Introduction
Patients with advanced cancer frequently develop multiple severe symptoms with a negative impact on their quality of life. Off-label drug use is a frequent practice in palliative care (PC) for the management of multiple symptoms (Hagemann et al. Reference Hagemann, Bausewein and Remi2019; Kwon et al. Reference Kwon, Kim and Bruera2017).
Olanzapine is an atypical neuroleptic indicated for treatment of various psychiatric disorders, but in the setting of PC, its off-label use is increasing not only for nausea/vomiting related to chemotherapy but also (Fonte et al. Reference Fonte, Fatigoni and Roila2015; Saudemont et al. Reference Saudemont, Prod’Homme and Da Silva2020) for opioid misuse (Go et al. Reference Go, Song and Lee2018; Juliào et al. Reference Juliào, Sobral and Ferreira2022b) and symptoms such as anorexia-cachexia, anxiety, and sleep disorders (Bonar et al. Reference Bonar, Schneider and Cook2023; Davis and Sanger Reference Davis and Sanger2021; Dev et al. Reference Dev, Fortuno and Amaram-Davil2023).
Peripheral edema occurs in approximately 3% of patients receiving olanzapine, and there are a few case reports of facial edema (Cook et al. Reference Cook, Shipman and Fowler2020; Kuppili et al. Reference Kuppili, Nebhinani and Jain2018; Malhotra and Shrivastava Reference Malhotra and Shrivastava2013; NG et al. Reference NG, Postlewhite and Rollnik2003). The pathophysiology of this adverse event may be related to vasodilatation and disturbance of fluid regulation and electrolyte balance. There is only 1 case report of facial edema in a cancer patient in PC (Juliào et al. Reference Juliào, Lemos-Caldas and Ulrich2022a).
We report a case of a 74-year-old man with advanced cancer who developed moderate tongue edema on day 1 of therapy with 2.5 mg olanzapine daily.
Case presentation
A 74-year-old man with advanced colon cancer with multiple liver metastases who refused further chemotherapy due to severe toxicity and disease progression was referred to our outpatient service on March 2023. His past medical history was negative for allergies, other significant or other medical problems.
When his oncologist reported disease progression, the patient was comfortable with his decision to discontinue cancer treatment.
He felt that he was happy about his life as a successful musician, a painter, and a gourmet, and he stated “I have no pain and no distressful symptoms for now; I can still play my music, eat my favorite foods, take long walks and also long phone calls with my sons! I cannot heal, but I can still wholly live my life. And you’ll help me not to suffer when that time will come.”
In December 2023, he developed a cluster of symptoms including insomnia, anxiety related to prognosis, nausea and worsening of cachexia-anorexia syndrome, and he received a prescription of 2.5 mg of olanzapine daily.
Seven days after the beginning of therapy, the patient called and reported that on day 1 he experienced an episode of tongue swelling, burning mouth, and sore throat. He discontinued olanzapine on day 2, with rapid resolution. The edema and the other symptom disappeared within 24 hours; he did not present lower extremity edema, bronchospasm or airway compromise, itch, or other dermatological signs.
Physical examination showed no other possible differential diagnoses, and the patient stated that he did not start any new drugs or foods prior to the tongue edema.
Laboratory tests excluded any other organic factors, and the Naranjo Algorithm described a probable drug reaction to olanzapine (Naranjo et al. Reference Naranjo, Busto and Sellers1981).
Although the event did not worsen the quality of life of the patient or his symptoms, it caused anguish on his awareness of prognosis related to symptoms’ burden and possible future drug reactions. We had a candid conversation about his personal outcomes and the quality of life, and he reported joy at having his 2 sons and their families at home for Christmas.
He was also happy to give full consent to this case report.
Discussion
To the best of our knowledge, this is the second case reporting edema in the head and neck region due to olanzapine treatment in a patient with advanced cancer receiving PC (Juliào et al. Reference Juliào, Sobral and Ferreira2022b) and the first reporting a tongue edema as adverse drug reaction.
Our patient had good performance status (ECOG-1: restricted in strenuous activity), but he was elderly and with advanced cancer as the patient in the Juliao et al. report. The clinical course suggests that this rare adverse event might not be related to drug dose but rather to clinical factors as advanced cancer and elder age. More research is needed in order to better understand the pathophysiology of olanzapine-related edema.
Considering the increasing use of olanzapine as off-label treatment in PC (often for cluster symptoms), our report could increase awareness of this rare and potentially serious complication that can be rapidly resolved after olanzapine discontinuation.
Acknowledgments
Thanks to Silvia Tanzi and Luca Ghirotto from USL-IRCCS Reggio Emilia, Italy, for your constant endorsement not to give up with research!
Funding
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Competing interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.