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Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Efficacy of this drug was documented in the BR.21 trial showing that adenocarcinoma, female gender, Asian ethnicity and never-smoker status are predictive of clinical response to erlotinib. Retrospective studies documented the same benefits for elderly patients as young patients in terms of response, progression-free survival, and overall survival. The primary aim of our trial was to confirm these findings in a prospective way; the secondary aim was to identify if the aforementioned clinical characteristics may be predictive of response even in elderly patients. The trial included 31 patients with pretreated stage IIIB (2) and IV (29) non-small cell lung cancer (NSCLC). Median age was 75 years (range: 65-85). Twenty-seven patients were current/former-smokers and four never-smokers. Twenty-three patients are evaluable for response. Objective response rates were reported in five patients (16%). Five patients had stable disease (16%) and 13 progressive disease (43%). Seven patients had a "clinical benefit" from erlotinib (22.5%; 95% C.I.: 7.9-37.2%). Grade 3 skin rash was recorded in three patients (10%). Median survival was 9 months (range 1-30). Median time to progression was 3 months (range: 1-24 months). Our study confirmed erlotinib activity and safety as second- and third-line treatment in elderly patients with advanced NSCLC, especially in terms of median survival. Even though this trial does not allow us to draw a definitive conclusion about the role of a particular clinical characteristic predictive of response, the "clinical benefit" was documented especially in females, in patients with adenocarcinoma histology and skin rash, confirming previous retrospective data.

PURPOSE: Intravenous vinorelbine has demonstrated its efficacy and tolerability in advanced non–small-cell lung cancer (NSCLC). An oral formulation of vinorelbine has been developed, and a number of phase II studies have shown its activity in chemotherapy-naive NSCLC, even in elderly patients, but no study has been performed to test activity and toxicity of oral vinorelbine in pretreated patients. The aims of our study were to investigate the activity and toxicity of oral vinorelbine in patients with NSCLC as salvage treatment. PATIENTS AND METHODS: Twenty pretreated patients with locally advanced (n = 6) and metastatic (n = 14) NSCLC entered the study. The schedule was oral vinorelbine 60 mg/m2 once a week until progression or development of unacceptable toxicity. Median age was 70 years (range, 49-84 years). RESULTS: Seventeen patients were evaluable for response and all for toxicity. A median of 9 cycles were administered (range, 2-21 cycles). No objective responses were reported, 5 patients experienced stable disease, and 12 patients had progressive disease. Median time to progression was 2 months (range, 1-6 months), and median survival was 4 months (range, 1-13 months). Treatment was well tolerated, with grade 4 neutropenia in 1 patient (heavily pretreated); grade 2 diarrhea in 2 patients; asthenia in 2 patients; and abdominal pain in 1 patient. CONCLUSION: Oral vinorelbine 60 mg/m2 once a week is a very safe schedule in heavily pretreated locally advanced and metastatic NSCLC; however, at this dose, the drug is inactive. Other phase II studies with oral vinorelbine 80 mg/m2 weekly are warranted.

Introduction Single-agent docetaxel is active as second-line chemotherapy in non-small cell lung cancer (NSCLC) pretreated patients; seven phase II studies have shown response rates of about 20% and 9 months of median survival. Two phase III studies documented a survival benefit at 1 year compared to BSC and vinorelbine or ifosfamide. Recent trials indicate acceptable activity and a good safety profile of weekly docetaxel with doses of 25–43 mg/m2. The aim of our study was to confirm this evidence and to evaluate activity and toxicity of weekly docetaxel at the dose of 40 mg/m2. Patients and methods Twenty-one patients with NSCLC entered the study (7 stage NIB and 14 stage IV): 13 males and 8 females. Median age was 66 years (range, 53–75). ECOG was O in 6, 1 in 9 and 2 in 6 patients. All patients were pretreated with a first-line chemotherapy (13 patients progressed soon after the first line); 6 of them received palliative radiotherapy on the chest. The treatment consisted of weekly docetaxel, 40 mg/m2 in 1 hr for six weeks with two weeks of rest (1 cycle). A total of 87 administrations was delivered (median, 4; range, 1–12). Responses All patients were assessable for response (according to the “intent-to-treat principle”) and for toxicity. No complete or partial remission was observed; 2 minor responses (9.5%), 1 stable disease (5%), 8 progressive diseases (38%) were documented. Seven patients dropped out the study due to severe toxicity (33.5%) and 3 due to early death (14%). Median survival was 3 months (range, 1–17), and 1-year survival was 9.5%. Toxicity was as follows: grade 4 diarrhea in 1; grade 3 asthenia in 8 (38%), grade 3 stomatitis in 2; grade 3 neutropenia in 1; allergic reactions in 2. No treatment-related death was recorded. Conclusions The trial showed only very modest activity of weekly docetaxel, with severe side effects that induced us to stop the accrual in order to prevent other worse toxicities. We therefore concluded that a dose of 40 mg/m2 of weekly docetaxel is not manageable and does not seem to provide a real benefit in terms of response and quality of life.

Purpose: Paclitaxel and platinum-based chemotherapy is considered to be a standard approach for locally advanced and metastatic non–small-cell lung cancer (NSCLC). In recent years, weekly paclitaxel has been widely used for its safety profile, especially in breast and ovarian cancer. Otherwise, only a few studies are available in NSCLC. The aim of our study was to investigate the activity and safety of weekly paclitaxel in elderly patients with locally advanced (stage IIIB) and metastatic (stage IV) NSCLC. Patients and Methods: Twenty-seven patients entered the study; 10 had stage IIIB disease (5 “wet” and 5 “dry”), and 17 had stage IV disease. Median age was 73 years (range, 70-83 years). Sixteen patients (59%) presented with comorbidities. The schedule was weekly paclitaxel 80 mg/m2 for 6 weeks with 2 weeks of rest (1 cycle). Results: All patients were evaluable for response and toxicity; a median of 1 cycle was administered (range, 1-5 cycles). Partial responses were recorded in 9 patients (37.5%; 33.3%, according to intentionto-treat analysis; 95% CI, 15.5%-51.1%); 7 had stable disease (29%), and 8 had progressive disease (33.5%). Median time to progression was 5 months (range, 1-23 months), and median survival was 12 months (range, 1-36 months). Grade 2/3 asthenia was the main toxicity in 7 patients (29%); a hypersensitivity reaction presented in 1 patient. No other episode of grade 3/4 toxicity was recorded. Conclusion: Our study confirmed that paclitaxel 80 mg/m2 weekly is active in patients with locally advanced and metastatic NSCLC with a good safety profile; this schedule might be considered an alternative choice to gemcitabine or vinorelbine as first-line treatment in elderly patients, particularly patients with comorbidities. Phase III studies that compare these third-generation drugs are warranted to draw definitive conclusion about the best approach in these patients.