Chest
Volume 129, Issue 4, April 2006, Pages 1031-1038
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Original Research
A Randomized Trial of Different Docetaxel Schedules in Non-small Cell Lung Cancer Patients Who Failed Previous Platinum-Based Chemotherapy

https://doi.org/10.1378/chest.129.4.1031Get rights and content

Study objective

Docetaxel has shown activity in the second-line treatment of non-small cell lung cancer (NSCLC). Phase II studies have suggested that weekly therapy with docetaxel probably has a better toxicity profile than the conventional schedule of once every 3 weeks. Our aim was to evaluate and compare the efficacy of different docetaxel schedules in NSCLC patients who did not respond to previous platinum-based chemotherapy.

Setting

National teaching hospital in Taiwan.

Methods

Treatment consisted of the following: (1) docetaxel, 35 mg/m2 IV infusion (D35) on days 1, 8, and 15 every 4 weeks; (2) docetaxel, 40 mg/m2 IV (D40) on days 1 and 8 every 3 weeks; and (3) docetaxel, 75 mg/m2 IV (D75) on day 1 every 3 weeks. Patients were randomized at a ratio of 2:2:1, with the D75 arm as the control arm. From 2002 to 2004, 161 patients were enrolled into the study.

Results

The number of patients enrolled in each arm of the study was as follows: D35 group, 64 patients; D40 group, 64 patients; D75 group, 33 patients. The mean ages of patients were as follows: D35 group, 65 years of age; D40 group, 63 years of age; D75 group, 64 years of age. The median number of cycles of chemotherapy received in each group was as follows: D35 group, 4; D40 group, 3; D75 group, 4. The objective response rates were as follows: D35 group, 17.2%; D40 group, 10.9%; D75 group, 6.1% (p = 0.615). The major toxicity was myelosuppression. Grades 3/4 leukopenia and neutropenia were significantly higher in the D75 arm of the study (p < 0.001). Drug-induced pneumonitis occurred more frequently in patients on a weekly schedule than in those on a schedule of every 3-weeks (p = 0.05). The median survival times were as follows: D35 group, 8.4 months; D40 group, 7.2 months; and D75 group, 9.5 months (p = 0.855). The 1-year survival rates were 32.8%, 31.9%, and 28.7%, respectively. Lung cancer symptom scores showed no obvious differences among the different treatment arms, except for some minor items.

Conclusions

Weekly docetaxel chemotherapy produces less myelosuppression, and better compliance and response rates than the conventional chemotherapy administered every 3 weeks. These effects were more evident in the D35 group weekly schedule than in the D40 weekly schedule. However, physicians should pay more attention to the possibility of a higher frequency of docetaxel-induced pneumonitis in patients receiving treatment on the weekly schedule of treatment.

Section snippets

Materials and Methods

The study was conducted according to the existing rules for good clinical practice, and the study protocol was approved by the local ethics committee. Patients with NSCLC who had not responded to previous platinum-based chemotherapy, aged ≥ 18 years, were entered into the study after giving informed consent. The eligibility criteria were as follows: a histologic or cytologic diagnosis of stage IIIb or IV NSCLC in patients who had not responded to previous platinum-based chemotherapy; a

Results

Patients’ clinical characteristics are shown in Table 1. There was no statistical difference in the patients’ clinical characteristics among the different treatment arms. The mean age of patients was about 64 years, and more than half of the patients had a performance status of 2. All patients had been previously treated with platinum-based combination chemotherapy. In this study, docetaxel was the second-line chemotherapy in 146 patients and was third-line or greater chemotherapy in 15

Discussion

In phase II trials of NSCLC patients,15 single-agent docetaxel, 75 or 100 mg/m2, produced objective response rates of 14 to 25% in second-line treatment. Two phase III randomized trials45 revealed that single-agent docetaxel provided meaningful survival and clinical benefits in second-line NSCLC treatment, thus, establishing docetaxel as the standard second-line treatment for NSCLC. The dose recommended in this setting is 75 mg/m2 every 3 weeks.456 However, a dosage of 60 mg/m2 every 3 weeks

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