Phase I Trial of Radiation Dose Escalation With Concurrent Weekly Full-Dose Gemcitabine in Patients With Advanced Pancreatic Cancer

McGinn, Cornelius J.; Zalupski, Mark M.; Shureiqi, Imad; Robertson, John M.; Eckhäuser, Frederic E.; Smith, David C.; Brown, Diane; Hejna, Gwen; Strawderman, Myla; Normolle, Daniel P.; Lawrence, Theodore S.

doi:10.1200/jco.2001.19.22.4202

Cited by 291 publications

(169 citation statements)

References 17 publications

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“…Although we found no consensus between administration schedules for gemcitabine with radiation, recent studies have used twice weekly or weekly administrations of gemcitabine for their main therapeutic schedules (Blackstock et al, 1999;McGinn et al, 2001;Okusaka et al, 2004;Magnino et al, 2005). According to the fact that patients with resectable pancreatic cancer developed early recurrence after surgery due to micrometastases and distant early metastases were important cause of treatment failure of chemoradiotherapy in patients with locally advanced pancreatic cancer, we used weekly gemcitabine treatments in our study (Yeo et al, 1997;Paulino and Latona, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we used a full dose of gemcitabine (1000 mg m À2 ) to maximise systemic cytotoxicity. Although most of the recent phases I and II studies were performed using a submaximal dose of gemcitabine with radiotherapy, a study by McGinn et al (2001) reported that the standard full dose of gemcitabine was acceptable. Our previous experience also showed that radiotherapy with a full dose of gemcitabine was tolerable (Chung et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Previous phases I and II studies were performed with radiotherapy doses of 42 -50.4 Gy and sometimes used boosting doses to achieve local control (Blackstock et al, 1999;McGinn et al, 2001;Brunner et al, 2003;Okusaka et al, 2004;Magnino et al, 2005). In the present study, we used radiation doses of 45 Gy with 25 fractions.…”

Section: Discussionmentioning

confidence: 99%

“…In recent decades, 5-FU has been considered the standard cytotoxic agent and radiosensitiser for use with concurrent radiotherapy. Since 1996, gemcitabine, a pyrimidine analogue and potent radiosensitiser, has been studied as a substitute for 5-FU in treatments using concurrent chemoradiotherapy (Blackstock et al, 1999;McGinn et al, 2001). Recent phases I and II studies on gemcitabine-based chemoradiotherapy were feasible and improved therapeutic response and survival (Blackstock et al, 1999;McGinn et al, 2001;Okusaka et al, 2004;Magnino et al, 2005).…”

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Weekly full-dose gemcitabine and single-dose cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

et al. 2008

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The aim of this study was to evaluate the efficacy and the toxicity of a full dose of gemcitabine and a single dose of cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Forty-one patients with locally advanced pancreatic cancer were enrolled. Patients received gemcitabine (1000 mg m À2 on days 1, 8, 15, 29, and 36) and cisplatin (70 mg m À2 on days 1 and 29) with concurrent radiotherapy (45 Gy in 25 fractions). Treatment was completed in 38 out of 41 patients (92.7%). The overall response rate was 24.4% (two complete and eight partial). Six patients (14.6%) underwent definite pancreatic resection and four had negative surgical margins. The intention of the treatment analysis showed that the median survival time and median time to tumour progression were 16.7 and 8.9 months. The 1-and 2-year survival rates were 63.3 and 27.9%, respectively. Overall survival was significantly longer in the low baseline CA19-9 group and therapeutic responders. Toxicities were tolerable and successfully managed by conservative treatments. The therapeutic scheme of a weekly full dose of gemcitabine and a single dose of cisplatin combined with external radiation is effective and might prolong the survival of patients with locally advanced pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Weekly full-dose gemcitabine and single-dose cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

et al. 2008

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“…Furthermore, since the gemcitabine group has a beneficial effect on survival rate compared with the fluorouracil group, gemcitabine is the drug of choice for progressive pancreatic cancer at present. However, in recent findings, there is a significant toxic effect of gemcitabine combined with radiation in the treatment of advanced pancreatic cancer (McGinn et al, 2001(McGinn et al, , 2002Wolff et al, 2001;Crane et al, 2002). In addition, since existing antipancreatic cancer drugs have no eradicative potency, it is necessary to find medicines that have new mechanisms of antitumour activity.…”

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confidence: 99%

Antitumour effect of polyoxomolybdates: induction of apoptotic cell death and autophagy in in vitro and in vivo models

et al. 2007

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O. The effect of PM-17 on the growth of cancer cell lines and xenografts was assessed by a cell viability test and analysis of tumour expansion rate. Morphological analysis was carried out by Hoechst staining, flow-cytometric analysis of Annexin V staining, terminal deoxynucleotidyl transferase-mediated 'nick-end' labelling staining, and electron-microscopic analysis. Activation of autophagy was detected by western blotting and fluorescence-microscopic analysis of the localisation of GFP-LC3 in transfected tumour cells. PM-17 inhibited the growth of human pancreatic cancer (AsPC-1) xenografts in a nude mice model, and induced morphological alterations in tumour cells. Correspondingly, PM-17 repressed the proliferation of AsPC-1 cells and human gastric cancer cells (MKN45) depending on the dose in vitro. We observed apoptotic patterns as the formation of apoptotic small bodies and translocation of phosphatidylserine by Hoechst staining and flow-cytometric analysis following Annexin V staining, and in parallel, autophagic conformation by the formulation of autophagosomes and localisation of GFP-LC3 by electron-and fluorescence-microscopic analysis.

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Modern Approaches to Radiation Therapy

Tsien

Lawrence

2007

The Cancer Handbook

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Recent advances in technology have led to dramatic improvements in radiation treatment planning, and delivery. These technical advances have allowed us to deliver higher radiation doses to the tumour while limiting dose to the normal surrounding tissues. Parallel advances in imaging and molecular biology have improved our ability precisely to define target volumes at risk, enhance radiation sensitivity, as well as to evaluate response to therapy. In this chapter, we will focus on the clinical improvements that have been achieved from both technological advances in radiotherapy (RT) planning and treatment delivery in combination with radiation response modifiers such as altered fractionation, chemotherapy, and molecularly targeted therapy.

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Phase I Trial of Radiation Dose Escalation With Concurrent Weekly Full-Dose Gemcitabine in Patients With Advanced Pancreatic Cancer

Cited by 291 publications

References 17 publications

Weekly full-dose gemcitabine and single-dose cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

Weekly full-dose gemcitabine and single-dose cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

Antitumour effect of polyoxomolybdates: induction of apoptotic cell death and autophagy in in vitro and in vivo models

Modern Approaches to Radiation Therapy

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