Chemotherapy for pancreatic cancer

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Abstract

To date, no satisfactory treatment has been developed for treatment of patients with advanced pancreatic carcinoma. The median survival of these patients is only three to six months. Of more than 30 agents evaluated over the past three decades, only 5-FU results in a response rate with 95% confidence intervals greater than 20%. Most responses are partial, of short duration, and of questionable clinical benefit. To date, efforts to improve response rates by biochemical modulation of 5-FU have been unsuccessful but additional studies are warranted and are ongoing. Although improved response rates have been reported with some drug combinations, such as streptozotocin, mitomycin and 5-FU (SMF), median survival for combination therapy is no better than that attained with single-agent therapy. Current therapeutic options for patients with advanced disease include 5-FU, supportive care, or investigational treatment in a clinical trial.

In three out of four studies, patients with locally advanced pancreatic carcinoma who received combined modality therapy (radiation in combination with 5-FU) survived significantly longer than those treated with either radiation or chemotherapy alone. The brief survival advantage, however, must be considered in the context of the additional toxicity and treatment time required for the combined modality treatment.

Radiotherapy in combination with 5-FU should be considered standard adjuvant therapy for patients with completely resected disease. The median survival of treated patients was 20 months and significantly longer than the surgery alone control group (11 months) (Kalser and Ellenberg, 1985; GITSG, 1987). Of greatest significance is the tail-end plateau on the survival curve suggesting that approximately 18% of patients who received combined modality therapy were cured.

The results with currently available treatment for all stages of disease are poor; therefore, patients should be informed about ongoing clinical trials which may someday improve the prognosis for pancreatic cancer.

References (56)

  • SK Carter et al.

    The integration of chemotherapy into a combined modality approach for cancer treatment. VI. Pancreatic adenocarcinoma

    Cancer Treatment Reviews

    (1975)
  • CG Moertel et al.

    Combined 5-fluorouracil and supervoltage radiation therapy for locally unresectable gastrointestinal cancers

    Lancet

    (1969)
  • JA Ajani et al.

    Ifosfamide and mesna: marginally active in patients with advanced carcinoma of the pancreas

    Journal of Clinical Oncology

    (1988)
  • JR Anderson et al.

    Analysis of survival by tumor response

    Journal of Clinical Oncology

    (1983)
  • SG Arbuck

    5-FU/Leucovorin-biochemical modulation that works?

    Oncology

    (1987)
  • SG Arbuck

    Overview of clinical trials using 5-FU and leucovorin for the treatment of colorectal cancer

    Cancer

    (1989)
  • JS Barkin et al.

    The evaluation of CT and sonographic pancreatic measurements in determining tumor response

  • S Bernard et al.

    A Phase II study of ifosfamide (ifos) plus n-acetylcysteine (NAC) in metastatic measurable pancreatic adenocarcinoma (PC)

  • JD Bitran et al.

    Treatment of metastatic pancreatic and gastric adenocarcinomas with 5-fluorouracil, adriamycin and mitomycin C (FAM)

    Cancer Treatment Reports

    (1979)
  • MF Brennan et al.

    Cancer of the pancreas

  • HW Bruckner et al.

    Leucovorin and 5-fluorouracil as a treatment for disseminated cancer of the pancreas and unknown primary tumors

    Cancer Research

    (1988)
  • P Bruhl et al.

    Results obtained with fractionated ifosfamide massive-dose treatment in generalized malignant tumors

    International Journal of Clinical Pharmacology

    (1976)
  • RM Bukowski et al.

    Phase II trial of streptozotocin, mitomycin-c and 5-fluorouracil in adenocarcinoma of the pancreas

    Cancer Clinical Trials

    (1980)
  • RM Bukowski et al.

    Phase II trial of 5-fluorouracil, adriamycin, mitomycin-C and streptozotocin (FAM-S) in pancreatic carcinoma

    Cancer

    (1982)
  • RM Bukowski et al.

    Randomized trial of 5-fluorouracil and mitomycin C with or without streptozotocin for advanced pancreatic cancer. A Southwest Oncology Group Study

    Cancer

    (1983)
  • DS Childs et al.

    Treatment of malignant neoplasms of the gastrointestinal tract with a combination of 5-fluorouracil and radiation

  • SA Cullinan et al.

    A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma

    Journal of the American Medical Association

    (1985)
  • S Cullinan et al.

    A Phase III evaluation of drug combinations in the therapy of advanced pancreatic cancer

  • JA Decaprio et al.

    Phase II study of weekly 5-fluorouracil (5FU) and folinic acid (FA) in previously untreated patients with unresectable measurable pancreatic adenocarcinoma

  • J Dougherty et al.

    Phase I-II study of cisplatin (P), high-dose Ara-C (A) and caffeine (C) (CAC) in advanced adenocarcinoma of the pancreas

  • RM Evans et al.

    Effect of excess folates and deoxyinosine on the activity and site of action of 5-fluorouracil

    Cancer Research

    (1981)
  • L Elias et al.

    Interferon effects upon the adenocarcinoma 38 and HL-60 cell lines: antiproliferative responses and synergistic interactions with halogenated pyrimidine antimetabolites

    Cancer Research

    (1988)
  • N Gad-Ei-Mawla et al.

    Ifosfamide treatment of pancreatic cancer

    Cancer Treatment Reports

    (1981)
  • Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil) and high dose radiation and 5-fluorouracil

    Cancer

    (1981)
  • Phase II studies of drug combinations in advanced pancreatic carcinoma: fluorouracil plus doxorubicin plus mitomycin-C and two regimens of streptozotocin plus mitomycin-C plus fluorouracil

    Journal of Clinical Oncology

    (1986)
  • Further evidence of effective adjuvant combined radiation; chemotherapy following curative resection of pancreatic cancer

    Cancer

    (1987)
  • Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone

    Journal of the National Cancer Institute

    (1988)
  • Ifosfamide is an inactive substance in the treatment of pancreatic carcinoma

    Cancer

    (1989)
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