Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study

Cutsem, Éric Van; Boni, C.; Tabernero, Josep; Massutí, Bartomeu; Middleton, Gary; Dane, Faysal; Reichardt, Peter; Pimentel, Francisco; Cohn, Allen Lee; Follana, Philippe; Clemens, Michael; Zaniboni, Alberto; Moiseyenko, Vladimir; Harrison, Mark; Richards, Donald A.; Prenen, Hans; Pernot, Simon; Ecstein-Fraïsse, Evelyne; Hitier, Simon; Rougier, Philippe

doi:10.1093/annonc/mdu496

Cited by 103 publications

(89 citation statements)

References 22 publications

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“…In addition, a recent study has reported that combination chemotherapy comprising docetaxel (60 mg/m (from 14 to 7 days) plus docetaxel and oxaliplatin offered comparable efficacy against advanced gastric cancer with tolerable side-effects. In the present study, the effective rate of the DOX regimen was 75%, an outcome similar to that of earlier clinical trials using these drug combinations (23)(24)(25)(26), in which the median time to progression and median OS were not inferior to those achieved by the DCF regimen. However, overall clinical outcome for patients treated with the DOX regimen determined by the present study should be evaluated in a phase-II trial to compare it with that for patients treated with other DOX regimens or the conventional DCF regimen.…”

Section: Discussionsupporting

confidence: 89%

Seven-day capecitabine plus docetaxel and oxaliplatin regimen for the treatment of advanced gastric cancer: A phase-I clinical trial

Liang

et al. 2017

Molecular and Clinical Oncology

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Abstract. Docetaxel, cisplatin and 5-fluorouracil (DCF regimen) are currently applied as an effective combination treatment for various human malignancies; however, the efficacy of this regimen is impaired by severe adverse events associated with it. Therefore, better-tolerated regimens with comparable efficiency are required for patients with gastric cancer. To explore such possibilities, a phase-I clinical trial was performed to evaluate the safety and tolerability of a modified regimen replacing cisplatin and 5-fluorouracil with oxaliplatin and capecitabine, respectively (DOX program). The maximum-tolerated dose (MTD) and dose-limited toxicity (DLT) of capecitabine in this regimen were determined and a dose for subsequent phase-II clinical trials was identified. A total of 24 patients with advanced gastric cancer were sequentially enrolled in the present capecitabine dose-escalation trial. The patients were treated with docetaxel and oxaliplatin at fixed doses [75 and 100 mg/m 2 , respectively, intravenously, on day 1 (d 1 )], and with capecitabine at increasing doses (1,500, 2,000 and 2,500 mg/m 2 , per os, d 1-7 ). The MTD of capecitabine was 2,000 mg/m 2 (d 1-7 ), repeated every 21 days for at least two cycles. The most frequent DLTs for this regimen were leukopenia (15/24, 62.5%, all at grade-III/IV) and neutropenia (13/24, 54.2%, all at grade-III/IV), nausea (14/24, 58.3%, all at grade-III) and vomiting (13/24, 54.2%, all at grade-III). The effective rate of the DOX regimen was 75.0% (18/24). Based on the results, the combination of docetaxel (75 mg/m 2 , d 1 ), oxaliplatin (100 mg/m 2 , d 1 ) and capecitabine (2,000 mg/m 2 , d 1-7 ) is recommended for a future phase-II trial. While these doses for the DOX regimen were generally well tolerated, the efficacy of this modified regimen in patients with advanced gastric cancer remains to be further evaluated in subsequent phase-II trials. IntroductionThe combination of docetaxel, cisplatin and 5-fluorouracil (DCF regimen) is currently used to treat human malignant diseases, including various progressive head and neck squamous cell carcinomas and advanced gastric and esophageal cancers (1,2). However, a high incidence of grade III/IV adverse events (AEs) resulting from these compounds works against the therapeutic efficacy of the DCF program (3). Therefore, optimizing the conventional DCF program may lead to a comparable efficacy, but with lower toxicity.The oral anti-cancer precursor molecule, capecitabine, is metabolized to 5-fluorouracil by thymidine phosphorylase (TP) in tumor cells, and its efficacy has been established in multiple clinical trials (4). It is more effective than (or at least not inferior to) 5-fluorouracil against a variety of malignant solid tumor types (5). Therefore, capecitabine may be ideal for replacing intravenous 5-fluorouracil. Oxaliplatin is a third-generation, platinum-containing anti-cancer drug and several clinical studies have reported that the one-year survival rate of patients who had received an anti-cancer regimen contain...

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Section: Discussionsupporting

confidence: 89%

Seven-day capecitabine plus docetaxel and oxaliplatin regimen for the treatment of advanced gastric cancer: A phase-I clinical trial

Liang

et al. 2017

Molecular and Clinical Oncology

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“…The FLOT regimen (fluorouracil, leucovorin, oxaliplatin and docetaxel) resulted in a median PFS of 5.1 months and a median OS of 11 months in a small non-randomised study [63]. An almost identical regimen used in a randomised phase II trial resulted in encouraging median PFS and OS of 7.7 and 14.6 months, respectively [II, B] [64]. As an alternative to platinum-based therapy, irinotecan plus leucovorin and infusional 5-FU (FOLFIRI) has been studied in both phase II trials and one phase III randomised trial in the first-line setting, and may be considered for selected patients [60,65].…”

Section: Perioperative Chemotherapymentioning

confidence: 99%

Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

et al. 2016

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“…It showed that median OS of DCF was significantly longer than CF (9.2 months vs. 8.6 months; P = 0.02), but DCF produced more toxicity [38,39] . Several modified DCF regimens demonstrated the efficacy and the safety [40][41][42] . Thus, the original DCF is not recommended, and modified DCF is still one of the option in specific cases.…”

Section: First Line Therapymentioning

confidence: 99%

Recent trend in gastric cancer treatment in the USA

Harada

Baba

Ajani

2018

JCMT

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Gastric adenocarcinoma (GAC) is estimated as the fifteenth most common cancer in the USA. Incidence rate has been gradually decreasing, but prognosis remains dismal. For patients with locally advanced GAC (stage > T1B and < T4B), multimodality therapies, such as surgery, chemotherapy, and radiation therapy, are needed. Perioperative chemotherapy or postoperative chemoradiation/chemotherapy is recommended. For metastatic GAC patients, combination of two cytotoxics (platinum compound and fluoropyrimidine) has become a common place in the USA, and when HER2 is positive, trastuzumab is added. When GAC progresses after the first line therapy, additional biomarkers (microsatellite instability and programmed death ligand 1) should be tested so that checkpoint inhibitors can be used. Overall, the options for advanced GAC patients are limited and more research is needed.

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Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study

Abstract: These results suggest that TEF is worthy of evaluation as an arm in a phase III trial or as a backbone regimen for new targeted agents in advanced GC. CLINICALTRIALS.GOV: Identifier Trial registration number: NCT00382720.

Cited by 103 publications

References 22 publications

Seven-day capecitabine plus docetaxel and oxaliplatin regimen for the treatment of advanced gastric cancer: A phase-I clinical trial

Seven-day capecitabine plus docetaxel and oxaliplatin regimen for the treatment of advanced gastric cancer: A phase-I clinical trial

Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Recent trend in gastric cancer treatment in the USA

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