Chemotherapy of advanced gastric cancer

Rivera, Fernando; Vega-Villegas, M. E.; López‐Brea, Marta

doi:10.1016/j.ctrv.2007.01.004

Cited by 123 publications

(99 citation statements)

References 56 publications

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“…Recently, oxaliplatin, a third-generation platinum compound, and 5-FU combination regimens have demonstrated comparable efficacy with more favorable toxicity profiles compared to 5-FU and cisplatin-based regimens [3,4,[7][8][9][10]. However, despite the availability of various effective chemotherapy regimens, the overall outcome of advanced gastric cancer is still very poor, with median survival of 6-11 months [2][3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Palliative chemotherapy is the standard of care in patients with unresectable or metastatic or recurrent disease with some improvement of survival and quality of life [2][3][4][5][6]. Although there is no standard regimen in palliative chemotherapy for gastric cancer, cisplatin and 5-fluorouracil (5-FU)-based regimens, with or without another agent, have been used the most frequently [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…The overall outcome of gastric cancer is still unsatisfactory, because many patients present with unresectable or metastatic disease, while the recurrence is quite common even after radical resection, which is the only curative treatment [2][3][4][5][6]. Palliative chemotherapy is the standard of care in patients with unresectable or metastatic or recurrent disease with some improvement of survival and quality of life [2][3][4][5][6]. Although there is no standard regimen in palliative chemotherapy for gastric cancer, cisplatin and 5-fluorouracil (5-FU)-based regimens, with or without another agent, have been used the most frequently [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Bax Predicts Outcome in Gastric Cancer Patients Treated with 5-fluorouracil, Leucovorin, and Oxaliplatin Palliative Chemotherapy

et al. 2010

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Background Platinum and 5-fluorouracil (5-FU)-based regimens have been used the most frequently in palliative chemotherapy for gastric cancer. The present study evaluated the prognostic significance of Bax, excision repair cross-complementation group 1 (ERCC1), and thymidylate synthase (TS) in advanced gastric cancer patients treated with 5-FU, leucovorin, and oxaliplatin (FOLFOX) palliative chemotherapy. Methods Seventy-two patients with metastatic or recurrent gastric cancer were treated with FOLFOX regimen. Pretreatment tumor biopsy specimens were analyzed for Bax, ERCC1, and TS expression by immunohistochemistry.Results High expression of Bax, ERCC1, and TS was observed in 31 (43%), 33 (46%), and 35 (49%) patients, respectively. The median overall survival (OS) of patients was 12 months. Low expression of Bax was associated with poor OS (median, 9 months vs. 18 months; 2-year, 10% vs. 48%; p = 0.0005) in univariate analysis, while expression of ERCC1 and TS was not correlated with patient outcome. In multivariate analysis, low expression of Bax was a significant independent predictor of poor OS (p = 0.028). Low expression of Bax was significantly associated with poor survival of patients with metastatic or recurrent gastric cancer treated with FOLFOX chemotherapy. Conclusions Immunohistochemical staining for Bax with pretreatment biopsy specimen may be useful in selecting FOLFOX regimen as a treatment option for advanced gastric cancer patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bax Predicts Outcome in Gastric Cancer Patients Treated with 5-fluorouracil, Leucovorin, and Oxaliplatin Palliative Chemotherapy

et al. 2010

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“…(1)(2)(3)(4)(5) Much is known about the drug's metabolism and pharmacokinetics. Irinotecan's hydrolysis by the high affinity carboxylesterase-2 (CES-2) is responsible for activation of irinotecan to SN-38 (7-ethyl-10-hydroxycamptothecin), a potent topoisomerase I inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetic Pathway Analysis of Irinotecan

Rosner

Panetta

Innocenti

et al. 2008

Clin Pharmacol Ther

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Irinotecan, a chemotherapeutic agent for various solid tumors, is a prodrug requiring activation to SN-38. Irinotecan's complex pharmacokinetics allows for potentially many genetic sources of variability. We explored relationships between pharmacokinetic pathways and polymorphisms in genes associated with irinotecan's metabolism and transport. We fit a seven-compartment pharmacokinetic model with enterohepatic recirculation to concentrations of irinotecan and metabolites SN-38, SN-38G (glucuronide), and APC. Principal component analysis (PCA) of patientspecific parameter estimates produced measures interpretable along pathways. Nine principal components characterized overall variation well. Polymorphisms in genes UGT1A1, UGT1A7, and UGT1A9 had strong associations with a component corresponding to the irinotecan-to-SN-38 pathway and SN-38 recirculation and to a component relating to SN-38-to-SN-38G conversion and SN-38G's elimination. The component characterizing irinotecan's compartments was associated with HNF1α and ABCC2 polymorphisms. The exploratory analysis with PCA in this pharmacogenetic analysis identified known associations and may have allowed identification of previously uncharacterized functional polymorphisms.

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“…The incorporation of these agents in new combinations has resulted in regimens such as DCF (docetaxel, cisplatin, fluorouracil), EOX (epirubicin, oxaliplatin, capecitabine) and ILF (irinotecan, leucovorin, fluorouracil), which could have a role in the treatment of these patients but survival is still very poor (Rivera et al, 2007). Recently, the combination of irinotecan and oxaliplatin showed activity in advanced gastric cancer with a 50% response rate (RR) and a favourable toxicity profile in 32 patients (Souglakos et al, 2004).…”

mentioning

confidence: 99%

Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma

Lauro¹,

Nunziata

Arena

et al. 2007

Br J Cancer

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This phase II study was designed to evaluate the activity and safety of a combination of irinotecan, docetaxel and oxaliplatin in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Forty patients with measurable distant metastasis received irinotecan 150 mg m À2 and docetaxel 60 mg m À2 on day 1, and oxaliplatin 85 mg m À2 on day 2. Cycles were repeated every 3 weeks. The primary end point was to demonstrate a 50% improvement in time-to-progression (TTP) over historical controls. All patients were evaluable. Median TTP was 6.5 months (95% confidence interval (CI) 5.6 -7.4), the overall response rate was 50% (95% CI 35 -65%) and the median overall survival was 11.5 months (95% CI 8.7 -14.3). Grade 3/4 neutropaenia occurred in 47.5% of patients. There were four episodes of febrile neutropaenia in three patients. Other non-haematological grade 3 toxicities included diarrhoea in four patients (10%), vomiting in three patients (7.5%) and mucositis in two patients (5%). The irinotecan, docetaxel and oxaliplatin combination chemotherapy is an active and well-tolerated novel regimen for treating metastatic gastric or GEJ adenocarcinoma and deserves further evaluation in randomised trials and in combination with molecular targeting agents.

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Chemotherapy of advanced gastric cancer

Cited by 123 publications

References 56 publications

Bax Predicts Outcome in Gastric Cancer Patients Treated with 5-fluorouracil, Leucovorin, and Oxaliplatin Palliative Chemotherapy

Bax Predicts Outcome in Gastric Cancer Patients Treated with 5-fluorouracil, Leucovorin, and Oxaliplatin Palliative Chemotherapy

Pharmacogenetic Pathway Analysis of Irinotecan

Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma

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