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Vol.58 No.4 contents | Japanese/English |
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- Original Article -
Clinical, Endoscopic and Histologic Features of Lung Cancer Patients with Programmed Cell Death Protein 1 (PD-1) Inhibitor-associated Diarrhea and Colitis
Noriko Mitome1, Haruhiro Saito1, Yuji Shibata1, Isuke Shimokawaji1, Tetsuro Kondo1, Terufumi Kato1, Tomoyuki Yokose2, Kouzo Yamada11Department of Thoracic Oncology, 2Department of Pathology, Kanagawa Cancer Center, Japan
Background. Programmed cell death protein 1 (PD-1) inhibitors are used in the treatment of non-small cell lung cancer; however, these drugs can cause immune-related adverse events that have never been witnessed in patients undergoing chemotherapy and even death. Diarrhea is one of the common side effects, and hence it is important to properly manage it. Method. In total, 131 patients who were administered PD-1 inhibitors for metastatic non-small cell lung cancer between January 2016 and August 2017 were identified. We retrospectively studied the clinical course and findings of 14 patients who developed diarrhea after treatment. Result. Twelve patients received nivolumab, and 2 patients received pembrolizumab. The median age was 67 years old (range 49-77), the male/female ratio was 11/3, and the median time between the first infusion and the diarrhea onset was 9.3 weeks (range 1-47). The number of cases for each grade of diarrhea was as follows: grade 1 (n = 11), grade 2 (n = 2), grade 3 (n = 1), and grade 4 (n = 0); however, in 4 cases of grade 1, the diarrhea worsened to grade 2 during treatment. Six patients underwent a colonoscopy and pathological examination, respectively. Drug administration was stopped in 78.6% of patients (n = 11), while 71.4% of patients (n = 10) received systemic glucocorticosteroids, and the diarrhea improved in all patients; therefore, no patient required infliximab. In 1 case involving glucocorticosteroid administration, the patient developed cytomegalovirus infection and received ganciclovir. In 14 cases, the response rate was 50%, and the tumor control rate was 78.6%. The administration of PD-1 inhibitors resumed in 4 cases after improvement of the diarrhea, but the symptoms recurred in all cases, and the patients had to stop using the drug. Conclusions. In our retrospective analysis, PD-1 inhibitor-associated diarrhea had various clinical and endoscopic features. The diarrhea improved in all cases with the discontinuation of the use of PD-1 inhibitors or with the use of glucocorticosteroids. In all cases where drug administration resumed, diarrhea recurred; we should therefore resume drug administration only after careful consideration.
key words: Programmed cell death protein 1 (PD-1) inhibitor, Diarrhea, Colitis
Received: March 1, 2018
Accepted: April 22, 2018
JJLC 58 (4): 262-270, 2018
