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

Hong, Sung Pil; Park, J. Y.; Jeon, Tae Joo; Bang, Seungmin; Park, S. W.; Chung, Jae Bock; Park, M. S.; Seong, Jinsil; Lee, Woo Jung; Song, Si Young

doi:10.1038/sj.bjc.6604247

Cited by 22 publications

(10 citation statements)

References 27 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data clearly show that CPEC is biologically active because it transiently depletes CTP levels both in tumour tissue and in the jejunum, which is the critical normal tissue for chemo-radiation treatment of locally advanced pancreatic cancer (11)(12)(13)(14). We also show prolonged and tumour-selective depletion of CTP levels that would allow for an increase in the therapeutic ratio of gemcitabine and radiation.…”

Section: Discussionsupporting

confidence: 51%

“…These models are clinically relevant, because gemcitabine is used for the treatment of patients with both pancreatic and non-small cell lung cancer. Moreover, gemcitabine is used in combination with radiotherapy albeit with a small therapeutic ratio (11)(12)(13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

“…Since gemcitabine enhances the radiosensitivity of tumour cells in vitro and in vivo (3)(4)(5)(6)(7)(8)(9)(10), several phase I and II studies have investigated concurrent gemcitabine and radiotherapy. Unfortunately, acute gastrointestinal toxicity was encountered with standard doses of gemcitabine and radiotherapy, which depended on the irradiated volume (11)(12)(13)(14). Also in patients with nonsmall cell lung cancer (NSCLC) caution needs to be used, when gemcitabine and radiotherapy are applied concurrently (15).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

Kal¹

2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Cyclopentenyl cytosine (CPEC), targetting the de novo biosynthesis of cytidine triphosphate (CTP), increases the cytotoxicity of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) alone and in combination with irradiation in several human tumour cells in vitro. We investigated whether CPEC enhances the therapeutic ratio of gemcitabine and irradiation in human pancreatic BxPC-3 xenografts and in rat syngeneic L44 lung tumours. These models were selected because gemcitabine and radiation are used to treat both pancreatic and lung cancer patients and both models differ in growth capacity and in gemcitabine-induced radiosensitisation. A profound dose-dependent CTP-depletion was observed after a single injection of CPEC in both tumour tissue and in normal jejunum. In both models, CPEC alone induced a slight but significant tumour growth delay. The combination of CPEC with gemcitabine, at time intervals that showed CTP-depletion after CPEC, enhanced neither tumour growth delay nor toxicity as compared to gemcitabine alone. In addition, no beneficial effect of CPEC was observed in combination with gemcitabine and radiation. These results suggest that CPEC and gemcitabine alone as well as in combination with radiation target a similar cell population in both tumour models. In conclusion, future clinical development of CPEC as a modulator of gemcitabine combined with radiation is unlikely.

show abstract

Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

Kal¹

2009

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Chemoradiotherapy (CRT) also has been investigated widely in patients with LAPC; McGinn et al (2001) were among the first to introduce gemcitabine in CRT protocols for LAPC treatment. Subsequently, several other groups also conducted phase I and II clinical trials to improve CRT protocols for LAPC by including newer cytotoxic agents such as gemcitabine, cisplatin, or oxaliplatin as concurrent radiosensitising agents in their radiotherapy regimens (Desai et al, 2007;Haddock et al, 2007;Hong et al, 2008;Small et al, 2008). More recently, the final results from the first randomised trial comparing systemic chemotherapy alone with CRT (followed by maintenance chemotherapy) in LAPC were reported by Chauffert et al (2008): overall survival (OS), the primary study end point, was shorter in the CRT arm (8.6 months) than in the gemcitabine chemotherapy arm (13 months, P ¼ 0.03; Chauffert et al, 2008).…”

mentioning

confidence: 99%

Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer – a multi-centre randomised phase II study

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: No standard treatment for locally advanced pancreatic cancer (LAPC) is defined. PATIENTS AND METHODS: Within a multi-centre, randomised phase II trial, 95 patients with LAPC were assigned to three different chemoradiotherapy (CRT) regimens: patients received conventionally fractionated radiotherapy of 50 Gy and were randomised to concurrent 5-fluorouracil (350 mg m À2 per day on each day of radiotherapy, RT-5-FU arm), concurrent gemcitabine (300 mg m À2 ), and cisplatin (30 mg m À2 ) on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by sequential full-dose gemcitabine (1000 mg m À2 ) and cisplatin (50 mg m À2 ) every 2 weeks (RT-GC þ GC arm). Primary end point was the overall survival (OS) rate after 9 months. RESULTS: The 9-month OS rate was 58% in the RT-5-FU arm, 52% in the RT-GC arm, and 45% in the RT-GC þ GC arm. Corresponding median survival times were 9.6, 9.3, and 7.3 months (P ¼ 0.61) respectively. The intent-to-treat response rate was 19, 22, and 13% respectively. Median progression-free survival was estimated with 4.0, 5.6, and 6.0 months (P ¼ 0.21). Grade 3/4 haematological toxicities were more frequent in the two GC-containing arms, no grade 3/4 febrile neutropaenia was observed. CONCLUSION: None of the three CRT regimens tested met the investigators' definition for efficacy; the median OS was similar to those previously reported with gemcitabine alone in LAPC.

show abstract

“…Because of apprehension in regard to increasing the rate of treatment-related toxicity, most studies have adopted diminished gemcitabine doses or reduced the total dose of concurrent RT [10,11,12,13]. On the other hand, some trials have insisted that FG-CCRT is relatively safe [14]. …”

Section: Introductionmentioning

confidence: 99%

Full-Dose Gemcitabine Is a More Effective Chemotherapeutic Agent Than 5-Fluorouracil for Concurrent Chemoradiotherapy as First-Line Treatment in Locally Advanced Pancreatic Cancer

Kang

Chang

et al. 2014

Chemotherapy

View full text Add to dashboard Cite

Objectives: To compare the efficacy of full-dose gemcitabine-based concurrent chemoradiotherapy (FG-CCRT) and conventional 5-fluorouracil CCRT (5FU-CCRT) for locally advanced pancreatic cancer (LAPC). Methods: 109 LAPC cases treated with FG-CCRT (n = 89) or 5FU-CCRT (n = 20) were reviewed retrospectively. The FG-CCRT group was composed of a full-dose gemcitabine monotherapy (1,000 mg/m²) arm and a combination therapy with cisplatin (70 mg/m²) arm. The 5FU-CCRT group used a radiosensitizing dose of 5-FU (500 mg/m²) plus leucovorin (20 mg/m²). Concurrent radiotherapy was targeted at the tumor with a 5-mm margin without lymph node irradiation. Results: Objective response rate (ORR) and disease control rate (DCR) was significantly higher in the FG-CCRT group (ORR: 32.6 vs. 5%, p = 0.013; DCR: 79.8 vs. 50.0%, p = 0.006). FG-CCRT showed remarkable superiority to 5FU-CCRT for suppressing distant metastasis (18.0 vs. 45.0%, p = 0.017). Neutropenia (34.8 vs. 10%, p = 0.032) and thrombocytopenia (21.3 vs. 0.0%, p = 0.021) were more frequent in the FG-CCRT group as originally expected. When dividing the FG-CCRT group to gemcitabine monotherapy (GEM) and gemcitabine plus cisplatin, toxicities of the GEM subgroup were not different than those of the 5FU-CCRT group. Conclusion: FG-CCRT, especially full-dose gemcitabine monotherapy-based CCRT was more effective for the initial control of LAPC than 5FU-CCRT, and also relatively safe.

show abstract

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

Cited by 22 publications

References 27 publications

Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer – a multi-centre randomised phase II study

Full-Dose Gemcitabine Is a More Effective Chemotherapeutic Agent Than 5-Fluorouracil for Concurrent Chemoradiotherapy as First-Line Treatment in Locally Advanced Pancreatic Cancer

Contact Info

Product

Resources

About