Phase III Study of Gemcitabine in Combination With Fluorouracil Versus Gemcitabine Alone in Patients With Advanced Pancreatic Carcinoma: Eastern Cooperative Oncology Group Trial E2297

Berlin, Jordan; Catalano, Paul J.; Thomas, James P.; Kugler, John W.; Haller, Daniel G.; Benson, Al B.

doi:10.1200/jco.2002.11.149

Cited by 658 publications

(392 citation statements)

References 15 publications

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“…Berlin et al in a randomised trial of 327 patients used GEM alone weekly for 3 weeks out of every 4 weeks or GEM followed by 5-FU weekly on the same schedule (Berlin et al, 2002). The combination arm did not improve the median OS (6.7 vs 5.4 months) compared with GEM alone.…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC)

et al. 2005

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This study was performed to determine the activity of adding continuous infusion (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced pancreatic cancer (APC). In all, 94 chemo-naïve patients with APC were randomised to receive GEM alone (arm A: 1000 mg m À2 per week for 7 weeks followed by a 2 week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in combination with CI 5-FU (arm B: CI 5-FU 200 mg m À2 day À1 for 6 weeks followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall response rate (RR) was the primary end point and criteria for decision were planned according to the Simon's optimal two-stage design. The overall RR was 8% (arm A) and 11% (arm B) (95% confidence interval: 0.5 -16% and 2 -22%), respectively, and stable disease was 29 and 28%. The median duration of RR was 34 weeks (range 25 -101 weeks) for GEM and 26 weeks (range 16 -46 weeks) for the combination. The median progression-free survival (PFS) was 14 weeks (range 2 -65 weeks) and 18 weeks (range 4 -51 weeks), respectively. The median overall survival (OS) was 31 weeks (range 1 -101 weeks) and 30 weeks (1 -101 weeks). Toxicity was mild in both arms. This study does not show promising activity in terms of RR, PFS and OS for the double combination arm in APC.

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Section: Discussionmentioning

confidence: 99%

Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC)

et al. 2005

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“…30 However, the majority of these therapies used cytotoxic drugs, such as docetaxel, 5FU, cisplatin, and irinotecan. [31][32][33][34][35] Although these cytotoxic drugs exert antitumor effects by different mechanisms, the applicable dose of each drug is limited due to cumulative systemic toxicity. In such clinical trials, combination therapy may result in more adverse effects despite the expected additive antitumor effects.…”

Section: Discussionmentioning

confidence: 99%

Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival

et al. 2005

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NK4 or adenovirus vector expressing NK4 (Ad-NK4) can act bifunctionally as a hepatocyte growth factor antagonist and angiogenesis inhibitor and has potential value in cancer therapy. The aim of this study was to evaluate the therapeutic efficacy of Ad-NK4 in combination with gemcitabine (GEM) against pancreatic cancer. In vitro study showed a strong antiproliferative effect of GEM and a potent anti-invasive effect of Ad-NK4 against pancreatic cancer cells. In in vivo experiments, SUIT-2 human pancreatic cancer cells were implanted into the pancreas of nude mice. Mice were treated with Ad-NK4 by injection into the peritumoral region of the pancreas on day 5 after implantation followed by weekly i.p. injections of GEM. On day 28 after implantation, pancreatic tumor volume was significantly smaller than that in mice treated with Ad-LacZ, Ad-NK4 alone, or GEM alone. Furthermore, combination therapy completely suppressed peritoneal dissemination and liver metastases, leading to significantly increased survival. Histologic and immunohistochemical assays of primary tumors indicated that combination therapy prohibited both cell proliferation and angiogenesis, resulting in high levels of apoptosis. These results suggest that peritumoral injection of Ad-NK4 plus GEM is a potent combination therapy for pancreatic cancer.

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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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Phase III Study of Gemcitabine in Combination With Fluorouracil Versus Gemcitabine Alone in Patients With Advanced Pancreatic Carcinoma: Eastern Cooperative Oncology Group Trial E2297

Cited by 658 publications

References 15 publications

Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC)

Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC)

Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival

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

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