Predictive and prognostic significance of neuron-specific enolase (NSE) in non-small cell lung cancer.

BACKGROUND: The predictive and prognostic role of neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC) is still under debate. PATIENTS AND METHODS: To study these aspects, serum NSE was prospectively measured at baseline of first-line chemotherapy treatment and tested for correlation with clinical outcome in 129 advanced NSCLC patients. RESULTS: An objective response was achieved in 27 out of 65 (41.5%) patients with NSE < 8.6 ng/ml and in 38 out of 64 (59.4%) patients with NSE > or = 8.6 ng/ml (p = 0.05). Logistic analysis confirmed the positive association between objective response and NSE values > or = 8.6 ng/ml (odds ratio = 1.69; 95% confidence interval: 1.09-2.63; p = 0.02). Overall median survival was 10.8 months. A statistically significant prognostic effect on survival was found for performance status, stage and response to treatment, but not for baseline NSE value. CONCLUSION: Based on these data, baseline circulating tumor NSE levels appear to have a weak predictive role, but not a prognostic significance in patients with advanced NSCLC submitted to standard chemotherapy.

Phase II study of Taxol combined With ifosfamide and carboplatin in the treatment of stage IIIb-IV non-small-cell lung cancer.

The objective of the present study was to evaluate the activity and the toxicity of an original combination of paclitaxel (Taxol), ifosfamide, and carboplatin in patients with stage IIIB-IV non-small-cell lung cancer (NSCLC). Sixty-one patients with previously untreated stage IIIB-IV NSCLC were enrolled by five institutions. Paclitaxel was given at the dose of 200 mg/m iv in 3 hours, ifosfamide (with mesna) at the dose of 3 g/m and carboplatin at an area under the curve 5, on day 1, every 21 days for a total of six cycles in responding or stabilized patients. Among the 59 patients evaluable for response, 2 complete remissions and 25 partial remissions were achieved for an overall response rate of 45.7% (95% CI = 32.7-59.2). According to an intention-to-treat analysis, the response rate was 44.2%. Thirteen patients had a stable disease, whereas 19 progressed. The median time to progression was 7.7 months (range: 1-18), whereas the median overall survival was 10 months (range: 1-30+). The 1-year survival rate was 43%. Hematologic toxicity was exceptionally mild, and peripheral neurologic toxicity of grade III was experienced by only three patients. There was one toxic death. This original triplet regimen based on paclitaxel, ifosfamide, and carboplatin has proved active, safe, and easy to deliver on an outpatient basis for patients with advanced NSCLC. Randomized studies both versus carboplatin-paclitaxel and other triplets are clearly warranted.

Induction chemotherapy with carboplatin-paclitaxel followed by standard radiotherapy with concurrent daily low-dose cisplatin plus weekly paclitaxel for inoperable non-small-cell lung cancer.

Both induction chemotherapy and concurrent platinating agents have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study investigated activity and feasibility of a novel chemoradiation regimen, including platinum and paclitaxel, both as induction chemotherapy and concurrently with thoracic radiotherapy. Previously untreated patients with histologically/cytologically proven unresectable stage I-III NSCLC were eligible. Induction chemotherapy consisted of 2 courses of 200 mg/m2 paclitaxel and carboplatin at AUC of 6 mg/mL/min every 3 weeks. From day 43, continuous thoracic irradiation (60 Gy in 30 fractions radiotherapy for 6 weeks) was given concurrently with daily cisplatin at a dose of 5 mg/m2 intravenously and weekly paclitaxel at a dose of 45 mg/m2 for 6 weeks. Fifteen patients were accrued in the first stage of the trial. According to the previous statistical considerations, accrual at the second stage of the study was halted as a result of the achievement an insufficient number of successes. Major toxicity of combined chemoradiation was grade III-IV esophagitis requiring hospitalization for artificial nutrition, which occurred in 58% of patients. Other toxicities included grade II-IV fatigue in 75% of patients and grade I-IV neuromuscular toxicity in 67%. Only 7 patients completed the treatment program as scheduled. Eight patients (53.3%; 95% confidence interval, 26.5-78.7%) had a major response (5 partial response, 3 complete response), 2 patients had disease progression, and 1 was stable at the end of treatment. Four patients died early. With a median follow up of 38 months, the median survival was 12 months. A combined chemoradiation program, including platinum and paclitaxel, appears difficult to deliver at full dose as a result of toxicity, mainly esophagitis. More active and less toxic combined modality treatments need to be developed for inoperable NSCLC.