O-1 A phase III trial comparing weekly and three weekly docetaxel in second line treatment of patients with advanced non small cell lung cancer (NSCLC)

Purpose Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC. Patients and Methods A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m2 intravenously (IV) on days 1 to 3 or topotecan 1.5 mg/m2 IV on days 1 to 5. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival (PFS), and safety. Results Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan (HR, 0.802; P = .018). ORR was 31.1% with amrubicin and 16.9% with topotecan (odds ratio, 2.223; P < .001). Grade ≥ 3 treatment-emergent adverse events in the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004), thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001), respectively. NQO1 polymorphisms did not influence safety outcomes. Conclusion Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC. OS did not differ significantly between treatment groups, although an improvement in OS was noted in patients with refractory disease treated with amrubicin.

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Phase III Study of Second-Line Chemotherapy for Advanced Non–Small-Cell Lung Cancer With Weekly Compared With 3-Weekly Docetaxel

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.3739 ◽

2005 ◽

Vol 23 (33) ◽

pp. 8389-8395 ◽

Cited By ~ 139

Author(s):

Wolfgang Schuette ◽

Sylke Nagel ◽

Thomas Blankenburg ◽

Christine Lautenschlaeger ◽

Klaus Hans ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Phase Iii ◽

Second Line ◽

Small Cell Lung ◽

Weekly Docetaxel ◽

Phase Iii Study ◽

Grade 3

Purpose A phase III study to determine whether a weekly docetaxel schedule improves the therapeutic index compared with the classic 3-weekly schedule. Patients and Methods Patients with stage IIIB-IV non–small-cell lung cancer (NSCLC) were randomly assigned to docetaxel 75 mg/m2 on day 1 every 3 weeks (3-weekly) and 35 mg/m2 on days 1, 8, and 15 (weekly) for ≤ eight cycles. End points included survival (primary), toxicity, and response. Results Of 215 patients enrolled, 208 (103 in the 3-weekly arm and 105 in the weekly arm) were assessable for response. At baseline, 24.5% of patients (51 out of 208) had received prior paclitaxel therapy and 43.3% of patients (90 out of 208) had been progression-free for more than 3 months after first-line therapy. After 12 months' follow-up, median survival was 6.3 months (95% CI, 4.68 to 7.84 months) with 3-weekly docetaxel and 9.2 months (95% CI, 5.83 to 12.59 months) with weekly docetaxel (P = .07) after a median of four (range, one to eight) and two (range, one to eight) treatment cycles, respectively. Overall, response rates were 12.6% v 10.5% with 3-weekly versus weekly docetaxel. Significantly fewer patients reported grade 3 to 4 toxicities with weekly docetaxel versus 3-weekly docetaxel (P ≤ .05). There were significantly lower rates of grade 3 to 4 anemia (P ≤ .05), leucopenia (P < .0001), and neutropenia (P ≤ .001) with weekly versus 3-weekly treatment. No grade 3 to 4 thrombocytopenia or mucositis was reported. Conclusion Weekly docetaxel 35 mg/m2 demonstrated similar efficacy and better tolerability than standard 3-weekly docetaxel 75 mg/m2 and can be recommended as a feasible alternative second-line treatment option for patients with advanced NSCLC.

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