Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2002 Jul 15;87(2):161-7.
doi: 10.1038/sj.bjc.6600446.

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

S R Bramhall  1 , J Schulz, J Nemunaitis, P D Brown, M Baillet, J A C Buckels
Affiliations
Clinical Trial

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

S R Bramhall et al. Br J Cancer. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Primary mortality analysis (intention-to-treat).
Figure 2
Figure 2
Time to treatment failure.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. BaileyAJParmarMKStephensRJ1998Patient-reported short-term and long-term physical and psychologic symptoms: results of the continuous hyperfractionated accelerated (correction of acclerated) radiotherapy (CHART) randomized trial in non-small-cell lung cancer. CHART Steering Committee J Clin Oncol 1630823093 - PubMed
    1. BramhallSRAllumWHJonesAGAllwoodACumminsCNeoptolemosJP1995Incidence, treatment and survival in 13,560 patients with pancreatic cancer: An epidemiological study in the West Midlands Br J Surg 82111115 - PubMed
    1. BramhallSRHallisseyMTWhitingJScholefieldJTierneyGStuartRCHawkinsREMcCullochPMaughanTBrownPDBailletMFieldingJWL2001aMarimastat as maintenance therapy for patients with advanced gastric and gastro-oesophageal cancer: A randomized trial Br J Cancer(in press)
    1. BramhallSRNeoptolemosJP1997Adjuvant chemotherapy in pancreatic cancer Int J Pancreatol 215963 - PubMed
    1. BramhallSRNeoptolemosJPStampGWLemoineNR1997Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma J Pathol 182347355 - PubMed

MeSH terms