ISSN:0012-2823    

DOI:10.1159/000201492

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The prognosis for patients with pancreatic cancer remains extremely poor. A minority are surgically resectable, but the remainder suffer problems from locally invasive disease and also metastatic spread. Median survival in these patients approximates 4 months, with limited systemic options. Many chemotherapy drugs have been evaluated in pancreatic cancer and the results have been disappointing. Of the newer agents, gemcitabine shows the greatest promise in this tumour type. Gemcitabine is a novel pyrimidine antagonist with activity in a number of tumour types. Gemcitabine has been evaluated in 3 phase II studies revealing anti-tumour activity, albeit to a modest degree of around 10%. Many objective tumour reductions have been seen, and more importantly improved symptom control is reported by many investigators. In view of these findings a randomized phase III study was performed in the United States comparing gemcitabine with weekly 5-fluorouracil chemotherapy. Patients receiving gemcitabine achieved a higher response rate, improved symptom control and prolonged survival. These results were statistically significant. Despite the statistically significant improvement in objective response rate and survival in these patients, the outcome of systemic treatment in these patients remains extremely poor. These studies raise the question about the appropriate end-points for systemic chemotherapy trials in pancreatic cancer. Despite low objective response rates and survival improvement of approximately 6 weeks, these patients did achieve symptom control and improvements in quality of life (clinical benefit response). Gemcitabine is the first agent to be evaluated in this way and has been shown to be a benefit for approximately a quarter of the patients treated. Single agent gemcitabine could represent the standard on which to develop and evaluate new approaches. We need to improve on these results and one way forward is to look to gemcitabine containing combination chemotherapy regimens. The relative lack of toxicity associated with this drug lends itself to this approach.

ISSN:0012-2823    

DOI:10.1159/000201493

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

A number of new cytotoxic agents are currently being assessed for the treatment of gastro-intestinal cancers. Colorectal cancer has been successfully treated with several direct thymidylate synthase inhibitors, oral 5-fluorouracil analogues, irinotecan, and oxaliplatin, alone and in combination regimens. Upper gastro-intestinal malignancies are also proving responsive to combinations including irinotecan and the taxanes. Pancreatic cancer, while remaining relatively chemoresistant, is proving treatable with the new direct thymidylate synthase inhibitors, docetaxel, and gemcitabine, improvements in quality of life being an important outcome. New strategies of treatment delivery are also proving beneficial. Neo-adjuvant chemotherapy is well tolerated for the treatment of gastric cancer and results in tumour downstaging. Randomized trials will show wheter this translates into a survival advantage. Combination chemoradiation for oesophageal, pancreatic, and rectal cancers also appears to be an effective strategy. Biological therapies including hormonal manipulation, immunotherapy, angiogenesis inhibition, and gene-directed therapies are the subjects of intensive research at present, with many approaches being applied in early clinical trials. These have demonstrated the tolerability of many of these treatments with evidence for activity in some cases.

ISSN:0012-2823    

DOI:10.1159/000201494

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Background/Aims: The matrix metalloproteinases are a family of proteolytic enzymes which normally have an important physiological role in tissue remodelling and wound healing, but more recently have been implicated in the proteolytic events which occur during tumour invasion. Methods: The expanding family of matrix metalloproteinases and the specific tissue inhibitors of the matrix metalloproteinases are reviewed including their classification, structure, function, regulation of activity, and tissue expression with particular reference to pancreatic cancer. The effect of synthetic matrix metalloproteinases inhibitors in preclinical studies is reviewed together with the results of ongoing clinical trials in pancreatic cancer. Results: Pancreatic cancer is associated with the overexpression of several matrix metalloproteinases with a reduced expression of their specific inhibitors. Orally bioavailable matrix metalloproteinase inhibitors have successfully completed phase I/II clinical trials with promising results. Multicentre randomised controlled phase IIb/III clinical trials aren currently under way in pancreatic cancer. Conclusions: Matrix metalloproteinase inhibition may represent a novel approach to the management of pancreatic cancer not only in advanced disease, but in the adjuvant treatment setting following tumour resection either alone or in combination with existing chemotherapeutic agents.

ISSN:0012-2823    

DOI:10.1159/000201495

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Background/Aims: The dismal course of pancreatic adenocarcinoma patients after resection is determined by the biology of the disease preventing R-0 resections. In the spontaneous course after resection, patients frequently develop either local recurrences, liver metastases and/or peritoneal metastases. Postoperative radiochemotherapy may extend survival and reduce local recurrences without influence on hepatic progression. We performed adjuvant celiac artery infusion in pancreatic cancer, to find out whether this treatment prolongs survival and changes the biology of the disease after resection, especially by reducing liver metastasis. Methods: 20 patients received cyclic celiac artery infusions (CAI) after resection of their pancreatic cancer (18 ductal, 2 cystadenocarcinoma). The treatment consisted of 6 cycles intraarterial infusion using Seldinger’s technique with mitoxantrone (Novantron®, Wyeth-Le-derle, Germany) 10mg/m2 d1, 5-fluorouracil + folinic acid (Fluroblastin®, Farmitalia, Germany + Leucovorin®, Wyeth-Lederle) 600 mg/m2 + 170 mg/ m2 d2-4, and cis-platinum (Cisplatin®, Bristol, München, Germany) 60 mg/ m2 d5. The patients were monitored for toxicity, development of disease progression and survival. Results: The median survival time was 21 months, and only 15% of the patients developed liver metastases. The median survival time of the CAI-treated patient group compared favorably to the median survival of 9.3 months in a matched historical control group. Conclusion: Adjuvant celiac artery infusion seemed to prolong median survival and the occurrence of liver metastases appeared to be delayed or r

ISSN:0012-2823    

DOI:10.1159/000201496

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Whipple’s resection for pancreatic cancer is an inadequate procedure and should be regarded as a lumpectomy. Adjuvant treatment should be directed towards local regional and liver recurrences. In the USA, adjuvant treatment after curative Whipple resection is standard procedure, based upon results of the GITSG study in which postoperative radiotherapy and 5-FU treatment resulted in significantly better survival in 23 patients. Preliminary results of our study in Rotterdam, however, do not seem to confirm these data. In this study, 218 patients were randomly assigned to surgery only or for 40-Gy radiotherapy and 4 weeks 5-FU treatment. Another option is neoadjuvant treatment which has theoretic advantages. A number of nonrandomized studies seem to indicate that radiotherapy and 5-FU treatment may have benefit in pancreatic cancer in a neoadjuvant treatment form. It is not clear which direction to take. Randomized studies are necessary to study the effect of neoadjuvant treatment with radiotherapy and 5-FU or with regional perfusion of the pancreatic are

ISSN:0012-2823    

DOI:10.1159/000201497

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Radical resection of ductal adenocarcinoma of the pancreas affords the only realistic chance of cure. Despite some reports, in particular from Japan, suggesting an improvement in the long-term prognosis, this is true only in subgroups of selected patients. In actual fact, the overall long-term survival of resected patients is still below 10%. How meaningful is a more extended resection? The lack of randomized prospective trials involving a sufficient number of cases does not enable us to make any final conclusions. The only controlled data, recently reported by an Italian multicenter study, suggested that extended lymphadenectomy improved prognosis not in the whole population of resected patients, but only in a subgroup of patients with lymph node involvement. No definitive judgments can be made without further prospective controlled clinical trials involving a greater number of patients. The suspicion arises that surgery alone, even when extensive, may not be the best treatment for pancreatic ductal cancer.

ISSN:0012-2823    

DOI:10.1159/000201498

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Background: Although pain is the most feared part of the terminal life of many patients with cancer, the intensity and the quality of the pain is all too often only scantly described. Method: The quality and quantity of pain were prospectively registered by five variables, including a visual analogue scale (VAS), in 46 consecutive patients with exocrine pancreatic cancer. Results: Twenty-seven percent of the patients were completely pain free and 24 (53%) patients reported little or no pain at the time of diagnosis. Only 5 (11%) patients had severe pain. Patients with tumors in the head of the pancreas had less pain than patients with cancer in the body or tail of the pancreas, which could not be explained by stage or size of the tumor. With time there were less and less patients with little or no pain (VAS 0-2), but after 8 and 10 weeks about one third of the patients were still without any pain (VAS ≤ 0). With time there was also a tendency to treat patients more frequently with morphine in spite of a low pain score. Preoperative pain simply measured with VAS is an addition to prognostic information. Conclusion: Pain in pancreatic cancer is not as common as usually stated at the time of diagnosis, but is related to the site of the tumor. Eventually more patients are treated with opioid drugs. Evaluation of the pain pattern is an addition to prognostic informatio

ISSN:0012-2823    

DOI:10.1159/000201499

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Our understanding of the molecular genetics of pancreatic cancer has advanced spectacularly over the last 5 years so that this tumour type is now one of the best characterised of all malignancies. A small proportion of cases results from inherited predisposition due to germline transmission of a mutated CDKN2 or BRCA2 gene, while patients with familial pancreatitis due to a mutated cationic trypsinogen gene have a greatly increased risk of developing pancreatic cancer. The majority of cases are sporadic and are characterised at the molecular level by several key genetic abnormalities. The most frequent of these is point mutation of the dominant oncogene KRAS, a lesion which occurs as an early and possibly initiating event in tumourigenesis. Inactivating mutations of the tumour suppressor genes TP53, CDKN2 and SMAD4 are also frequently observed and this constellation of genetic defects sets pancreatic cancer apart from other types of cancer, a feature which could have important implications for molecular diagnosis. Genetic intervention for cancer prevention and therapy is becoming a clinical reality and several approaches are being pursued for pancreatic cancer. As well as tumour suppressor gene replacement and oncogene blockade, strategies with a potential bystander effect are showing promise. These include genetic prodrug activation therapy using selective expression of suicide genes and genetic immuno-modulation with cytokines and tumour-associated antigens.

ISSN:0012-2823    

DOI:10.1159/000201500

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Diagnosing and monitoring pancreatic cancer is an ongoing challenge. Conventional markers such as tumor-associated antigens might be supplemented by molecular markers such as gene mutations and growth factor/growth factor receptor alterations in the future. Tumor-associated antigens can easily be measured by different EIA/ELISA systems, but the analysis of gene mutations, growth factors and their receptors requires advanced molecular techniques. CA 19-9 is the most widely used conventional marker for pancreatic cancer and is a useful tool in the diagnosis and follow-up of patients after tumor resection. Nonetheless, its role in detecting early pancreatic cancer is limited. The detection of K-ras and p53 mutations, which occur in about 90 and 50% of pancreatic cancers, respectively, in blood, stool, or bile samples, seems to be a promising approach in the diagnosis. Growth factor and growth factor receptor alterations are often associated with increased tumor aggressiveness and shorter survival following tumor resection. To date the analysis of growth factors/growth factor receptors in pancreatic cancer has not entered clinical use, but further molecular characterization of pancreatic cancer is necessary for earlier and more accurate diagnosis and it may result in new treatment options.

ISSN:0012-2823    

DOI:10.1159/000201501

出版商:S. Karger AG    

年代:1997

数据来源: Karger