Docetaxel and irinotecan as first-line chemotherapy in patients with advanced non-small-cell lung cancer: a pilot study

The aim of this study is to evaluate the activity and toxicity of the combination docetaxel and irinotecan as first-line therapy for advanced non-small-cell lung cancer [NSCLC]. Twenty-two chemotherapy-naive patients with stage IIIB with pleural effusion or stage IV NSCLC received irinotecan 50 mg/m[2] on days 1, 8, and 15, and docetaxel 50 mg/m[2] on day 2, every 28 days until disease progression. Median follow-up was 10 months [range: 2-28 months]. The overall response rate was 36.4% [8/22 patients; 95% confidence interval: 16.8-56.0], with no complete responses. Median time to disease progression was 5 months [range: 1-24 months] and median overall survival was 10 months [range: 2-28]. Grade 3-4 diarrhea was observed in 2 patients [9.1%]. Grade 3-4 neutropenia occurred in 2 patients [9.1%]: 1 episode of febrile neutropenia in one patient, and 1 death due to neutropenic sepsis in another patient. One patient received transfusion for grade 4 anemia. Irinotecan showed a moderate response rate and overall survival of clinical interest. Diarrhea was the main toxicity. This regimen may be suitable for patients unable to tolerate cisplatin-based therapy, for elderly and/or for patients with poor performance status, and should be investigated in a larger trial

Sequential chemoradiotherapy versus concurrent chemoradiotherapy plus consolidation chemotherapy in unresectable stage III non-small cell lung cancer

To evaluate the efficacy and toxicity of concurrent/consolidation chemoradiotherapy versus sequential chemoradiotherapy in unresectable stage III non-small cell lung cancer [NSCLC]. Between January 2003 and April 2006 thirty-two patients with stage III unresectable NSCLC were randomly assigned to one of the two treatment arms. In the sequential arm, patients received induction chemotherapy with docetaxel [75 mg/m[2]] repeated every 3 weeks for 3 cycles, followed by thoracic radiotherapy at a dose of 61Gy in 33 fractions over 6.5 weeks. In the concurrent/ consolidation arm, the same radiotherapy was started on day 2 with two concurrent cycles of cisplatin 50 mg/m2 on days 1, 8, 29, and 36; etoposide 50 mg/m2 on days 1 through 5 and 29 through 33. Then these patients received consolidation therapy with docetaxel started 4-6 weeks after concurrent chemoradiotherapy, repeated every 3 weeks for 3 cycles at a dose of 75 mg/m[2]. The overall response rate was higher in concurrent/consolidation arm [62.5%] than in sequential arm [43.7%], [P=0.03]. The median survival was 19 months in concurrent/ consolidation arm and 13.6 months in the sequential arm, [P=0.001]. The 2- year survival rate was better in concurrent/ consolidation arm [43.7%] than in the sequential arm [25%], [P=0.03]. Median progression-free survival was longer in concurrent/consolidation arm [11.9 months] than in sequential arm [8 months], [P=0.07]. The major and most frequent toxicity was neutropenia, which was 43.7% in concurrent/consolidation arm versus 56.2% in sequential arm, [P=0.09]. However, esophageal toxicity [>/= grade 3] was relatively higher in concurrent/consolidation arm 18.7% versus 6.2% in sequential arm, [P= 0.05]. Brain metastasis was the most common site of distant failure in both treatment arms. Locoregional failure was more frequent in sequential arm [37.5%] than in concurrent/consolidation arm [18.7%], [P=0.04]. Consolidation docetaxel after concurrent cisplatin/ etoposide with radiotherapy in stage III NSCLC was feasible, tolerable and can be safely administered with relatively low incidence of radiation esophagitis. In addition, treatment outcomes compared favorably with the sequential chemoradiotherapy