Cisplatin and vinorelbine as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) resistant to taxol plus gemcitabine
Introduction
First-line Cisplatin (CDDP)-based polichemotherapy prolongs survival and improves quality of life in patients with advanced non-small cell lung cancer (NSCLC) [1]. To our knowledge, no studies have tested the activity of CDDP-based regimens as second-line chemotherapy (CT) in patients with NSCLC resistant to a first-line combination of new drugs not containing CDDP.
Cisplatin plus vinorelbine (VNR) is an active combination in patients with advanced NSCLC, with a response-rate as first-line treatment ranging between 26 and 43% in randomized studies [2], [3], [4], [5].
Between November 1997 and March 1999, we treated 35 chemo-naive patients with advanced NSCLC in a dose-escalation study with paclitaxel (TAX) plus Gemcitabine (GEM) given weekly [6]. In the present study we analysed the outcome of 17 of these patients that were successively treated with CDDP plus VNR at the time of progression.
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Patients and methods
Seventeen patients with advanced NSCLC resistant to weekly TAX and GEM were treated in our institute with CDDP plus VNR as second-line chemotherapy. Three patients received external radiotherapy after first-line CT on non-parameter sites (mediastinum, two patients; bone, one patient). We considered refractory to the previous treatment patients with progressive disease while receiving CT and patients with no disease response after receiving a minimum of two cycles of CT [7]. Treatment consisted
Results
Between June 1998 and September 1999, 17 patients with advanced NSCLC were treated with a second-line CT with CDDP plus VNR. All patients progressed after TAX plus GEM given weekly, administered as first-line CT in a previous dose-escalation study. The median interval between the last course of first-line CT and the first course of second-line CT in sensitive cancers was 17 weeks (range: 4–34 weeks). Patients characteristics are reported in Table 1.
Eight patients were considered refractory to
Discussion
We treated with Cisplatin (CDDP) plus Vinorelbine (VNR) 17 patients with NSCLC progressing after a first-line chemotherapy with paclitaxel (TAX) plus Gemcitabine (GCB). Three patients achieved a partial response (18%, 95% CI: 4–43%), four had stable disease and 10 had disease progression. All responses were observed among the nine patients that achieved a PR maintained at least until the end of the prior treatment. Time to progression of the responders was 16+, 28 and 50 weeks.
At a median
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Outcome of advanced nonsmall cell lung cancer patients receiving gemcitabine and weekly paclitaxel as first-line treatment
2008, Lung CancerCitation Excerpt :Although multiple studies had proved the therapeutic roles of various second-line chemotherapy in NSCLC patients with prior platinum treatment [27] the reverse sequence of drug administration is rarely reported. A combination of vinorelbine and cisplatin was used in two studies [28,29] for advanced NSCLC patients pretreated with taxane-based regimens, and was reported to achieve response rates of 18% and 19%. The median survivals after vinorelbine–cisplatin treatment were 8.8 and 7.6 months, respectively.
A systematic review of platinum and taxane resistance from bench to clinic: An inverse relationship
2007, Cancer Treatment ReviewsCitation Excerpt :The most common carcinoma examined is ovarian, where the majority of patients have failed combination platinum/taxane therapy.213,214,186,215 There are several studies which have platinum-naïve patients receiving platinum salvage after taxane therapy216–218 but there are not enough studies from a single type of carcinoma to pool data to allow comparisons to be made. From the systematic review of resistant cell models it appears that the observed inverse relationship between platinums and taxanes is independent of the currently known major mechanisms of resistance to both agents.