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A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.

Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA - Br. J. Cancer (2002)

Bottom Line: There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms.The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity.The combination of marimastat with gemcitabine was well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK. S.R.Bramhall@bham.ac.uk

ABSTRACT
Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m(-2)) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified.

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Related in: MedlinePlus

Primary mortality analysis (intention-to-treat).
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fig1: Primary mortality analysis (intention-to-treat).

Mentions: Final analysis of the study was performed when 90% mortality had occurred in the GM treatment group (August 1999). Differences between individual treatment groups were determined using the log-rank test. Analysis revealed no difference in overall survival between the two treatment arms (P=0.95, hazard ratio (HR) 0.99, 95% confidence intervals (CI) 0.76–1.30). There was no difference in median survival, GM (165.5 days) compared to GP (164 days) (Figure 1Figure 1


A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.

Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA - Br. J. Cancer (2002)

Primary mortality analysis (intention-to-treat).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376102&req=5

fig1: Primary mortality analysis (intention-to-treat).
Mentions: Final analysis of the study was performed when 90% mortality had occurred in the GM treatment group (August 1999). Differences between individual treatment groups were determined using the log-rank test. Analysis revealed no difference in overall survival between the two treatment arms (P=0.95, hazard ratio (HR) 0.99, 95% confidence intervals (CI) 0.76–1.30). There was no difference in median survival, GM (165.5 days) compared to GP (164 days) (Figure 1Figure 1

Bottom Line: There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms.The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity.The combination of marimastat with gemcitabine was well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK. S.R.Bramhall@bham.ac.uk

ABSTRACT
Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m(-2)) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified.

Show MeSH
Related in: MedlinePlus