Safety of sequential immune checkpoint inhibitors after prior immune therapy.

BACKGROUND: The use of immune checkpoint inhibitors (ICI) has transformed cancer treatment. Subsequent ICI use has become increasingly common following disease progression. We aim to evaluate the safety and tolerability of the sequential ICI treatment modality. METHODS: Retrospective review of confirmed carcinoma from January 2014 to December 2018. Patients were categorized into "initial ICI arm" and "sequential ICI arm" defined as patients receiving single, dual or chemo-immunotherapy ICI following an initial ICI regimen. Primary outcome was the development of a new or recurrent immune related adverse event (irAE) during sequential therapy. Secondary outcomes were the number of cycles prior to the development of irAE and grade of irAE. RESULTS: A total of 483 patients received ICI during the timeframe. Of those, 22 patients received sequential ICI. The diagnoses included ten lung cancer, seven melanoma, four renal cell carcinoma and one bladder cancer. 16 patients received single agent ICI following the initial ICI, three patients received dual ICI following the initial ICI, one patient received chemotherapy-immunotherapy following initial ICI, and two patients received chemo-immunotherapy after dual ICI. Four patients developed new irAE and one patient developed the same irAE on sequential treatment. A higher proportion of patients experienced grade 3 irAE in the sequential arm compared to the initial ICI arm (p = 0.03). No statistical difference was found between the development of irAE and the number of cycles prior to development of irAE in either treatment groups (p = 0.5). CONCLUSION: Our data shows overall safety of sequencing ICI when close monitoring was employed.

Integrative Therapies During and After Breast Cancer Treatment: ASCO Endorsement of the SIO Clinical Practice Guideline.

Purpose The Society for Integrative Oncology (SIO) produced an evidence-based guideline on use of integrative therapies during and after breast cancer treatment that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. ASCO considered the guideline for endorsement. Methods The SIO guideline addressed the use of integrative therapies for the management of symptoms and adverse effects, such as anxiety and stress, mood disorders, fatigue, quality of life, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Interventions of interest included mind and body practices, natural products, and lifestyle modifications. SIO systematic reviews focused on randomized controlled trials that were published from 1990 through 2015. The SIO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. Results The ASCO Expert Panel determined that the recommendations in the SIO guideline-published in 2017-are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline with a few added discussion points. Recommendations Key recommendations include the following: Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-l-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy because of a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related adverse effects. Additional information is available at: www.asco.org/supportive-care-guidelines .

Early-Onset 5-Fluorouracil Toxicity in a Patient Negative for Dihydropyrimidine Dehydrogenase Mutations: The Clinical Course of Reversal with Uridine Triacetate.

An antimetabolite pyridine analog, 5-fluorouracil (5-FU), is used to treat solid tumors. Early toxicities may occur at standard doses of 5-FU due to dihydropyrimidine dehydrogenase (DPD) deficiency. Uridine triacetate, approved by the Food and Drug Administration in 2015, is an oral prodrug of uridine, a pharmacologic antidote for 5-FU toxicity. To our knowledge, this is the first case report that documents the clinical course of a patient treated with uridine triacetate to reverse early-onset 5-FU toxicity negative for DPD mutations. We describe the case of a 73-year-old man with anal cancer treated with standard-of-care chemotherapy and radiation. Two days after completion of his initial 5-FU infusion, the patient developed severe mucositis and extreme fatigue, followed by a rapid decline in his blood cell counts and fevers. The patient was initiated on uridine triacetate 86 hours after completion of his 5-FU infusion. Over a 10-day hospital length of stay, the patient's absolute neutrophil count recovered to within normal limits, and his mucositis significantly improved. At follow-up visits, the patient denied any residual symptoms of 5-FU toxicity. We describe the patient's clinical course from hospital presentation to 31 days after initiation of uridine triacetate.