Antineoplastic agents can cause oral toxicity, including “antineoplastic agents-associated stomatitis” (AAS) and “antineoplastic agents-associated oral Candidiasis” (AAOC), in children, adults, and older cancer patients.
Objective
To identify the risk of AAS and AAOC associated with using antineoplastic agents.
Methods
The FDA FAERS database for spontaneously reported adverse effects of “antineoplastic agents” was searched and analysed for the occurrence of the MedDRA preferred term “stomatitis” and “oral Candidiasis” using “quantitative safety signal analysis”, which contains spontaneous safety reports collected from 1976 to the end of 2021.
Results
The results of stomatitis in 27477 and oral candidiasis in 3136 case reports from the FDA database, which received antineoplastic agents during the treatment process. Among all three age groups studied, 4 and 7 antineoplastic agents were strongly associated with the occurrence of AAOC and AAS, respectively (reported odds ratio [ROR] > 100), and the lowest association with AAOC and AAS was reported in 19 and 33 antineoplastic agents, respectively (ROR < 1).
Conclusion
There are several limitations to providing information on the side effects of new antineoplastic agents in drug databases. Signal detection in pharmacovigilance is a process in which safety issues, including possible drug-related side effects, are investigated. Our study highlights the gap in the database regarding the potential risk of AAOC and AAS, as reported by the FDA for new drugs.
WongHM. Oral complications and management strategies for patients undergoing cancer therapy. Scientific World J2014; 2014: 1–14.
2.
VenkateshCJaniMShahA. Oral complications of chemotherapy: a review. J Adv Med Dent Sci Res2015; 3: S99.
3.
PulitoCCristaudoAPortaCL, et al.Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res2020; 39: 1–15.
4.
NaiduMURamanaGVRaniPU, et al.Chemotherapy-induced and/or radiation therapy-induced oral mucositis-complicating the treatment of cancer. Neoplasia2004; 6: 423–431.
5.
da Cruz CamposMICamposCNAarestrupFM, et al.Oral mucositis in cancer treatment: natural history, prevention and treatment. Mol Clin Oncol2014; 2: 337–340.
6.
ChaudhrySEhteshamZ. Treatment options for cancer patients suffering from oral mucositis. Asian Pac J Cancer Care2023; 8: 181–184.
7.
SufiawatiIPratiwiUWijayaI, et al.The relationship between Candida albicans colonization and oral hygiene in cancer patients undergoing chemotherapy. Mater Today Proc2019; 16: 2122–2127.
8.
LallaRVLatortueMCHongCH, et al.A systematic review of oral fungal infections in patients receiving cancer therapy. Support Care Cancer2010; 18: 985–992.
9.
DuggiralaHJTonningJMSmithE, et al.Use of data mining at the Food and Drug Administration. J Am Med Inform Assoc2016; 23: 428–434.
10.
DuMouchelW. Bayesian Data mining in large frequency tables with an application to the FDA spontaneous reporting system. Am Stat1999; 53: 177–190.
11.
SzarfmanAMachadoSGO’NeillRT. Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the US FDA’s spontaneous report database. Drug Saf2002; 25: 381–392.
12.
EladSYaromNZadikY, et al.The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies. CA Cancer J Clin2022; 72: 57–77.
13.
LiJGongCZhouH, et al.Kinase inhibitors and kinase-targeted cancer therapies: recent advances and future perspectives. Int J Mol Sci2024; 25: 5489.
14.
DudaDGJainRK. Revisiting antiangiogenic multikinase inhibitors in the era of immune checkpoint blockade: the case of sorafenib. Cancer Res2022; 82: 3665–3667.
15.
VigariosEEpsteinJBSibaudV. Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors. Support Care Cancer2017; 25: 1713–1739.
16.
MakitaSMaeshimaAMMaruyamaD, et al.Forodesine in the treatment of relapsed/refractory peripheral T-cell lymphoma: an evidence-based review. Onco Targets Ther2018; 11: 2287–2293.
17.
MalikSMLiuKQiangX, et al.Folotyn (pralatrexate injection) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma: uS food and drug administration drug approval summary. Clin Cancer Res2010; 16: 4921–4927.
18.
FouladiMPerentesisJPWagnerLM, et al.A phase I study of cixutumumab (IMC-A12) in combination with temsirolimus (CCI-779) in children with recurrent solid tumors: a children's oncology group phase I consortium report. Clin Cancer Res2015; 21: 1558–1565.
19.
KöstlerWJHejnaMWenzelC, et al.Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J Clin2001; 51: 290–315.
20.
MiwaSYamamotoNHayashiK, et al.Recent advances and challenges in the treatment of rhabdomyosarcoma. Cancers (Basel)2020; 12: 1758.
21.
ConneelySECooperSLRauRE. Use of allopurinol to mitigate 6-mercaptopurine associated gastrointestinal toxicity in acute lymphoblastic leukemia. Front Oncol2020; 10: 1129.
22.
van DalenECvan AsJWde CamargoB. Methotrexate for high-grade osteosarcoma in children and young adults. Cochrane Database Syst Rev2011; 2011: Cd006325.
23.
AdenisABlayJ-YBui-NguyenB, et al.Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann Oncol2014; 25: 1762–1769.
24.
NowaraEHusznoJ. Masitinib plus gemcitabine for personalized treatment of PDAC patients with overexpression of ACOX1. Expert Rev Precis Med Drug Dev2016; 1: 479–485.
25.
von MinckwitzGProcterMde AzambujaE, et al.Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med2017; 377: 122–131.
26.
MannBSJohnsonJRCohenMH, et al.FDA Approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist2007; 12: 1247–1252.
27.
González-BurgosEGómez-SerranillosMP. Chapter 4 - Vinca alkaloids as chemotherapeutic agents against breast cancer. In: BrahmachariG (eds) Discovery and development of anti-breast cancer agents from natural products. Amsterdam, The Netherlands: Elsevier, 2021, pp.69–101.
28.
GerullisHWawroschekFKöhneC-H, et al.Vinflunine in the treatment of advanced urothelial cancer: clinical evidence and experience. Ther Adv Urol2017; 9: 28–35.
29.
LiuLXuZYuB, et al.Berbamine inhibits cell proliferation and migration and induces cell death of lung cancer cells via regulating c-maf, PI3K/akt, and MDM2-P53 pathways. Evidence-Based Complementary Altern Med2021; 2021: 5517143.
30.
MengZLiTMaX, et al.Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca2+/calmodulin-dependent protein kinase II. Mol Cancer Ther2013; 12: 2067–2077.
31.
GerullisHWawroschekFKöhneC-H, et al.Vinflunine in the treatment of advanced urothelial cancer: clinical evidence and experience. Ther Adv Urol2017; 9: 28–35.
32.
SchutzFABBellmuntJRosenbergJE, et al.Vinflunine: drug safety evaluation of this novel synthetic vinca alkaloid. Expert Opin Drug Saf2011; 10: 645–653.
33.
PloumakiITriantafyllouEKoumprentziotisI-A, et al.Bcl-2 pathway inhibition in solid tumors: a review of clinical trials. Clin Transl Oncol2023; 25: 1554–1578.
34.
Di MaioMScagliottiGV. The lesson learned from figitumumab clinical program and the hope for better results in squamous lung cancer. Transl Lung Cancer Res2015; 4: 15–17.
35.
YoshiokaHOkudaTNakaoT, et al.Experience with tirabrutinib in the treatment of primary central nervous system lymphoma that is difficult to treat with standard treatment. Anticancer Res2022; 42: 4173–4178.
36.
BeelenDWTrenschelRStelljesM, et al.Treosulfan or busulfan plus fludarabine as a conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomized, non-inferiority, phase 3 trial. Lancet Haematol2020; 7: e28–e39.
