Phase II study of a fixed dose-rate infusion of gemcitabine associated with docetaxel in advanced non-small-cell lung carcinoma

Abstract

Prolonged gemcitabine infusion combined with docetaxel is well tolerated and its efficacy is similar to that of other chemotherapeutic schemes used for NSCLC treatment. However, the prolonged infusion of gemcitabine did not appear to result in any improvement in outcome or toxicity versus the standard dose rate.

Gemcitabine administered as a short infusion versus a fixed dose rate in combination with cisplatin for the treatment of patients with advanced non-small cell lung cancer

“…While gemcitabine is most commonly administered over a 30-min infusion, there is evidence to suggest that a prolonged FDR infusion may be more pharmacologically efficient [10,12,13] and the latter has shown promising results in phases I and II clinical trials for the treatment of NSCLC and pancreatic adenocarcinoma [11,[14][15][16][17].…”

“…Phase II trials investigating the FDR gemcitabine infusion (10 mg/m 2 /min) in NSCLC have demonstrated promising efficacy with response rates ranging from 26% to 41% and median overall survival ranging from 7 to 13 months [14][15][16][17]. In these trials, the main toxicities that were more common with a prolonged infusion time were haematological, especially neutropenia and thrombocytopenia, however, it was usually reported that the FDR infusion had a manageable toxicity profile that was not dissimilar to that observed with the standard 30-min gemcitabine infusion.…”

Intra-patient alternated dose escalation of paclitaxel and gemcitabine versus paclitaxel followed by fixed dose rate infusion of gemcitabine in fit elderly non-small cell lung cancer patients

“…De Castro et al assessed the FDR infusion of gemcitabine 1000 mg/m 2 on days 1 and 8, together with docetaxel 75 mg/m 2 on day 8, every 3 weeks in 50 NSCLC patients (60% in stage IV). In this trial, median PFS was 4 months, median and 1-year was 7 months and 25%, respectively, but it should be noted that 30% of patients were in ECOG PS 2 [27].…”

“…This customized approach according to the individual tolerability of each patient allowed to safely reach the optimal dosages of both drugs in half of the treated series [13]. On the other hand, the FDR infusion of gemcitabine is supported by early clinical evidences [19,20], and some pilot trials in NSCLC patients, assessing this modality of delivery either alone [22][23][24] or in combination with other active drugs [24][25][26][27]. Therefore, the present study was undertaken to ascertain which schedule of the combination of paclitaxel and gemcitabine, i.e., the intra-patient dose escalation, or the FDR of gemcitabine, could produce the longer FFS.…”

“…Moreover, the FDR was significantly more effective, although also slightly more toxic, than the shorter infusion, in patients with advanced or metastatic pancreatic cancer [21]. This observation prompted several researchers to asses the FDR infusion of gemcitabine, either alone [22,23] or in combination with other active drugs for the treatment of patients with NSCLC [24][25][26][27].…”