Abstract
Introduction: Targeted therapies for the treatment of metastatic NSCLC are associated with a distinct set of adverse side effects that differ clinically from those seen with chemotherapies. Our institution has been actively involved in clinical trials of ALK inhibitors, and have gained extensive experience in managing patients receiving these agents. Symptom management (medication or non-medication based) is patient-centric and involves a multi-specialty team who share the goal of maintaining patients on appropriate palliative therapy. Here we present 3 cases illustrating symptom management strategies for ALK inhibitors, focusing on fatigue, anorexia, gastrointestinal toxicities, and transaminitis.
Discussion: Case 1: A 79-year-old woman with ALK+ NSCLC was treated initially with pemetrexed followed by crizotinib. Crizotinib-associated nausea and diarrhea were managed with ondansetron, but activity-limiting fatigue was problematic. For fatigue we screened for insomnia, sleep apnea, depression, and polypharmacy. This patient benefited from low-dose trazodone with improvement of sleep and fatigue. She was treated with an antidepressant for depression/anxiety and referred to physical therapy for general strengthening, which enabled her to travel with family. At disease progression the patient initiated ceritinib and experienced an associated reduction in tumor burden in the chest and brain, resulting in improvement in chest pain, cough and dyspnea. Reduced appetite was problematic and thoroughly evaluated. The patient benefitted from referral to nutrition and increased ondansetron. Case 2: A 45-year-old woman with metastatic ALK+ NSCLC underwent spinal and whole-brain radiation. She initiated ceritinib 750 mg and dose reduced to 600 mg upon reporting significant diarrhea and prolonged QTc; nausea and emesis remained severe despite dose reduction. Good effect was found with oral ondansetron and atropine/diphenoxylate dosed 30 minutes before and prochlorperazine 30 minutes after taking ceritinib. This patient benefited from dosing at night, evaluation of psychosocial factors, management of reflux, close monitoring, and encouragement in taking medications. Case 3: A 60-year-old man presented with metastatic NSCLC, renal, and cardiac comorbidities. At confirmation of ALK+ disease he was started on crizotinib, followed by ceritinib upon progression. One month after starting ceritinib, tumor responses were seen in the chest and brain, but he developed grade 3 transaminitis. Repeated episodes of transaminitis have been managed with dose reduction, holding of drug until normalization of liver function, and biweekly monitoring of liver function with good ongoing tumor control. Conclusion: A comprehensive approach to managing symptoms associated with targeted therapies for metastatic NSCLC can enable patients to remain on palliative treatments for several years that are both tolerable and effective in controlling cancer growth.
