A phase I/II multicentric trial of gemcitabine and epirubicin in patients with advanced pancreatic carcinoma

Eickhoff, Axel; Martin, W.-R.; Hartmann, Dirk; Eickhoff, Jens; Möhler, Markus; Galle, PR; Riemann, Jürgen F.; Jakobs, Ralf

doi:10.1038/sj.bjc.6603174

Cited by 10 publications

(9 citation statements)

References 8 publications

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“…However, grade III/IV toxicity was relatively high with 51% of the patients developing neutropenia and 18% developing thrombocytopenia. Eickhoff et al [105] tested a similar regimen, but with a dose escalation where GEM 800 mg/m 2 was administered on days 1 and 8 and EPI 35 mg/m 2 was injected before the infusion of GEM on day 8. The dose escalation ended with GEM 1000 mg/m 2 and EPI 90 mg/m 2 .…”

Section: Anthracyclines As Effective Anticancer Drugsmentioning

confidence: 98%

Anthracyclines as effective anticancer drugs

Nadas¹,

Sun

2006

Expert Opinion on Drug Discovery

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Anthracyclines have received significant attention due to their effectiveness and extensive use as anticancer agents. At present, the clinical use of these drugs is offset by drug resistance in tumours and cardiotoxicity. Therefore, a relentless search for the 'better anthracycline' has been ongoing since the inception of these drugs > 30 years ago. This review focuses on the most recent pharmacology and medicinal chemistry developments on the design and use of anthracyclines. Based on their crystal structures as well as molecular modelling, a more detailed mechanism of topoisomerase poisoning by these new anthracyclines has emerged. Chemical modifications of anthracyclines have been found to possibly change the target selectivity among various topoisomerases and, thus, vary their anticancer activity. Additionally, recent sugar modifications of anthracyclines have also been found to overcome P-glycoprotein-mediated drug resistance in cancer therapy. The continued improvement of anthracycline clinical applications so far and the clinical trials of the 'third generation' of anthracyclines (such as sabarubicin) are also discussed. To finally find the 'better' anthracycline, further areas of research still need to be explored such as: the elucidation of the topoisomerase and P-glycoprotein crystal structures, molecular modelling based on crystal structure in order to design the next generation of better anthracycline drugs, the continued modifications of the anthracycline sugar moieties, and the further improvement of anthracycline drug delivery methods.

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Section: Anthracyclines As Effective Anticancer Drugsmentioning

confidence: 98%

Anthracyclines as effective anticancer drugs

Nadas¹,

Sun

2006

Expert Opinion on Drug Discovery

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“…Anthracyclines such as doxorubicin and epirubicin, are the chemotherapeutic agents associated with the highest level of oxidative stress [163], and the significance of these drugs in PDA have been the basis of multiple clinical trials. However, in a phase II trial using liposomal doxorubicin in PDA patients with unresectable tumors, the data with regard to clinical benefit was inconclusive [164], whereas co-administration of epirubicin and gemcitabine to PDA patients produced clinical benefit response [165]. …”

Section: Targeting Ros In Pda Development and Progressionmentioning

confidence: 99%

Targeting reactive oxygen species in development and progression of pancreatic cancer

Durand

Störz

2016

Expert Review of Anticancer Therapy

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Introduction Pancreatic ductal adenocarcinoma (PDA) is characterized by expression of oncogenic KRas which drives all aspects of tumorigenesis. Oncogenic KRas induces the formation of reactive oxygen species (ROS) which have been implicated in initiation and progression of PDA. To facilitate tumor promoting levels and to avoid oncogene-induced senescence or cytotoxicity, ROS homeostasis in PDA cells is balanced by additional up-regulation of antioxidant systems. Areas Covered We examine the sources of ROS in PDA, the mechanisms by which ROS homeostasis is maintained, and the biological consequences of ROS in PDA. Additionally, we discuss the potential mechanisms for targeting ROS homoeostasis as a point of therapeutic intervention. An extensive review of the relevant literature as it relates to the topic was conducted using PubMed. Expert Commentary Even though oncogenic mutations in the KRAS gene have been detected in over 95% of human pancreatic adenocarcinoma, targeting its gene product, KRas, has been difficult. The dependency of PDA cells on balancing ROS homeostasis could be an angle for new prevention or treatment strategies. These include use of antioxidants to prevent formation or progression of precancerous lesions, or methods to increase ROS in tumor cells to toxic levels.

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“…Combination of gemcitabine and epirubicin, in various doses and schedules, has been tested in patients with breast, pancreatic, ovarian, and urothelial cancers. Promising effects and acceptable toxicity were found [13][14][15][16]. The myelosuppression associated with gemcitabine is mild to moderate and there was no other overlapping toxicity with epirubicin.…”

Section: Introductionmentioning

confidence: 99%

Gemcitabine plus conventional-dose epirubicin versus gemcitabine plus cisplatin as first-line chemotherapy for stage IIIB/IV non-small cell lung carcinoma—A randomized phase II trial

Hsu¹,

Kuo²,

Hu³

et al. 2008

Lung Cancer

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A phase I/II multicentric trial of gemcitabine and epirubicin in patients with advanced pancreatic carcinoma

Cited by 10 publications

References 8 publications

Anthracyclines as effective anticancer drugs

Anthracyclines as effective anticancer drugs

Targeting reactive oxygen species in development and progression of pancreatic cancer

Gemcitabine plus conventional-dose epirubicin versus gemcitabine plus cisplatin as first-line chemotherapy for stage IIIB/IV non-small cell lung carcinoma—A randomized phase II trial

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