Timolol for TKI Induced Paronychia
Study Details
Study Description
Brief Summary
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.
Paronychia is one of the common adverse events in patients who receive EGFR-TKI(s). 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.
This study would assess the clinical efficacy of add-on topical timolol 0.5% gel to betamethasone valerate 0.1% for the treatment of EGFR-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% gel 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% gel twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% lotion twice daily with occlsuion 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The aim of this study ist o assess the clinical efficacy of add-on topical timolol 0.5% gel to betamethasone valerate 0.1% for the treatment of EGFR-TKI induced paronychia.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Timolol combination treatment Patients will received topical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month |
Drug: Topical Timolol
Topical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month.
|
| Active Comparator: Routine arm Patients in routine arm would receive the management according to routine clinical practice, including prescription of betamethasone valerate 0.1% cream twice daily for 1 month with occlusion. |
Drug: Topical Timolol
Topical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month.
|
Outcome Measures
Primary Outcome Measures
- The difference in the proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) [From baseline to month 3]
The primary outcome of this study is the proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) on topical timolol 0.5% eye drops as compared to betamethasone valerate 0.1% cream.
Secondary Outcome Measures
- The proportion of patients achieved complete or partial response [From baseline to month 3]
Proportion of patients achieved complete or partial response (improvement in at least 1 of these 3 items)
- Lack of response as well as proportion of patients with reduced severity of paronychia [From baseline to month 3]
- Change in chronic paronychia severity index scale with treatment [From baseline to month 3]
- The improvement of paronychia by 4 point scale [From baseline to month 3]
1: 0 to <30% , 2: 30 to <50% ,3: 50 to 75% ,4: 75 to 100 % improvement)
- Change in severity of pain by Visual Analog Scale [From baseline to month 3]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged 18 years or above, either males or females.
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Received EGFR-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib and mobocertinib.
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Paronychia (fingernails, toenails, or both) as an adverse event from EGFR-TKI use.
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Written informed consent obtained from patient.
Exclusion Criteria:
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Age below18.
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Patients who are allergic to, or contraindicated to topical timolol use.
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Pregnant women or nursing mother.
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Non-consenting patients.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Queen Mary Hospital | Hong Kong | Hong Kong |
Sponsors and Collaborators
- Queen Mary Hospital, Hong Kong
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UW 23-157