Weekly Docetaxel with or without Gemcitabine as Second-Line Chemotherapy in Paclitaxel-Pretreated Patients with Metastatic Breast Cancer: A Randomized Phase II Study Conducted by the Hellenic Co-Operative Oncology Group

Abstract

Objective: A randomized phase II trial was conducted to test whether the addition of gemcitabine to weekly docetaxel could improve the objective response rate and survival outcomes as second-line chemotherapy in patients with metastatic breast cancer who have failed a paclitaxel-containing regimen. Methods: Patients were randomized to receive either weekly docetaxel 40 mg/m² (group A, n = 34) or the combination of weekly docetaxel 35 mg/m² with gemcitabine 600 mg/m² (group B, n = 41). Three consecutive weekly infusions followed by a 1-week rest period represented 1 chemotherapy cycle. Results: The objective response rate was 18% and 27.5% in group A and B, respectively (p = 0.413). No statistically significant differences were demonstrated in terms of median overall survival and time to disease progression. The rate and grade 3 and 4 neutropenia were higher in group B (23 vs. 3%). Conclusions: The weekly administration of docetaxel and gemcitabine did not result in superior clinical outcomes over weekly docetaxel.

A systematic review of gemcitabine and taxanes combination therapy randomized trials for metastatic breast cancer

“…Taxanes is good combination agent with gemcitabine, including paclitaxel and docetaxel.To define the combination regimen including gemcitabine in MBC, physicians have conducted phase III clinical trials to compare the efficacy and toxicity between regimens MBC (Albain et al 2008 ; Chan et al 2009 ; Joensuu et al 2010 ; Zielinski et al 2005 ; Levy & Fumoleau 2005 ; Brufsky et al 2011 ; Nielsen et al 2011 ; Papadimitriou et al 2009 ).The combination of gemcitabine/taxanes-based(GT-based) combination is an effective regimen that is well tolerated with good response rates (Gudena et al 2008 ). Previous studies have demonstrated that GT-based regimen has a clinically meaningful benefit (Joensuu et al 2010 ; Nielsen et al 2011 ; Papadimitriou et al 2009 ). However, other data showed that the gemcitabine addition of taxanes was not associated with a statistically significant improvement in OR and TTP but did lead to increased toxicity (Joensuu et al 2010 ; Nielsen et al 2011 ; Papadimitriou et al 2009 ).…”

Second-line single-agent chemotherapy in human epidermal growth factor receptor 2-negative metastatic breast cancer: A systematic review

“…A PRISMA flow diagram of the citation screening for the original and updated SRs is shown in Table 1 categorises included RCTs by treatment line, including key trial characteristics. Of the 14 second-and/or later-line papers, five [19][20][21][22][23] reported data for a purely second-line patient population, three [24][25][26] reported data from mixed-line treatment but provided results for the second-line subgroup separately, three [27][28][29] had unclear second-line status (i.e. it was unclear whether the previous therapy had been given in the adjuvant or metastatic setting), two [30,31] reported data from second-or later-line patients, and one [32] reported data from a second-or later-line subgroup separately.…”

“…The primary endpoint was OS in two trials [26,30], PFS in four [19,27,29,31], overall response in three [23,28,32] and not reported in five papers published between 1990 and 2000 [20-22, 24, 25] ( Table 1). Safety/toxicity was typically a secondary endpoint, amongst others.…”

“…Only one trial was double-blinded [29] and almost all trials did not have blinded outcome assessors. In terms of the distribution of patient characteristics between treatment groups, slight imbalances in potential prognostic factors were noted in six trials [20][21][22][23][24]29]. Few trials reported confidence intervals around point estimates and only three confirmed HER2-negative status at enrolment.…”

Efficacy of gemcitabine-based chemotherapy in metastatic breast cancer: a meta-analysis of randomized controlled trials

“…Four trials were excluded [8][9][10][11] , namely, a phase III trial using a three-arm design, two phase III trials without a gemcitabine-free control arm and a phase II trial without sufficient data. A total of nine trials met the inclusion criteria in this metaanalysis [12][13][14][15][16][17][18][19][20] , from which 2651 patients were included in the assessment for overall response and toxicity.…”