Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomised, multicentre trial.

Mallinson, C. N.; Rake, M. O.; Cocking, J. B.; Fox, Christopher; Cwynarski, M T; Diffey, Brian; Jackson, G A; Hanley, James A.; Wass, Val

doi:10.1136/bmj.281.6255.1589

Cited by 229 publications

(83 citation statements)

References 11 publications

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“…Frey et al found no survival benefit using a combination of 5-FU and carmustine (Frey et al, 1980). Mallison et al, however, demonstrated a median survival of 11 months using a combination of 5-FU, cyclophosphamide, methotrexate, vincristine and mitomycin C compared with 2.2 months for the untreated control group (Mallinson et al, 1980). Studies using 5-FU, doxorubicin and mitomycin C (FAM) and a combination of 5-FU, folinic acid and etoposide have similarly shown improved survival together with a better quality of life (Smith et al, 1980;Palmer et al, 1994;Glimelius et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of marimastat in advanced pancreatic cancer

et al. 2001

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Summary Pancreatic cancer has a poor response to conventional chemotherapy and radiotherapy. Inhibition of matrix metalloproteinase activity involved in tumour invasion and metastases is a novel biological approach for cancer treatment. This multicentre phase II clinical trial assessed marimastat, an oral matrix metalloproteinase inhibitor, in patients with advanced pancreatic cancer. A total of 113 patients received marimastat for 28 days at 100 mg b.d. (n = 9), 25 mg o.d. (n = 90) or 10 mg b.d. (n = 14). Patients with a response to treatment could continue marimastat beyond 28 days. Of 113 patients, 90 (80%) completed the 28-day study and 83 (73%) continued treatment. The principal side effect was arthralgia in 14 (12%) patients at 28 days and 33 (29%) patients over the whole study. There were 31 patients (27%) who required dose modification. Of 76 patients with evaluable CA19-9 levels, 23 (30%) showed no increase or fall in CA19-9. Of 83 patients with radiologically assessable disease, 41 (49%) had stable disease. The median survival was 245 days for those with a stable or falling CA19-9 level 128 days in those with rising CA19-9. The overall survival was 3.8 months. 1865-1870© 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2001.2168, available online at http://www.idealibrary.com on http://www.bjcancer.com daily dose (Drummond et al, 1995). The aim of this study was to evaluate the effect and define the tolerability of marimastat in patients with advanced pancreatic cancer. MATERIALS AND METHODS Study designThis was a multicentre open phase II pilot clinical trial to assess the effect of 28 days' administration of oral marimastat (British Biotech Pharmaceuticals Ltd, Oxford, UK) in patients with advanced pancreatic cancer with a facility to continue treatment in those patients with a clinical, serological or radiological 'response' to treatment. Marimastat was administered at a dose of 100 mg b.d., 25 mg o.d. or 10 mg b.d. with the option to reduce the dose in the event of toxicity. Patients were recruited from five centres throughout the UK between August 1995 and December 1997. Ethical committee approval was obtained from the research ethics committee at each investigating centre prior to study commencement. Study objectivesThe aims of this study were:1. To evaluate the effect of 28 days' treatment with oral marimastat on tumour size measured by computerize tomography (CT), disease progression was assessed by the level of cancer antigen CA19-9 and pain, mobility and analgesic use scores 2. To define the tolerability of marimastat 3. To assess the tumour response, safety and tolerability in patients treated beyond 28 days. Patient selectionPatients with radiologically and/or histologically/cytologically proven advanced pancreatic cancer were considered for study entry. Inclusion criteria were: (1) patients over 18 years of age; (2) Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; (3) estimated survival of at least 3 months and the ability to take food by mouth. Exclusion criteria inc...

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Section: Discussionmentioning

confidence: 99%

A phase II trial of marimastat in advanced pancreatic cancer

et al. 2001

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“…Nevertheless, previous studies have shown that palliative chemotherapy does improve overall survival compared with no treatment without impairing quality of life (Leonard et al, 1992;Mallinson et al, 1980;Palmer et al, 1994). Consequently, attempts to devise new chemotherapy regimens with the aim of improving response rates and overall survival are justified.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer

Evans

Lofts²,

Mansi³

et al. 1996

Br J Cancer

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Summary Carcinomas of the exocrine pancreas respond poorly to most chemotherapy regimens. Recently continuous infusional 5-fluorouracil (200 mg m2day') with 3 weekly cisplatin (60 mg m ) and epirubicin (50 mg m-2) (the ECF regimen) has proven to be an active regimen in gastric and breast cancer and consequently worthy of further study in pancreatic cancer. Thirty-five patients were treated with the ECF regimen as above, of whom 29 were evaluable for response and 32 were evaluable for toxicity.

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“…Several studies have reported encouraging results with single chemotherapy agents or combination treatments (Mallinson et al, 1980;Casper et al, 1994;Palmer et al, 1994;Carmichael et al, 1995;Burris et al, 1997) and gemcitabine has been compared to 5-fluorouracil (5-FU) in a phase III study in patients with advanced pancreatic cancer (Burris et al, 1997). The results of this study suggested that patients receiving gemcitabine had both an improved survival and patient benefit compared to those patients receiving 5-FU and these data and data from several other studies have led to the widespread acceptance of gemcitabine as first-line therapy in patients with advanced pancreatic cancer Carmichael et al, 1995;Rothenberg et al, 1996;Burris et al, 1997;Storniolo et al, 1999).…”

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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

et al. 2002

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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 72 ) 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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Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomised, multicentre trial.

Cited by 229 publications

References 11 publications

A phase II trial of marimastat in advanced pancreatic cancer

A phase II trial of marimastat in advanced pancreatic cancer

A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer

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

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