For patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the relationship between the dose or duration of treatment with tyrosine kinase inhibitor (TKI) and overall survival remains unclear. Here, we analyzed clinical data of 39 patients who were diagnosed with EGFR mutation-positive non-small cell lung cancer and treated with TKI, but subsequently died. Several parameters were measured in this study: overall survival; first, second, and overall TKI therapy durations; first TKI intensity (actual dose/normal dose); and TKI rate (overall TKI therapy duration/overall survival). The response rate to TKI therapy was 50%, and the median survival was 553 days. After TKI therapy failed, 38.5% patients were re-challenged with TKI. We observed a moderate relationship [r = 0.534, 95% confidential interval (CI) = 0.263 to 0.727, P < 0.001] between overall TKI therapy duration and overall survival. However, we found no relationship between overall survival and first TKI intensity (r = 0.073, 95% CI = -0.380 to 0.247, P = 0.657) or TKI rate (r = 0.0345, 95% CI = -0.284 to 0.346, P = 0.835). Non-small cell lung cancer patients with mutation-positive tumors remained on TKI therapy for, on average, 33% of the overall survival time. These findings suggest that patients with EGFR mutation-positive tumors should not stick to using TKIs.
Aged ; Aged, 80 and over ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Dose-Response Relationship, Drug ; Erlotinib Hydrochloride ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; administration & dosage ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Quinazolines ; administration & dosage ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Survival Rate

BACKGROUNDTo summarize the effect of Iressa for refractory patients with advanced non small cell lung cancer (NSCLC) failed to prior chemotherapy.

METHODSThirty-one patients, with unresectable stage IIIB or IV NSCLC who had disease progression or relapse after prior chemotherapy using platinum-based regimen for at least 2 cycles, were admitted to the Osaka Prefectural Hobikino Hospital. Iressa 250 mg was administered once a day until disease progression was noted. Weekly chest x-ray and monthly CT scan were performed for response assessment each month.

RESULTSAmong the 31 patients, one complete response (CR) and 7 partial responses (PR) were observed. CR rate was 3.2% (95% confidence interval: 0-17%), PR rate 22.6% (95% confidence interval: 10%-41%), disease control rate including both tumor responses and stable disease was 80.6% (95% confidence interval: 52%-92%). The rate of symptoms relieves was 51.6% (95% confidence interval: 33%-70%), the most effective symptoms being cough and pain. The median time to improved symptoms was 14 days. The most common adverse events were grade I or II skin rash and diarrhea which were readily manageable and reversible. No patients were withdrawn due to the adverse events

CONCLUSIONSMonotherapy using Iressa is effective and tolerable for the patients with advanced NSCLC who failed prior chemotherapy.