Docetaxel, Cisplatin and Fluorouracil (DCF) Regimen Compared with Non-Taxane-Containing Palliative Chemotherapy for Gastric Carcinoma: A Systematic Review and Meta-Analysis

Abstract

BackgroundGastric carcinoma (GC) is one of the highest cancer-mortality diseases with a high incidence rate in Asia. For surgically unfit but medically fit patients, palliative chemotherapy is the main treatment. The chemotherapy regimen of docetaxel, cisplatin and 5-fluorouracil (DCF) has been used to treat the advanced stage or metastatic GC. It is necessary to compare effectiveness and toxicities of DCF regimen with non-taxane-containing palliative chemotherapy for GC.MethodsPubMed, EmBase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases were searched to select relative randomized controlled trials (RCTs) comparing DCF to non-taxane-containing chemotherapy for patients with palliatively resected, unresectable, recurrent or metastatic GC. Primary outcome measures were 1-year and 2-year overall survival (OS) rates. Secondary outcome measures were median survival time (MST), median time to progression (TTP), response rate and toxicities.ResultsTwelve RCTs were eligible and 1089 patients were analyzed totally (549 in DCF and 540 in control). DCF regimen increased partial response rate (38.8% vs 27.9%, p = 0.0003) and reduced progressive disease rate (18.9% vs 33.3%, p = 0.0005) compared to control regimen. Significant improvement of 2-year OS rate was found in DCF regimen (RR = 2.03, p = 0.006), but not of 1-year OS rate (RR = 1.22, p = 0.08). MST was significantly prolonged by DCF regimen (p = 0.039), but not median TTP (p = 0.054). Both 1-year OS rate and median TTP had a trend of prolongation by DCF regimen. Chemotherapy-related mortality was comparable (RR = 1.23, p = 0.49) in both regimens. In grade I-IV toxicities, DCF regimen showed a major raise of febrile neutropenia (RR = 2.33, p<0.0001) and minor raises of leucopenia (RR = 1.25, p<0.00001), neutropenia (RR = 1.19, p<0.00001), and diarrhea (RR = 1.59, p<0.00001), while in other toxicities there were no significant differences.ConclusionDCF regimen has better response than non-taxane containing regimen and could potentially improve the survival outcomes. The chemotherapy-related toxicity of DCF regimen is acceptable to some extent.

Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry

“…It is interesting to emphasize that the REAL-2 phase III clinical trial that led to the generalization of EOX in AGC confirmed the non-inferiority hypothesis for oxaliplatin and capecitabine versus cisplatin and fluorouracil; however, the study was not designed to appraise the value of adding epirubicin, since the four treatment arms included anthracycline [24]. The role of adding anthracyclines to platinum and fluoropyrimidine-based schedules is even more controversial if we consider that docetaxel-containing triplets have demonstrated their superiority to doublets not containing docetaxel in a multicenter, phase III study [25] and have achieved an increase in responses and a trend toward greater survival rates in a meta-analysis that included 12 RCTs [26]. Likewise, triplets with docetaxel have displayed a trend toward superiority over triplets with anthracyclines (NCT02445209) [27].…”

Impact of the availability of active cytotoxic agents on the survival of patients with advanced gastric cancer

“…Due to the non-inferior efficacy, oxaliplatin may be substituted for cisplatin in the treatment of AGC, and elderly patients may derive a particular benefit from treatment with oxaliplatin instead of cisplatin (10,14). Taxanes, such as docetaxel or paclitaxel, which bind and stabilize microtubules and therefore lead to cell-cycle arrest, have also been used as a first-line therapy for AGC (15,16). In addition, irinotecan has been reported to demonstrate activity in gastrointestinal cancers, and irinotecan-based combination regimens have been studied as a first-line alternative to platinum-based chemotherapy (17,18).…”

“…However, if sequential treatment with all active cytotoxic agents cannot be guaranteed for 100% of the patients, the use of a triplet combination protocol may be considered as first-line therapy. The safety and efficacy of this approach has been assessed in previous clinical trials (15,16). Triplet combination chemotherapy comprising an anthracycline or a taxane in addition to fluoropyrimidine and platinum compounds has resulted in higher response rates and a modest improvement in overall survival compared with doublet combinations (6).…”

Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic gastric cancer

“…The pretreatment characteristics of patients are listed in Table 1. None of the patients had previously received chemotherapy for advanced disease; 9 patients had received adjuvant chemotherapy without docetaxel or oxaliplatin with a median disease-free interval of 12 months (range, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] (Figs. 1, 2).…”

“…The incorporation of docetaxel to cisplatin/fluorouracil chemotherapy (DCF) showed superiority over cisplatin/fluorouracil in a randomized phase III trial [8]. Furthermore, in a recent meta-analysis the use of DCF was correlated with a higher response rate than non-taxanes-containing regimens [13]. Nevertheless, the widespread use of DCF was hindered by severe toxicity, such as neutropenic infections and febrile neutropenia.…”