Comparison of Gemcitabine Versus the Matrix Metalloproteinase Inhibitor BAY 12-9566 in Patients With Advanced or Metastatic Adenocarcinoma of the Pancreas: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group

Moore, Malcolm J.; Hamm, John; Dancey, Janet; Eisenberg, Peter D.; Dagenais, Michel; Fields, Anthony; Hagan, K.; Greenberg, Bernard R.; Colwell, Bruce; Zee, Benny; Tu, Dongsheng; Ottaway, J.; Humphrey, Rachel; Seymour, Lesley

doi:10.1200/jco.2003.02.098

Cited by 357 publications

(178 citation statements)

References 17 publications

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“…However, as summarized in Table 4, with the exception of erlotinib, the completed phase III trials have not confirmed an important clinical benefit [45][46][47][48][49][50][51].…”

Section: Gemcitabine Plus Erlotinib: Statistical Significance Versus mentioning

confidence: 99%

Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty?

2008

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Pancreatic cancer is the fourth most common cause of adult cancer death in the U.S. The high mortality rate from pancreatic cancer is a result of the high incidence of metastatic disease at the time of diagnosis, an often fulminant clinical course, and the lack of adequate systemic therapies. Unfortunately, only 5%-25% of patients present with tumors amenable to resection. The median diseasefree survival interval following resection for operable pancreatic cancer is 13.4 months for patients treated with adjuvant gemcitabine and 6.9 months for untreated patients. A much higher percentage of patients present with metastatic disease (40%-45%) or locally advanced disease (40%), and have median survival times of 3-6 months or 8 -12 months, respectively. The frustrating lack of significant clinical advancements in the treatment of metastatic pancreatic cancer remains one of medical oncology's biggest disappointments. The past decade-long frustration has resulted in regulators, investigators, and practicing oncologists gradually lowering their standards/expectations with regard to interpreting clinical trials. Two of the more important examples of this include the approval of gemcitabine plus erlotinib and the use of a progressionfree survival advantage to defend the use of gemcitabine plus oxaliplatin. Given the marginal benefit of systemic antineoplastics, a scholarly review inclusive of other palliative strategies will help oncologists optimize the care of pancreatic cancer patients. This article examines the existing evidence in support of a role for palliative therapy in metastatic pancreatic cancer, describes recent developments with newer chemotherapeutic and molecular-targeted agents, and explores future study designs. The Oncologist 2008;13:562-576

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“…However, as summarized in Table 4, with the exception of erlotinib, the completed phase III trials have not confirmed an important clinical benefit [45][46][47][48][49][50][51].…”

Section: Gemcitabine Plus Erlotinib: Statistical Significance Versus mentioning

confidence: 99%

Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty?

2008

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“…Chemotherapy as a sole modality improves survival in patients with locally advanced or metastatic disease (Palmer et al, 1994;Glimelius et al, 1996); however, even with the current regimens, median overall survival has ranged from 3.3 to 11.5 months in phase II trials and has generally been not more than 7 months in phase III trials (Burris et al, 1997;Berlin et al, 2002;Colucci et al, 2002;Maisey et al, 2002;Moore et al, 2003;Petty et al, 2003;Rocha Lima et al, 2004;Lopes and Rocha Lima, 2005;Louvet et al, 2005;Oettle et al, 2005). There is little published information on the effectiveness of chemotherapy alone in preventing local failure, but an apparent improvement in survival has been reported in two recent large phase III studies, which had a significant subset of patients with locally advanced disease Poplin et al, 2006a).…”

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confidence: 99%

Gemcitabine with a specific conformal 3D 5FU radiochemotherapy technique is safe and effective in the definitive management of locally advanced pancreatic cancer

et al. 2007

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The aim of this phase II study was to assess the feasibility and efficacy of a specific three-dimensional conformal radiotherapy technique with concurrent continuous infusion of 5-fluorouracil (CI 5FU) sandwiched between gemcitabine chemotherapy in patients with locally advanced pancreatic cancer. Patients with inoperable cancer in the pancreatic head or body without metastases were given gemcitabine at 1000 mg m À2 weekly for 3 weeks followed by a 1-week rest and a 6-week period of radiotherapy and concurrent CI 5FU (200 mg m À2 day À1 ). The defined target volume was treated to 54 Gy in 30 daily fractions of 1.8 Gy. After 4 weeks' rest, gemcitabine treatment was re-initiated for three cycles (days 1, 8, 15, q28). Forty-one patients were enrolled. At the end of radiotherapy, one patient (2.4%) had a complete response and four patients (9.6%) had a partial response; at the end of treatment, three patients (7.3%) had a complete response and two patients (4.9%) had a partial response. Median survival time was 11.7 months, median time to progression was 7.1 months, and median time to failure of local control was 11.9 months. The 1-and 2-year survival rates were 46.3 and 9.8%, respectively. Treatment-related grade 3 and 4 toxicities were reported by 16 (39.0%) and four (9.8%) patients, respectively. Sixteen out of 41 patients did not complete the planned treatment and nine due to disease progression. This approach to treatment of locally advanced pancreatic cancer is safe and promising, with good local control for a substantial proportion of patients, and merits testing in a randomised trial.

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“…Newer cytotoxic agents such as premetrexed , exatecan (Cheverton et al, 2004;O' Reilly et al, 2004), oxaliplatin (Louvet et al, 2005), irinotecan (Rocha Lima et al, 2004) and novel agents targeting matrix metalloproteinase (Bramhall et al, 2001(Bramhall et al, , 2002Moore et al, 2003), and farnesyltransferase (Van Cutsem et al, 2004) had all entered phase III testing either alone or in combination with gemcitabine -the current standard of care. Yet despite these efforts, none of these drugs have shown an OS advantage over gemcitabine monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials

et al. 2006

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Gastrin has been shown to be a growth stimulant in pancreatic cancer cells. Gastrazole is a potent and selective gastrin receptor antagonist. Two randomised blinded trials were conducted to assess the effect of gastrazole in advanced pancreatic cancer. Patients with biopsy-proven, inoperable pancreatic carcinoma were recruited. Trial A compared protracted venous infusion (PVI) gastrazole with PVI placebo, whereas trial B compared PVI gastrazole with PVI fluorouracil (5-FU). Eighteen patients were randomised in trial A. Gastrazole produced significantly better survival compared to placebo (median 7.9 months vs 4.5 months; 1-year survival: 33 vs 11%, respectively; log rank P ¼ 0.02). No difference in toxicity was seen between gastrazole and placebo, except central venous catheter and pump complications. Ninety-eight patients were randomised in trial B. No significant survival difference was detected between gastrazole and 5-FU (median: 3.6 vs 4.2 months; 1-year survival: 13.2 vs 26.2%, respectively; log rank P ¼ 0.42). Toxicity of gastrazole was mild with significantly less diarrhoea (P ¼ 0.03), stomatitis (Po0.001) and hand -foot syndrome (Po0.001) compared to 5-FU. Quality of life (QoL) assessment showed similar QoL between gastrazole and 5-FU at baseline and no significant differences occurred with treatment either between arms or within arms. Compared to placebo, patients with advanced pancreatic cancer treated with gastrazole appeared to live longer, albeit in a very small trial and will require confirmation with large-scale randomised data. However, it did not produce survival advantage over PVI 5-FU. Lack of toxicity for gastrazole may allow its combination with cytotoxic drugs.

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Comparison of Gemcitabine Versus the Matrix Metalloproteinase Inhibitor BAY 12-9566 in Patients With Advanced or Metastatic Adenocarcinoma of the Pancreas: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group

Abstract: Gemcitabine is significantly superior to BAY 12-9566 in advanced pancreatic cancer.

Cited by 357 publications

References 17 publications

Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty?

Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty?

Gemcitabine with a specific conformal 3D 5FU radiochemotherapy technique is safe and effective in the definitive management of locally advanced pancreatic cancer

Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials

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