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Docetaxel for Previously Treated Non-Small-Cell Lung Cancer

Docetaxel for Previously Treated Non-Small-Cell Lung Cancer

ABSTRACT: Two phase III trials were conducted using docetaxel (Taxotere), administered every 3 weeks, as second-line treatment of non-small-cell lung cancer (NSCLC) in patients previously treated with platinum-based chemotherapy. In the TAX 317 trial, 204 patients were randomized to receive either docetaxel (49 received 100 mg/m² and 55 received 75 mg/m²) or best supportive care (100 patients). Median survival was 7.5 months with docetaxel at 75 mg/m² (D75) vs 4.6 months for best supportive care (P = .010); and 1-year survival was 37% for D75 vs 11% for best supportive care (P = .010). Quality-of-life analysis also showed statistically significant improvement in disease-related symptoms with docetaxel vs best supportive care. In the TAX 320 study, 373 patients were randomized to receive docetaxel at 100 mg/m² (D100), docetaxel at 75 mg/m² (D75), or a control arm of either vinorelbine (Navelbine) or ifosfamide (Ifex) (V/I). Partial response rates were 11.9% with D100 and 7.5% with D75 vs 1% with V/I (P values: .001 [D100] and .036 [D75]). Median response duration was over 7 months. One-year survival was 32% with D75 vs 19% in V/I (P = .025). Prior paclitaxel exposure had no bearing on the response rate and survival advantage of second-line treatment with docetaxel. Response rates to docetaxel were equivalent in the cohort of patients who had received prior paclitaxel (10.5%) and the group of patients who had not received prior paclitaxel (8.5%). The 1-year survival rates for patients with no prior paclitaxel therapy were 33% (D75) vs 20% (V/I); and the 1-year survival rates for patients who had received prior paclitaxel were 30% (D75) vs 17% (V/I). In conclusion, two large randomized phase III trials of second-line chemotherapy for NSCLC have shown significant differences favoring docetaxel for response rate, time to progression, survival, and quality of life. Prior paclitaxel did not decrease the likelihood of response to docetaxel, nor did it lessen the survival advantage seen with docetaxel. Docetaxel offers a clinically meaningful benefit in this setting, with manageable toxicity. Based upon the observed response rates, survival, impact on quality of life, and toxicity profile, the optimal dose of docetaxel in this pretreated population is 75 mg/m² every 3 weeks. [ONCOLOGY 16(Suppl 6):45-51, 2002]

In the past several years, medical
oncologists have become increasingly aware that a subset of patients with
advanced non-small-cell lung cancer (NSCLC) may benefit from second-line
chemotherapy after the failure of first-line therapy. Most of the data in
support of the use of second-line chemotherapy has been with docetaxel (Taxotere).

Docetaxel as a first-line agent for advanced NSCLC showed
consistent response rates in phase II trials that ranged from 23% to 38%.[1-5]
Average median survival is 39 weeks and 1-year survival is 34%. Docetaxel also
has been systematically evaluated in the second-line setting for NSCLC patients
whose disease has progressed or failed to respond to first-line platinum-based
chemotherapy. Objective radiographic responses were consistently seen in four
phase II studies of docetaxel in the second-line setting, and ranged from 16% to
22%.[4-8] Favorable survival rates were noted as well in these trials; the
median survival rate ranged from 5.8 to 9.8 months, and the estimated 1-year
survival rate ranged from 25% to 44% (Table 1).[4,6-8]

The most compelling evidence to support docetaxel’s
activity in the second-line treatment of NSCLC comes from two large randomized
phase III trials that compared docetaxel with either best supportive care (TAX
317) [9] or a comparator regimen of chemotherapy (TAX 320) [10] (Figure

Phase III Trial of Docetaxel vs Best Supportive Care

The TAX 317 trial was a multicenter international trial of
second-line chemotherapy with docetaxel reported by Shepherd.[9,11] Eligible
patients had advanced NSCLC that had progressed during or after one or more
platinum-containing chemotherapy regimens. There was no restriction on the
number of prior chemotherapy cycles or regimens, and there was no restriction on
the prior chemotherapy agents permitted (with the exception that patients with
prior paclitaxel exposure were excluded). Patients were required to have an
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Patients
with treated brain metastases were included in the trial.

Eligible patients were stratified by their best response to
prior platinum-based chemotherapy and performance status and then randomly
assigned to receive either docetaxel every 3 weeks or best supportive care.
The initial trial design called for a docetaxel dose of 100 mg/m² (D100) as a
1-hour IV infusion every 3 weeks. However, because of an unexpectedly high
occurrence of adverse events occurring at this dose level, the protocol was
subsequently modified to a docetaxel dose of 75 mg/m² (D75) every 3 weeks.

A total of 204 patients were enrolled in this trial: 49
received docetaxel at 100 mg/m², 55 received docetaxel at 75 mg/m², and 100
received best supportive care. Patient characteristics and updated results are
summarized in Table 2. About 80% of patients had stage IV disease, and nearly
25% of patients had a performance status of 2. The demographics with regard to
age and gender were typical for this patient population and were well balanced
among the treatment groups. The predominant histology was adenocarcinoma.
One-quarter of patients had received two or more prior chemotherapy regimens
before enrollment.

Partial response was observed in 6% of patients treated with
docetaxel (either dose level), and another 40% of patients had stable disease.
The median response duration was 26 weeks. Time to progression favored
treatment with docetaxel vs best supportive care. The median time to progression
was 12.3 weeks with D75 vs 7 weeks with best supportive care (P = .004).


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