Docetaxel plus Oxaliplatin in Combination with Capecitabine as First-Line Treatment for Advanced Gastric Cancer

Amarantidis, Kyriakos; Xenidis, Nikolaos; Chelis, Leonidas; Chamalidou, E.; Dimopoulos, P.; Michailidis, P.; Tentes, Antonios-Apostolos K.; Deftereos, Savas; Karanikas, Michael; Karayiannakis, Anastasios J.; Kakolyris, Stylianos

doi:10.1159/000330199

Cited by 18 publications

(10 citation statements)

References 48 publications

(35 reference statements)

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“…The median OS and PFS times of 11.3 and 6.2 months in patients with good risk TSER genotypes were also comparable to those reported in non-genotype selected populations (Figure 2). Although the observed response rate did not support the utility of TSER genotyping as a treatment selection guide, it should also be noted that the enrolled patients experienced a very promising disease control rate of 95.7% (9 PR and 13 SD out of 23 patients), higher than those reported in the literature [32]–[36]. The high disease control rate in the current study may provide the first prospectively obtained evidence for the utility of TSER genotyping in improving clinical outcomes in patients with gastric and GEJ cancers.…”

Section: Discussioncontrasting

confidence: 68%

Thymidylate Synthase Genotype-Directed Chemotherapy for Patients with Gastric and Gastroesophageal Junction Cancers

Goff

Thakkar

et al. 2014

PLoS ONE

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BackgroundRetrospective studies indicate associations between TSER (thymidylate synthase enhancer region) genotypes and clinical outcomes in patients receiving 5-FU based chemotherapy, but well-controlled prospective validation has been lacking.MethodsIn this phase II study (NCT00515216 registered through ClinicalTrials.gov, http://clinicaltrials.gov/show/NCT00515216), patients with “good risk” TSER genotypes (at least one TSER*2 allele) were treated with FOLFOX chemotherapy to determine whether prospective patient selection can improve overall response rates (ORR) in patients with gastric and gastroesophageal junction (GEJ) cancers, compared with historical outcomes in unselected patients (estimated 43%).ResultsThe ORR in genotype-selected patients was 39.1% (9 partial responses out of 23 evaluable patients, 95% CI, 22.2 to 59.2), not achieving the primary objective of improving ORR. An encouraging disease control rate (DCR, consisting of partial responses and stable diseases) of 95.7% was noted and patients with homozygous TSER*2 genotype showed better tumor response.ConclusionsIn this first prospective, multi-institutional study in patients with gastric or GEJ cancers, selecting patients with at least one TSER*2 allele did not improve the ORR but led to an encouraging DCR. Further studies are needed to investigate the utility of selecting patients homozygous for the TSER*2 allele and additional genomic markers in improving clinical outcomes for patients with gastric and GEJ cancers.Trial RegistrationClinicalTrials.gov NCT00515216

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Section: Discussioncontrasting

confidence: 68%

Thymidylate Synthase Genotype-Directed Chemotherapy for Patients with Gastric and Gastroesophageal Junction Cancers

Goff

Thakkar

et al. 2014

PLoS ONE

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“…In Japan, gastric cancer is one of the most common causes of mortality, despite advances in diagnosis and treatment. In particular, unresectable or recurrent gastric cancer is associated with extremely poor prognosis even when treated with novel therapeutic agents, including taxanes [paclitaxel (2,3) and docetaxel (4,5)], irinotecan (6,7), oxaliplatin (8,9), S-1 (10), and capecitabine (11), which are known to be efficacious in gastric cancer. A multi-center randomized controlled trial (SPIRITS trial) performed in Japan reported that the median overall survival (OS) and progression-free survival in patients with advanced gastric cancer treated with S-1 plus cisplatin were significantly longer in those treated with S-1 alone (10).…”

Section: Introductionmentioning

confidence: 99%

Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer

Masuzawa

Fujiwara

Okada

et al. 2012

International Journal of Oncology

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Abstract. The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 combined with chemotherapy in patients with advanced gastric cancer. HLA-A * 2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1-1084 and VEGFR2-169 combined with S-1 and cisplatin. The study included 22 patients (median age 60.5 years) who received at least one cycle of the combination therapy. No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients. Twelve patients (55%) showed partial response and 10 had stable disease after two cycles of the combination therapy. The disease control rate (partial response and stable disease) was 100% after two cycles. The median time to progression was 9.6 months and median overall survival was 14.2 months. VEGFR1-1084-specific cytotoxic T lymphocyte (CTL) response was induced in 18 (82%) of the 22 patients and VEGFR2-169-specific CTL response was induced in 18 (82%) of the 22 patients. Patients showing CTL response to VEGFR2-169 peptide had significantly better prognosis than those without, as demonstrated by the overall survival (OS) and time to progression (TTP) (OS, p=0.028, TTP, p=0.006). The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer. Substantial specific CTL for both peptides was frequently induced even under chemotherapy. Thus, cancer vaccination combined with standard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer.

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“…A 3-week DOX regimen consisting of docetaxel at 60 mg/m 2 and oxaliplatin at 100 mg/ m 2 on day 1 and continuous orally administered capecitabine at 1000 mg/m 2 daily yielded an ORR of 52.1 %, a median PFS of 6.9 months, and a median OS of 12.6 months [18]. When docetaxel at 50 mg/m 2 and oxaliplatin at 75 mg/m 2 were administered intravenously on day 1, and capecitabine at 2750 mg/m 2 was administered orally on days 1-7 every 2 weeks, the ORR, median TTP, and median OS were 59 %, 10.0 months, and 18.0 months, respectively [19]. Considering also our study, docetaxelcontaining triplet regimens demonstrated better treatment outcomes compared with those for doublets including platinum and fluoropyrimidine.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer

et al. 2015

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Background Although the docetaxel, 5-fluorouracil, and cisplatin triplet has yielded significant improvements in time to progression, overall survival, and overall response rate, the high incidence of severe adverse events limits the use of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this limitation, we evaluated the efficacy and safety of the combination of docetaxel, oxaliplatin, and S-1 for the treatment of metastatic gastric cancer. Methods Chemotherapy-naive patients with pathologically proven unresectable recurrent or metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at 52.5 mg/m 2 and oxaliplatin at 105 mg/m 2 were administered intravenously on day 1, and S-1 was administered orally at 80 mg/m 2 on days 1-14 of every 21-day cycle.Results Forty-four patients (median age 54.5 years) were enrolled. All patients had metastatic disease. A total of 340 cycles of chemotherapy were administered (median of eight cycles per patient; range 1-36 cycles). Toxicities were evaluated in 43 patients, and the responses were evaluated in 40 patients. Major toxicities included grade 3/4 neutropenia (37.2 %) and leukopenia (27.9 %). The overall response rate was 54.5 % [95 % confidence interval (CI) 40.1-68.3 %] in the intention-to-treat population. The median progression-free survival and overall survival were 7.6 months (95 % CI 6.2-9.0 months) and 12.0 months (95 % CI 6.9-17.2 months), respectively. Conclusion These data suggest that the docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively well tolerable, and it seems to have potential to be a reasonable therapeutic strategy in patients with metastatic or recurrent gastric cancer.

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Docetaxel plus Oxaliplatin in Combination with Capecitabine as First-Line Treatment for Advanced Gastric Cancer

Cited by 18 publications

References 48 publications

Thymidylate Synthase Genotype-Directed Chemotherapy for Patients with Gastric and Gastroesophageal Junction Cancers

Thymidylate Synthase Genotype-Directed Chemotherapy for Patients with Gastric and Gastroesophageal Junction Cancers

Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer

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