Weekly low-dose docetaxel in advanced non-small cell lung cancer previously treated with two chemotherapy regimens
Introduction
Most patients with advanced non-small cell lung cancer (NSCLC) undergo chemotherapy in an attempt to prolong survival or relieve symptoms [1]. One of the most widely accepted first-line therapies in advanced NSCLC is combination chemotherapy based on cisplatin, which leads to response rates of 30–40% and a median survival of 8–10 months [2].
The role of second-line chemotherapy is still controversial, but the recent development of a number of active antineoplastic agents (vinorelbine, gemcitabine, docetaxel, irinotecan) has created new possibilities for disease management. Vinorelbine has led to objective response rates of up to 37% and median survivals ranging from 33 to 40 weeks as first-line treatment, and has often been used, alone or in combination, as salvage chemotherapy [3], [4]. Gemcitabine is an analogue of the pyrimidine antimetabolite cytarabine that has shown interesting results (a 19% response rate as second-line treatment in advanced NSCLC), and irinotecan is a topoisomerase I inhibitor that has also been found to have some activity in a second-line setting [5], [6].
It has been reported that the taxanes (docetaxel and paclitaxel) are among the most promising single agents, and docetaxel in particular has gained the reputation of being one of the most effective drugs for the treatment of NSCLC. In previously untreated patients with advanced NSCLC, single-agent docetaxel at doses of 60, 75 or 100 mg/m2 administered once every 3 weeks has led to objective response rates of approximately 30% [7], [8]. A number of studies have shown that it is active in patients previously treated with platinum-based regimens, with 18–23% of objective responses, and that its dose-limiting toxicities are leukopenia, peripheral neuropathy and fluid retention [8], [9], [10]. Moreover, the weekly administration of docetaxel seems to achieve similar results than the 3-weekly schedule with good tolerability [11]. Although docetaxel is one of the most widely used drugs in a second-line setting, no standard option exists and advanced NSCLC patients often receive non-taxane-based chemotherapy as salvage treatment.
The aim of this study was to evaluate the activity and safety of weekly docetaxel in patients with advanced NSCLC cancer previously treated with two chemotherapy regimens.
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Eligibility criteria
The study involved patients with histologically documented stage IIIB, IV or recurrent metastatic NSCLC previously treated with two non-taxane-based chemotherapy regimens. All of them had uni- or bi-dimensionally measurable disease by chest radiography or computed tomography (CT). Although histological confirmation was highly encouraged, hilar or mediastinal lymph nodes with a short-axis diameter of more than 1-cm were considered tumoral. The target lesion had to be outside any previous
Results
Table 1 shows the characteristics of the 26 patients, who were enrolled between September 1999 and August 2001. Their median age was 66 years (14 patients were older than 65 years). All were ambulatory, but 9 (35%) had an ECOG PS of 2. Fourteen patients (54%) had distant metastases; in the remaining 12 (46%), the disease was localised to the chest. All of the patients had received cisplatin- or carboplatin-based chemotherapy as first-line treatment; the second-line chemotherapies were
Discussion
The availability of new drugs with a favourable toxicity profile and innovative, non-overlapping mechanisms of action is currently increasing the possibility of re-evaluating the role of salvage treatment in patients with advanced NSCLC who have failed on platinum-based chemotherapy.
The results of this study provide evidence of the activity and safety of weekly low-dose docetaxel in patients with advanced NSCLC previously exposed to two chemotherapy regimens. The response rate in our population
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