A phase II trial of biweekly high dose gemcitabine for patients with metastatic pancreatic adenocarcinoma

Ulrich‐Pur, Herbert; Kornek, Gabriela; Raderer, Markus; Haider, Karin; Kwasny, Werner; Depisch, D.; Greul, Rosemarie; Schneeweiß, Bruno; Krauss, G.; Funovics, J.; Scheithauer, Werner

doi:10.1002/1097-0142(20000601)88:11<2505::aid-cncr11>3.0.co;2-e

Cited by 43 publications

(24 citation statements)

References 20 publications

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“…One way to begin to broaden our understanding of gemcitabine metabolism is to examine the genetic differences in the metabolic enzymes, potentially explaining differences in response to gemcitabine. [2][3][4][5][6][7] Currently, there is a focus on analyzing individual genes that may be involved in drug metabolism. It is unlikely that a single gene will be the key to understanding inter-patient variability.…”

Section: Introductionmentioning

confidence: 76%

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Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway

et al. 2004

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Significant variability in the antitumor efficacy and systemic toxicity of gemcitabine has been observed in cancer patients. However, there are currently no tools for prospective identification of patients at risk for untoward events. This study has identified and validated single-nucleotide polymorphisms (SNP) in genes involved in gemcitabine metabolism and transport. Database mining was conducted to identify SNPs in 14 genes involved in gemcitabine metabolism. Pyrosequencing was utilized to determine the SNP allele frequencies in genomic DNA from European and African populations (n ¼ 190). A total of 14 genetic variants (including 12 SNPs) were identified in eight of the gemcitabine metabolic pathway genes. The majority of the database variants were observed in population samples. Nine of the 14 (64%) polymorphisms analyzed have allele frequencies that were found to be significantly different between the European and African populations (Po0.05). This study provides the first step to identify markers for predicting variability in gemcitabine response and toxicity.

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Section: Introductionmentioning

confidence: 76%

“…[1][2][3][4][5][6][7] Gemcitabine has a complex metabolic pathway ( Figure 1). [8][9][10] There are many mechanisms that can contribute to gemcitabine cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway

et al. 2004

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“…It was effective in controlling cancer-related symptoms, but still led to a low rate of objective responses, and did not affect the median patient survival in comparison with 5-FU alone (Burris et al, 1997). Further studies testing different schedule of GEM administration (Ulrich-Pur et al, 2000) or combination of GEM with other drugs such as 5-FU (Schulz et al, 1998;Berlin et al, 1998Berlin et al, -99, 2002Cascinu et al, 1999;Hidalgo et al, 1999;Cohen et al, 2002;Heinemann et al, 2000;Oettle and Riess, 2002), cisplatinum (Colucci et al, 1999, Heinemann et al, 2000, adriamycin (Scheithauer et al, 1999, Neri et al, 2002, docetaxel (Jacobs, 2002), and oxaliplatin (Louvet et al, 2002) led to higher response rates and interesting results in terms of clinical benefit. However, the majority of these studies also reported to have little effect on patient median survival (range 7 -8.3 months), and were all complicated by grade III -IV heamatological and gastroenteric toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…at different doses, with or without FA. These studies reported discordant results in terms of clinical responses, time to progression and overall survival and some of them recorded a high degree of therapy related toxicity (Grem, 1996;Hidalgo et al, 1997Hidalgo et al, , 1999Michel and Moore, 1997;Berlin et al, 1998 -99;Schulz et al, 1998;Cascinu et al, 1999;Ulrich-Pur et al, 2000;Cohen et al, 2002;Heinemann, 2002;Oettle and Riess, 2002). The results of the only phase III trial comparing the weekly schedules of 5-FU/GEM with GEM alone did not show any advantage of the combination in terms of overall survival, progression-free survival, or response rate (Berlin et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

A novel biweekly pancreatic cancer treatment schedule with gemcitabine, 5-fluorouracil and folinic acid

et al. 2003

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Pancreatic adenocarcinoma is a common disease considered to be poorly responsive to antiblastic treatment. Recent clinical and preclinical results suggest that a combined treatment of gemcitabine (GEM), 5-flurouracil (5-FU) and folinic acid (FA) offers a clinical benefit in patients with advanced pancreas adenocarcinoma. The aim of this phase II clinical trial was to evaluate the antitumour activity and toxicity of a novel biweekly schedule of this combination in patients with pancreatic adenocarcinoma. A total of 42 patients received a 30 min infusion of FA (100 mg m À2 ) and 5-FU (400 mg m À2 ) (FUFA) on days 1 -3, and GEM 1000 mg m À2 on day 1 every 15 days. We observed 13 objective responses (two complete, 11 partial) and 23 stable diseases. The median time to progression was 9.75 months (95% Confidence Interval (CI), 6.88 -12.62) and the median overall survival was 13.10 months (95% CI 9.64 -16.56). There were seven cases of each grade III gastroenteric and haematological toxicity. The GEM plus FUFA combination appears to be well tolerated and very active in patients with pancreatic carcinoma.

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“…27,29,35,38,40,46,68,79 None of the relevant studies was a high-quality RCT. Rothenberg and colleagues' trial 29 was the only one exclusively to involve individuals with relapsed disease and examined the effect of gemcitabine in patients with metastatic pancreatic cancer that had progressed despite the administration of 5-FU.…”

Section: Gemcitabine As a Second Line Treatmentmentioning

confidence: 99%

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of gemcitabine for the treatment of pancreatic cancer

Ward

Morris²,

Bansback³

et al. 2001

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A phase II trial of biweekly high dose gemcitabine for patients with metastatic pancreatic adenocarcinoma

Cited by 43 publications

References 20 publications

Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway

Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway

A novel biweekly pancreatic cancer treatment schedule with gemcitabine, 5-fluorouracil and folinic acid

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of gemcitabine for the treatment of pancreatic cancer

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