ALK-TKI, EGFR-TKI, Paronychia
Conditions
Keywords
EGFR TKI, paronychia, timolol, ALK-TKI
Brief summary
To 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.
Detailed description
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.
Interventions
DRUGTimolol 0.5% eye drops and betamethasone valerate 0.1% cream
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. 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.
The management according to routine clinical practice, including prescription of betamethasone valerate 0.1% cream 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.
Sponsors
Queen Mary Hospital, Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
40 Adult patients aged 18 or above who received EGFR-TKI and ALK-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib, mobocertinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib for the treatment of non-small cell lung cancer, who develop paronychia (affecting fingernails, toenails or both),as an adverse event from EGFR-TKI use will be included in this study. Patients 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or above, either males or females. 2. Received EGFR-TKI and ALK-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib, mobocertinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib for the treatment of non-small cell lung cancer. 3. Paronychia (fingernails, toenails, or both) as an adverse event from EGFR-TKI use 4. Written informed consent obtained from patient 5. Subjects are diagnosed with advanced non-small cell lung cancer
Exclusion criteria
1. 1\. Age below18 2. 2\. Patients who are allergic to, or contraindicated to topical timolol use 3. 3\. Pregnant women or nursing mother 4. 4\. Non-consenting patients 5. 5\. Subjects are not diagnosed with advanced non-small cell lung cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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% lotion | From baseline to month 3 | 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% lotion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Proportion of patients lack of response (improvement in less than 1 item) |
| Change in chronic paronychia severity index scale with treatment | From baseline to month 3 | Involvement of 1 nail fold = 1; involvement of 2 nail folds \[proximal or/and lateral\] = 2; bilateral lateral nail fold involvement and proximal nail fold involvement = 3), edema (absent = 0; mild = 1; moderate = 2; severe = 3), erythema (absent = 0; mild = 1; moderate = 2; severe = 3), nail plate changes (absent = 0; mild = 1; moderate = 2; severe = 3), and cuticle involvement (normal = 0; damaged = 1; absent = 2), producing a combined total score (between 0 \[min.\] and 14 \[max.\] |
| 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 | VAS scores ≤3.4cm corresponded to mild pain-related interference with functioning, scores of 3.5-6.4 to moderate interference, and scores ≥6.5 to severe interference. |
Countries
Hong Kong
Contacts
Primary ContactWang Chun Kwok
Outcome results
None listed