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)  or a comparator regimen of chemotherapy (TAX 320)  (Figure
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
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).
1. Fossella FV, Lee JS, Murphy WK, et al: Phase II study of
docetaxel for recurrent or metastatic non-small-cell lung cancer. J Clin Oncol
2. Francis PA, Rigas JR, Kris MG, et al: Phase II trial of
docetaxel in patients with stage III and IV non-small-cell lung cancer. J Clin
Oncol 12:1232-1237, 1994.
3. Cerny T, Kaplan S, Pavlidis N, et al: Docetaxel (Taxotere)
is active in non-small-cell lung cancer: A phase II trial of the EORTC early
clinical trials group (ECTG). Br J Cancer 70:384-387, 1994.
4. Burris HA, Eckardt J, Fields S, et al: Phase II trials of
Taxotere in patients with non-small-cell lung cancer. [abstract] Proc Am Soc
Clin Oncol 12:335a, 1993.
5. Fossella FV, Lee JS, Berille J, et al: Summary of phase II
data of docetaxel (Taxotere), an active agent in the first- and second-line
treatment of advanced non-small-cell lung cancer. Semin Oncol 22(2 suppl
6. Fossella FV, Lee JS, Shin DM, et al: Phase II study of
docetaxel for advanced or metastatic platinum refractory non-small-cell lung
cancer. J Clin Oncol 13:645-651, 1995.
7. Gandara DR, Vokes E, Green M, et al: Activity of docetaxel
in platinum-treated non-small-cell lung cancer: Results of a phase II
multicenter trial. J Clin Oncol 18:131-135, 2000.
8. Robinet G, Kleisbauer JP, Thomas P, et al: Phase II study
of docetaxel (Taxotere) in first- and second-line non-small-cell lung cancer
(abstract 1726). Proc Am Soc Clin Oncol 16:480a, 1997.
9. Shepherd FA, Dancey J, Ramlau R, et al: Prospective
randomized trial of docetaxel vs best supportive care in patients with non-small-cell
lung cancer patients previously treated with platinum-based chemotherapy. J Clin
Oncol 18:2095-2103, 2000.
10. Fossella FV, DeVore R, Kerr RN, et al: Randomized phase
III trial of docetaxel vs vinorelbine or ifosfamide in patients with advanced
non-small-cell lung cancer previously treated with platinum-containing
chemotherapy. J Clin Oncol 18:2354-2362, 2000.
11. Shepherd FA, Fossella FV, Lynch T, et al: Docetaxel (Taxotere)
shows survival and quality-of-life benefits in the second-line treatment of non-small-cell
lung cancer: A review of two phase III trials. Semin Oncol 28(suppl 2):4-9,
12. Fossella FV: Second-line chemotherapy for non-small-cell
lung cancer, in DeVita V, Hellman S, Rosenberg A (eds): Lung Cancer Principles
and Practice Updates 2001 1st ed, vol 1, pp 1-7. New York, Lippincott Williams
& Wilkins; 2001.