Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas

Pipas, J. Marc; Mitchell, Sandra E.; Barth, Richard J.; Vera-Gimón, R.; Rathmann, Joerg; Meyer, Louise P.; Wagman, Richard S; Lewis, Lionel D.; McDonnell, Carol; Colacchio, Thomas A.; Perez, Raymond P.

doi:10.1016/s0360-3016(01)01580-2

Cited by 82 publications

(36 citation statements)

References 12 publications

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“…Several experimental studies have shown that more than one mechanism leads to the potentiation of radiation-induced cell killing by gemcitabine Shewach and Lawrence, 1996;van Putten et al, 2001). In clinics, various phase I studies for radiotherapy with gemcitabine have been conducted (McGinn et al, 2001;Pipas et al, 2001;Wolff et al, 2001;Ikeda et al, 2002;Poggi et al, 2002), Figure 1 Progression-free survival and overall survival curves of patients with locally advanced pancreatic cancer receiving radiotherapy with gemcitabine. ( (12) 10 (24) 14 (33) Nausea 11 (26) 11 (26) 9 (21) …”

Section: Discussionmentioning

confidence: 99%

Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer

Okusaka¹,

Ito

Ueno³

et al. 2004

Br J Cancer

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Gemcitabine has been reported to be a potent radiosensitiser in human pancreatic cell lines. This study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. In all, 42 patients with pancreatic cancer that was unresectable but confined to the pancreatic region were treated with external-beam radiation (50.4 Gy in 28 fractions over 5.5 weeks) and weekly gemcitabine (250 mg m À2 , 30-min infusion). Maintenance gemcitabine (1000 mg m À2 weekly Â 3 every 4 weeks) was initiated 1 month after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. Of the 42 patients, 38 (90%) completed the scheduled course of chemoradiotherapy. The major toxicity was leucopenia and anorexia. There was one death attributed to duodenal bleeding and sepsis. The median survival time was 9.5 months and the 1-year survival rate was 28%. The median progression-free survival time was 4.4 months. In 35 patients with documented disease progression at the time of analysis, 34 (97%) showed distant metastasis as the cause of the initial disease progression. The chemoradiotherapy used in this study has a moderate activity against locally advanced pancreatic cancer and an acceptable toxicity profile. Future investigations for treatment with more systemic effects are warranted.

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Section: Discussionmentioning

confidence: 99%

Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer

Okusaka¹,

Ito

Ueno³

et al. 2004

Br J Cancer

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“…However, the diagnosis of PDAC often is established at an advanced stage, precluding patients from undergoing tumor resection. Despite recent therapeutic advances (3), these statistics have remained dismal because of the tumor's propensity to metastasize when small and undetectable, the advanced stage at which many patients first develop symptoms, and the intrinsic resistance of pancreatic cancer cells to cytotoxic agents and/or radiotherapy (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor-Trap Suppresses Tumorigenicity of Multiple Pancreatic Cancer Cell Lines

Fukasawa

Korc

2004

Clinical Cancer Research

109

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Purpose: Vascular endothelial growth factor A (VEGF-A) is a potent angiogenic agent that binds to two high affinity VEGF receptors (VEGFRs), a process facilitated by the low affinity neuropilin receptors. Although VEGF-A is overexpressed in pancreatic ductal adenocarcinoma, it is not known whether the in vivo growth of multiple pancreatic cancer cells can be efficiently blocked by VEGF-A sequestration.Experimental Design: Four human pancreatic cancer cell lines were grown s.c. in athymic nude mice. One cell line also was used to generate an orthotopic model of metastatic pancreatic cancer. The consequences of VEGF-A sequestration on tumor growth and metastasis were examined by injecting the mice with a soluble VEGFR chimer (VEGFTrap) that binds VEGF-A with high affinity.Results: VEGF-Trap, initiated 2 days after tumor cell inoculation, suppressed the s.c. growth of four pancreatic cancer cell lines and markedly decreased tumor microvessel density. Analysis of RNA from tumors generated with T3M4 cells revealed that VEGF-Trap decreased the expression of VEGFR-1 and neuropilin-1 and -2. VEGF-Trap, initiated 3 weeks after tumor implantation, also attenuated intrapancreatic tumor growth and metastasis in an orthotopic model using PANC-1 cells.Conclusions: VEGF-Trap is a potent suppressor of pancreatic tumor growth and metastasis and also may act to attenuate neuropilin-1 and -2 and VEGFR-1 expression. Therefore, VEGF-Trap may represent an exceedingly useful therapeutic modality for pancreatic ductal adenocarcinoma.

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“…Even at the low doses, grade 3-4 toxicity was frequent. In a phase I study (12), the maximum twice weekly tolerable dose was 50 mg/m 2 , and the authors observed one gastrointestinal bleeding one month after the therapy. Blackstock et al (13) reported that neutropenia and thrombocytopenia were not uncommon, with grade 3 neutropenia in 50%, grade 3 thrombocytopenia in 50% and grade 3 nausea/vomiting in 16% with 60 mg/m 2 biweekly GEM.…”

Section: Discussionmentioning

confidence: 99%

“…However, both hematological and non-hematological toxicities are the major concern for GEM-based treatments. In several phase I and phase II trials, concurrent GEM has been administered in different doses; however, the optimal radiosensitization dose is still not clear (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Concomitant chemoradiotherapy with low-dose weekly gemcitabine for nonmetastatic unresectable pancreatic cancer

Atasoy

Dane²,

Kefeli³

et al. 2011

Turk J Gastroenterol

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Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas

Cited by 82 publications

References 12 publications

Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer

Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer

Vascular Endothelial Growth Factor-Trap Suppresses Tumorigenicity of Multiple Pancreatic Cancer Cell Lines

Concomitant chemoradiotherapy with low-dose weekly gemcitabine for nonmetastatic unresectable pancreatic cancer

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