complete remission [9]. Another study using the same regimen in patients with metastatic pancreatic carcinoma also showed some activity including one complete remission [10]. We present here a case of a mitomycin-induced interstitial lung disease in a patient with BRCA2 associated metastatic pancreatic carcinoma. Our patient presented at the age of 71 years with a dual diagnosis of locally advanced prostate carcinoma and metastatic pancreatic carcinoma on the background of a significant family history of cancer. On genetic testing, he was found to have the common Ashkenazi Jewish BRCA2 mutation, 6174delT. He initially received 22 cycles of docetaxel, capecitabine, and gemcitabine followed by single agent irinotecan every 3 weeks for 27 cycles, and then weekly cetuximab was added to the regimen at cycle 28. His disease then remained stable for an additional 13 months. He did not have mutated K-ras. Upon progression on irinotecan/cetuximab, he was switched to mitomycin-C and oxaliplatin. He immediately developed hypersensitivity reaction to oxaliplatin, and single agent mitomycin-C was continued at 7 mg/m every 21 days. After three cycles of mitomycin-C, he presented to the oncology clinic with dry cough, progressive dyspnea, and hypoxemia. Pulse oximetry showed 96% at room air. A CT angiogram of chest showed right middle lobe ground glass changes without pulmonary embolism. Subsequent CT scan showed persistent nodules and ground glass opacity. Patient underwent bronchoscopy, and right middle lobe appeared to be generally unremarkable. Transbronchial biopsy of right middle