Lung cancer is the second leading cause of cancer and the leading cause of cancer-related
death in Hong Kong. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer
patients. Adenocarcinoma and squamous cell carcinoma accounts for 40% and 25-30% of NSCLC
patients, respectively. More than 75% of patients are diagnosed with stage III and IV
lung cancer. The age-standardized one-year overall survival rate of stage III and IV
NSCLC are 35-46% and 15.9-15.6%, respectively. Therefore, the management of locally
advanced and metastatic lung cancer is important to improve the overall survival of NSCLC
patients.
The management of locally advanced and metastatic NSCLC is actionable driver mutation
dependent. Patients are recommended to have tissue biopsy to detect the actionable driver
mutation. Epidermal growth factor receptor (EGFR) mutation accounts for 55.4% of
actionable driver mutation in Hong Kong. Patients with EGFR mutation positive are
recommended to receive EGFR tyrosine kinase inhibitor (EGFR-TKI) by the European Society
of Medical Oncology and the National Comprehensive Cancer Network. Anaplastic lymphoma
kinase (ALK) is another common is actionable driver mutation with tyrosine kinase
inhibitor (TKI) including crizotinib, ceritinib, alectinib, brigatinib and lorlatinib.
Paronychia is one of the common adverse events in patients who receive EGFR-TKI(s) and
other TKI. 17.6-57% of patients experienced paronychia in randomized controlled trials.
There were 0.6-11% of patients who experienced grade 3 paronychia according to the Common
Terminology Criteria for Adverse Events version 5.0 (CTCAEv5.0) in randomized controlled
trials.
Timolol and betaxolol are beta-blockers, which are hypothesized to be effective in
managing paronychia. Beta-blockers were effective in hemangiomas and has been the first
line treatment for severe infantile hemangiomas. Previous case reports and case series
suggested the potential use of topical beta-blocker. However, the evidence of topical
beta-blocker treatment was limited by small sample size and low level of evidence.
Therefore, this study aims to compare the safety and efficacy of topical timolol with
routine clinical care with paronychia (fingernails, toenails, or both) as an adverse
effect of EGFR-TKI and ALK-TKI.
This study would assess the clinical efficacy of add-on topical timolol 0.5% eye drops to
betamethasone valerate 0.1% for the treatment of EGFR-TKI and ALK-TKI induced paronychia.
Eligible patients, who develop paronychia (affecting fingernails, toenails or both), will
be included in this study. They will be randomized in 1:1 ratio using computer-generated
randomization list to receive either combination of topical timolol 0.5% eye drops and
betamethasone valerate 0.1% lotion application twice daily or betamethasone valerate 0.1%
lotion application twice daily. Patients in timolol combination treatment group will
receive topical timolol 0.5% eye drops twice daily with occlusion (i.e. covered with
adhesive badge) and betamethasone valerate 0.1% lotion twice daily with occlusion for 1
month. Patients in routine arm would receive the management according to routine clinical
practice, including prescription of betamethasone valerate 0.1% lotion twice daily for 1
month with occlusion. For patients who do not have paronychia completely resolved after 4
weeks, the treatment assigned will be continued for another 4 to 8 weeks , up to 12 weeks
to see the effect.
