Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial

Scheithauer, Werner; Schüll, Birgit; Ulrich‐Pur, Herbert; Schmid, Katharina; Raderer, Markus; Haider, Karin; Kwasny, Werner; Depisch, D.; Schneeweiß, Bruno; Lang, F.; Kornek, Gabriela

doi:10.1093/annonc/mdg029

Cited by 169 publications

(95 citation statements)

References 23 publications

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“…Nineteen studies involving 4697 patients were included (Supplementary Table 2) (Berlin et al, 2002;Colucci et al, 2002;Wang et al, 2002;Heinemann et al, 2003;Scheithauer et al, 2003;Li and Chao, 2004;Ohkawa, 2004;Rocha Lima et al, 2004;Viret et al, 2004;Cunningham et al, 2005 Cullinan 1990 Cullinan 1990 Cullinan 1990 …”

Section: Gemcitabine Vs Gemcitabine-based Combination Chemotherapymentioning

confidence: 99%

Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses

Sultana¹,

Smith

Cunningham

et al. 2008

Br J Cancer

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In advanced pancreatic cancer, level one evidence has established a significant survival advantage with chemotherapy, compared to best supportive care. The treatment-associated toxicity needs to be evaluated. This study examines the secondary outcome measures for chemotherapy in advanced pancreatic cancer using meta-analyses. A systematic review was undertaken employing Cochrane methodology, with search of databases, conference proceedings and trial registers. The secondary end points were progression-free survival (PFS)/time to progression (TTP) (summarised using the hazard ratio (HR)), response rate and toxicity (summarised using relative risk). There was no significant advantage of 5FU combinations vs 5FU alone for TTP (HR ¼ 1.02; 95% CI ¼ 0.85 -1.23) and toxicity. Progression-free survival (HR 0.78; CI 0.70 -0.88), TTP (HR ¼ 0.85; 95% CI ¼ 0.72 -0.99) and overall response rate (RR ¼ 0.56; 95% CI ¼ 0.46 -0.68) were significantly better for gemcitabine combination chemotherapy, but offset by the greater grade 3/4 toxicity thrombocytopenia (RR ¼ 1.94; 95% CI ¼ 1.32 -2.84), leucopenia (RR ¼ 1.46; 95% CI ¼ 1.15 -1.86), neutropenia (RR ¼ 1.48; 95% CI ¼ 1.07 -2.05), nausea (RR ¼ 1.77; 95% CI ¼ 1.37 -2.29), vomiting (RR ¼ 1.64; 95% CI ¼ 1.24 -2.16) and diarrhoea (RR ¼ 2.73; 95% CI ¼ 1.87 -3.98). There is no significant advantage on secondary end point analyses for administering 5FU in combination over 5FU alone. There is improved PFS/TTP and response rate, with gemcitabine-based combinations, although this comes with greater toxicity.

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Section: Gemcitabine Vs Gemcitabine-based Combination Chemotherapymentioning

confidence: 99%

Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses

Sultana¹,

Smith

Cunningham

et al. 2008

Br J Cancer

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“…The combination of gemcitabine and 5-fluoro-2 0 -deoxyuridine (an intermediate metabolite of capecitabine) has demonstrated synergistic activity in vitro (Ren et al, 1998). Several phase I trials have evaluated combinations of gemcitabine and capecitabine, and have shown that full single-agent doses can be delivered in combination (Schilsky et al, 2002;Hess et al, 2003;Scheithauer et al, 2003). This single institution phase II trial aimed to evaluate the activity and toxicity of a combination of gemcitabine and capecitabine in patients with metastatic renal cancer refractory to or unsuitable for immunotherapy.…”

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confidence: 99%

Phase II clinical trial of capecitabine and gemcitabine chemotherapy in patients with metastatic renal carcinoma

et al. 2004

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“…Recent studies on erlotinib, an epidermal growth factor receptor inhibitor, plus gemcitabine, provided the foundation for approval of such regimens for the treatment of advanced pancreatic adenocarcinoma (24) and reported a SDR of 53-59.3% (25,26). The most frequently reported treatment-related toxicities of gemcitabine, alone or in combination with other drugs, are leukopenia, thrombocytopenia and neutropenia (26,27).…”

Section: Discussionmentioning

confidence: 99%

Phase I trial of M2ES, a novel polyethylene glycosylated recombinant human endostatin, plus gemcitabine in advanced pancreatic cancer

Chen

et al. 2014

Molecular and Clinical Oncology

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Abstract. Pancreatic cancer is one of the most lethal and resistant to treatment of solid tumors. Combination therapies with various types of drugs against pancreatic cancer have been extensively investigated. Endostatin is a potent endogenous inhibitor of angiogenesis, which may be administered in combination with various chemotherapeutic agents in the treatment of several types of cancer. To the best of our knowledge, this phase I trial was the first clinical study to determine the tolerance, safety and efficacy of M 2 ES, a novel polyethylene glycosylated recombinant human endostatin, administered concurrently with full-dose gemcitabine in patients with inoperable, locally advanced or metastatic pancreatic adenocarcinoma. A total of 16 patients were treated with gemcitabine (1,000 mg̸m 2 on days 1, 8 and 15) and M 2 ES (5-45 mg̸m 2 on days 1, 8, 15 and 21) of each 28-day cycle. In 15 evaluable patients, the stable disease rate (SDR) was 40% (95% CI: 11.9-68.1%). In particular, a 75% SDR was observed in 3 out of 4 patients with a M 2 ES dose level of 7.5 mg/m 2 . The most noticeable M 2 ES-related adverse events observed during the trial were grade 2 liver function abnormalities (6.3%) and grade 1 skin rash (6.3%). No dose-limiting toxicity was observed in any patients from all the dose levels. Therefore, there was no increased toxicity associated with the addition of M 2 ES to gemcitabine and this combination was well tolerated.

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Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial

Cited by 169 publications

References 23 publications

Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses

Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses

Phase II clinical trial of capecitabine and gemcitabine chemotherapy in patients with metastatic renal carcinoma

Phase I trial of M2ES, a novel polyethylene glycosylated recombinant human endostatin, plus gemcitabine in advanced pancreatic cancer

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