Review article: current treatment and optimal patient management in pancreatic cancer

Abstract

This review analyses the current state of knowledge and understanding concerning the optimum treatment and therapeutic management of patients who suffer from pancreatic cancer. It outlines recent advances in scientific understanding and assesses their potential future value to clinicians in confronting this disease. Despite a significant expansion in scientific knowledge relating to factors underlying the early development of pancreatic carcinoma, the clinician continues to be restricted to a severely limited therapeutic armoury for this disease. Local therapies (surgery and radiation) are inevitably of limited value in the face of a disease that is normally encountered at a stage where metastasis is already highly developed. Despite such limitations, however, surgery performed in specialist units may be of value for 10-20% of patients, with a 5-year survival rate in such units of between 10 and 24%. This may be improved even further by appropriate use of adjuvant treatment. The advanced stage of the disease when normally encountered emphasizes the potential value of systemic treatment in this therapeutic area. Unfortunately systemic treatment (chemotherapy) has been found to be ineffective to date in significantly extending survival, with a low rate and duration of remission being identified in most trials. The challenge for both the health service and the pharmaceutical industry is to harness recent and future developments in scientific knowledge to the practical benefit of clinicians. Where cure is possible it should be vigorously pursued; where it is not, in this field above all others, clinicians have a duty of care. To achieve this it is necessary to abandon the therapeutic nihilism that has characterized the attitudes of clinicians towards this disease in the past. It is time that such nihilism was replaced by a recognition of the challenges and the opportunities available to clinicians in enhancing the quantity and quality of life available to patients. The dictum of 'curing whenever possible but caring always' should be the future therapeutic philosophy used to guide clinicians in this important and rapidly changing therapeutic area.

Adjuvant Therapy for Pancreatic Cancer

“…The addition of other modulators such as phosphonacetyl-L-aspartate (PALA), and interferon has also not produced significant improvements in survival [34,35] . Comparisons of 5-FU alone and 5-FU with a combination of other agents have not shown any advantage for the combination groups in randomized trials [33] .…”

Chemotherapy for pancreatic cancer

“…5-Fluorouracil: Until the development of gemcitabine only 5-fluorouracil (5-FU) and mitomycin C had consistently shown a beneficial effect. 8,25,26 5-FU is an S-phase-specific, fluorinated pyrimidine that is metabolised intracellularly to its active form fluorodeoxyuridine monophosphate (FdUMP) via the de novo pyrimidine pathway; [27][28][29][30][31] see Figure 1.…”

“…[10][11][12][13] Post-operative mortality has also been dramatically reduced in specialist high-volume centres from over 20% to less than 6%. 8 After successful surgery the prognosis is still relatively poor (median and 5-year survivals of around 13-15 months and 15-20%, respectively, [14][15][16][17][18] but is far superior in specialist centres. 8,13,19 With this increasing success there has also been greater attention focused towards adjuvant and neo-adjuvant chemotherapy.…”

“…8 After successful surgery the prognosis is still relatively poor (median and 5-year survivals of around 13-15 months and 15-20%, respectively, [14][15][16][17][18] but is far superior in specialist centres. 8,13,19 With this increasing success there has also been greater attention focused towards adjuvant and neo-adjuvant chemotherapy. This article examines the current thinking and evidence for the use of chemotherapy and how it compares to other forms of treatment for pancreatic cancer.…”

“…Pancreatic cancer is aggressive and presents with disseminated or locally advanced disease due to its relatively asymptomatic nature during its early course. [1][2][3][4][5][6][7][8][9] The median survival for all stages of pancreatic cancer is less than 3-5 months from diagnosis, with a 5-year survival of 0.4-3%. 1,7,9 Surgery is the only treatment that offers the prospect of cure, although at present this is more hope than reality.…”