Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer

Glimelius, Bengt; Hoffman, Katarina; Sjödén, Per Olow; Jacobsson, Gunilla; Sellström, H; Enander, L.-K.; Linné, Thomas; Svensson, C.

doi:10.1093/oxfordjournals.annonc.a010676

Cited by 740 publications

(472 citation statements)

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“…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). More recently, gemcitabine was shown in a randomized trial to increase median survival time to 5.7 months compared to 4.4 months in patients given bolus 5-FU (Burris et al, 1997).…”

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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“…To date, the only randomised trial for advanced biliary carcinomas, including an observational control arm, has shown an improvement of overall survival (OS) (6.5 versus 2.5 months) as well as quality of life, assessing a regimen of 5-FU plus leucovorin with or without etoposid, as compared to best supportive care (Glimelius et al, 1996).…”

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Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

et al. 2008

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This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m À2 , day 1) plus capecitabine (1000 mg m À2 b.i.d., days 1 -14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0 -15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3 -11.7; ECC: 16.8 months; 95% CI, 12.7 -20.5), and 5.2 months (95% CI, 0.6 -9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3 -4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.

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“…Unfortunately, most patients have locally advanced or metastatic pancreatic cancer and usually are poorly responsive to chemotherapy (Greenlee et al, 2001). Randomised studies have revealed a significant better overall survival (OS) with chemotherapy against best supportive care (BSC) (Weinerman and MacCormick, 1994;Glimelius et al, 1996). Although the increase in median survival was modest: 4 and 6 months for the treatment group as compared with 3 and 2.5 months for BSC, respectively, various schedules and different regimens have been evaluated with no proven benefit over single-agent 5-fluorouracil (5-FU) (Cullinan et al, 1985;Cullinan et al, 1990).…”

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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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Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer

Cited by 740 publications

References 40 publications

A phase II trial of marimastat in advanced pancreatic cancer

A phase II trial of marimastat in advanced pancreatic cancer

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

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)

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