Introduction
Materials and methods
Study design
Eligibility criteria
Evaluation and statistical analysis
Results
Patient characteristics
Gender | |
Male/female (n) | 3/12 |
Age (years), median (range) 79 (75–87) | |
ECOG PS [n (%)] | |
0–1 | 13 (86.7) |
2 | 2 (13.3) |
Clinical stage [n (%)] | |
IIIB | 2 (13.3) |
IV | 11 (73.4) |
Recurrence | 2 (13.3) |
Histological type [n (%)] | |
Adenocarcinoma | 15 (100) |
Smoking history [n (%)] | |
Never smoker | 12 (80) |
Light smoker | 3 (20) |
EGFR mutation [n (%)] | |
Exon 19 del | 3 (20) |
Exon 21 L858R | 11 (73.4) |
Exon 18 G719 | 1 (6.6) |
No. of prior treatment regimen [n (%)] | |
0 | 13 (86.7) |
1–2 | 2 (13.3) |
MTD and toxicity analysis
Treatment level | Afatinib (mg/day) | ||
---|---|---|---|
Level 1 20 mg/day n = 6 | Level 2 30 mg/day n = 3 | Level 3 40 mg/day n = 6 | |
Patients number | 6 | 3 | 6 |
DLT, n (%) | 1 (16.7) | 0 | 2 (33.3) |
Details of DLTs | 77 years, female Grade 3 rash, anorexia and infection | 75 years, female Grade 3 diarrhea 80 years, female Grade 3 diarrhea, and anorexia |
Afatinib | 20 mg | 30 mg | 40 mg | All dose | ||||
---|---|---|---|---|---|---|---|---|
n = 6 | n = 3 | n = 6 | n = 15 | |||||
Grade (CTCAE) ver4.0 | 1–2 | 3 | 1–2 | 3 | 1–2 | 3 | All grade (%) | 3 (%) |
Neutropenia | 1 | 0 | 0 | 0 | 0 | 0 | 1 (6.6) | 0 |
Anemia | 3 | 0 | 3 | 0 | 1 | 0 | 7 (46.6) | 0 |
Thrombocytopenia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Nausea, vomiting | 3 | 0 | 1 | 0 | 2 | 1 | 7 (46.6) | 1 (6.6) |
Anorexia | 1 | 1 | 2 | 0 | 2 | 1 | 7 (46.6) | 2 (13.3) |
Fatigue | 2 | 0 | 2 | 0 | 2 | 0 | 6 (40) | 0 |
Diarrhea | 6 | 0 | 3 | 0 | 4 | 2 | 15 (100) | 2 (13.3) |
Skin rush | 2 | 1 | 3 | 0 | 4 | 2 | 12 (80) | 3 (20) |
Paronychia | 0 | 0 | 3 | 0 | 3 | 0 | 6 (40) | 0 |
Oral mucositis | 0 | 0 | 2 | 0 | 3 | 0 | 5 (33.3) | 0 |
Increased AST | 2 | 0 | 0 | 0 | 1 | 0 | 3 (20) | 0 |
Infection | 1 | 1 | 0 | 0 | 1 | 0 | 3 (20) | 0 |
Increased Creatinine | 0 | 0 | 0 | 0 | 1 | 0 | 1 (6.6) | 0 |
Efficacy
Response | Number of patients | % |
---|---|---|
Complete response | 0 | 0 |
Partial response | 11 | 73.3 |
Stable disease | 3 | 20.1 |
Progressive disease | 0 | 0 |
Not evaluable | 1 | 6.6 |
Response rate | 73.3% |