Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer

Heinemann, Volker; Quietzsch, D.; Gieseler, Frank; Gonnermann, Michael; Schönekäs, H; Rost, Andreas; Neuhaus, Horst; Haag, Caroline; Clemens, Michael; Heinrich, Bernard; Vehling-Kaiser, Ursula; Fuchs, Martin; Fleckenstein, Doris; Gesierich, Wolfgang; Uthgenannt, Dirk; Einsele, Hermann; Holstege, Axel; Hinke, Axel; Schalhorn, Andreas; Wilkowski, Ralf

doi:10.1200/jco.2005.05.1490

Cited by 623 publications

(374 citation statements)

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“…In this study, we used a single dose of cisplatin combined with gemcitabine. There is a report that median TTP and ORR were significantly improved with combined chemotherapy of gemcitabine and cisplatin in patients with locally advanced and metastatic pancreatic cancer (Colucci et al, 2002;Heinemann et al, 2006). Recent phases I and II trials of chemoradiotherapy with a combination of gemcitabine and cisplatin in locally advanced pancreatic cancer patients used a divided dose of cisplatin (Brunner et al, 2003;Wilkowski et al, 2004;Haddock et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The combination of gemcitabine and cisplatin has a synergistic effect in vitro in which gemcitabine can inhibit the DNA repair mechanism after cisplatininduced damage, and cisplatin influences gemcitabine metabolism through the inhibition of ribonucleotide reductase (Peters et al, 1995;Bergman et al, 1996). A recent phase III trial with gemcitabine (1000 mg m À2 ) and cisplatin (50 mg m À2 ) on days 1 and 15 of a 4-week cycle showed favourable median OS and median time to tumour progression (TTP) compared with gemcitabine alone in advanced pancreatic cancer (Heinemann et al, 2006). We recently reported the feasibility and clinical efficacy of cisplatin combined with weekly gemcitabine treatments for patients with metastatic pancreatic cancer (Bang et al, 2006b).…”

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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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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%

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confidence: 99%

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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“…Table 1 lists randomized phase III trials of gemcitabine combined with a second agent. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Results among the studies were similar; the addition of a chemotherapeutic agent to gemcitabine did not improve overall survival or quality of life compared with single-agent gemcitabine, with the possible exceptions of gemcitabine plus capecitabine and gemcitabine plus a platinum agent.…”

Section: Gemcitabine In Combination Trialsmentioning

confidence: 99%

Cancer of the Pancreas: Are we Making Progress? A Review of Studies in the US Oncology Research Network

2008

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Risk factors for cancer of the pancreas include age (50 years and older), male sex, race (black), smoking, a diet high in meats and fat, presence of diabetes or chronic pancreatitis, exposure to chemicals in the workplace, and a family history.Most cases of pancreatic cancer are advanced at the time of diagnosis. Usually by the time symptoms are present, pancreatic tumors are typically unresectable, and there are no curative options. Only about 10% to 15% of patients who present with pancreatic cancer are considered eligible for resection. The tumor must be localized and not invade adjacent vascular structures such as the portal vein, celiac axis, superior mesenteric artery or vein, or the hepatic artery. Determination of resectability typically involves a computed tomography (CT) scan of the abdomen and pelvis as well as endoscopic retrograde cholangiopancreatography (ERCP) IntroductionPancreatic cancer is the fourth leading cause of cancer deaths in the United States. In 2008, an estimated 37,680 people will be diagnosed with pancreatic cancer in the United States, and 34,290 will die of the disease. 1 Only 23% of patients with cancer of the exocrine pancreas will survive for 1 year, while about 4% will survive for 5 years. Cancer of the Pancreas: Are We Making Progress? A Review of Studies in the US Oncology Research Network

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“…Clinical trials combining gemcitabine with cytotoxic agents have been investigated. In advanced or metastatic pancreatic cancer, combinations of gemcitabine plus 5-fluorouracil (5-FU) [4], cisplatin [5], oxaliplatin [6] and irinotecan [7] have not shown significant benefit in overall survival compared to single-agent gemcitabine. Capecitabine, an orally administered fluoropyrimidine carbamate which converts to active 5-FU in the tumour site demonstrates efficacy in untreated advanced colorectal carcinoma [8] and the combination of gemcitabine and capecitabine in advanced pancreatic cancer improves overall survival, clinical benefit response and quality of life at a statistically significant level compared with standard gemcitabine treatment [9,10].…”

Section: Introductionmentioning

confidence: 99%

EGFR and HER2 inhibition in pancreatic cancer

et al. 2012

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Summary The aim of this study was to investigate the effect of lapatinib, a selective inhibitor of EGFR/HER2 tyrosine kinases, on pancreatic cancer cell lines both alone and in combination with chemotherapy. Two cell lines, BxPc-3 and HPAC, displayed the greatest sensitivity to lapatinib (IC 50 < 2 μM). Lapatinib also demonstrated some activity in three KRas mutated pancreatic cancer cell lines which displayed resistance to erlotinib. Drug effect/combination index (CI) isobologram analysis was used to study the interactions of lapatinib with gemcitabine, cisplatin and 5'deoxy-5'fluorouridine. Concentration-dependent anti-proliferative effects of lapatinib in combination with chemotherapy were observed. To evaluate the potential effect of lapatinib in pancreatic cancer tumours, and to identify a subset of patient most likely to benefit from lapatinib, expression of EGFR and HER2 were investigated in 72 pancreatic cancer tumour specimens by immunohistochemistry. HER2 membrane expression was observed in only 1 % of cases, whereas 44 % of pancreatic tumours expressed EGFR. Based on our in vitro results, lapatinib may provide clinical benefit in EGFR positive pancreatic ductal adenocarcinoma.

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Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer

Cited by 623 publications

References 20 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

Cancer of the Pancreas: Are we Making Progress? A Review of Studies in the US Oncology Research Network

EGFR and HER2 inhibition in pancreatic cancer

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