Abstract
Patients with locally advanced pancreatic adenocarcinoma who receive conventional therapy with radiation with 5-fluorouracil (5-FU) have median survivals ranging from 8 to 12 months. Here we report our experience with a four-drug chemotherapeutic regimen that resulted in sufficient downstaging of tumor in some patients to justify surgical reexploration and resection. From April 1991 through April 1994, 38 patients received 5-FU as a continuous infusion (200 mg/m2/day), calcium leucovorin weekly by intravenous bolus injection (30 mg/m2), mitomycin-C every 6 weeks (10 mg/m2 intravenously), and dipyridamole daily orally (75 mg) for locally advanced unresected pancreatic cancer. All of these patients were evaluable for response, toxicity, and survival. There were 14 partial responses and one complete response--a 39% response rate. The median survival for all patients was 15.5 months; the 1-year survival rate from time of initial diagnosis was 70%. Six of 15 responding patients had sufficient tumor regression to meet clinical criteria for resectability and reexploration, four of whom underwent a curative resection. The median survival of these six patients was 28 months from the time of original diagnosis. The 1-year survival was 83%, with one patient still alive and free of disease at 53 months. We believe this unique experience from a single institution justifies a prospective multi-institutional trial to evaluate the efficacy of this approach in a larger number of patients.
MeSH Terms
Administration, Oral
Adult
Aged
Aged, 80 and over
Antibiotics, Antineoplastic/administration & dosage,adverse effects
Antidotes/administration & dosage
Antimetabolites, Antineoplastic/administration & dosage,adverse effects
Antineoplastic Combined Chemotherapy Protocols/administration & dosage,adverse effects,therapeutic use
Combined Modality Therapy
Dipyridamole/administration & dosage,adverse effects
Disease-Free Survival
Female
Fluorouracil/administration & dosage,adverse effects
Humans
Infusions, Intravenous
Injections, Intravenous
Leucovorin/administration & dosage
Male
Middle Aged
Mitomycin/administration & dosage,adverse effects
Neoplasm Staging
Pancreatectomy
Pancreatic Neoplasms/drug therapy,pathology,surgery
Phosphodiesterase Inhibitors/administration & dosage,adverse effects
Prospective Studies
Remission Induction
Survival Rate
Chemicals
Antibiotics, Antineoplastic
Antidotes
Antimetabolites, Antineoplastic
Phosphodiesterase Inhibitors
Mitomycin
Dipyridamole
Leucovorin
Fluorouracil
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Todd K E
Department of Surgery, UCLA School of Medicine, Los Angeles, CA, USA.
Gloor B
Lane J S
Isacoff W H
Reber H A
References (17)
17 references, click to expand
-
The feedback inhibition of thymidine kinase.
Biochim Biophys Acta. 1963 Jan 8;67:153-5
PMID: 14015204
-
Effect of 5, 10-methylenetetrahydrofolate on the dissociation of 5-fluoro-2'-deoxyuridylate from thymidylate synthetase: evidence for an ordered mechanism.
Biochemistry. 1978 Sep 19;17(19):4018-24
PMID: 101234
-
Augmentation of methotrexate cytotoxicity in human colon cancer cells achieved through inhibition of thymidine salvage by dipyridamole.
Biochem Pharmacol. 1987 Mar 15;36(6):809-14
PMID: 3566784
-
Overview of current status and future direction of clinical trials with 5-fluorouracil in combination with folinic acid.
Cancer Treat Rep. 1987 Dec;71(12):1249-64
PMID: 3319136
-
Fluorouracil and high-dose leucovorin in previously untreated patients with advanced adenocarcinoma of the pancreas: results of a phase II trial.
J Clin Oncol. 1991 Dec;9(12):2128-33
PMID: 1960554
-
Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A Phase II Study.
Cancer. 1993 Oct 1;72(7):2124-33
PMID: 8374871
-
Biochemical modulation of fluorouracil by dipyridamole: preclinical and clinical experience.
Semin Oncol. 1992 Apr;19(2 Suppl 3):56-65
PMID: 1557658
-
Epidemiology of and risk factors for pancreatic cancer.
Surg Clin North Am. 1995 Oct;75(5):819-43
PMID: 7660248
-
Time-dependent interactions between 5-fluorouracil and mitomycin C on a human colon carcinoma cell line, HCT-8, in vitro.
Eur J Cancer Clin Oncol. 1989 Mar;25(3):571-2
PMID: 2495221
-
Effect of excess folates and deoxyinosine on the activity and site of action of 5-fluorouracil.
Cancer Res. 1981 Sep;41(9 Pt 1):3288-95
PMID: 6973389
-
A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study.
J Clin Oncol. 1989 Apr;7(4):425-32
PMID: 2926468
-
Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer.
Lancet. 1969 Oct 25;2(7626):865-7
PMID: 4186452
-
Feedback inhibition of thymodine kinase by thymodine triphosphate.
J Biol Chem. 1963 Apr;238:1467-74
PMID: 13964236
-
Pharmacokinetics of fluorouracil in humans.
Cancer Res. 1978 Oct;38(10):3479-82
PMID: 688233
-
Preoperative irradiation in carcinoma of the pancreas.
Cancer. 1980 Nov 1;46(9):1945-9
PMID: 7427900
-
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 + 5-fluorouracil: The Gastrointestinal Tumor Study Group.
Cancer. 1981 Oct 15;48(8):1705-10
PMID: 7284971
-
Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project.
J Clin Oncol. 1992 Jun;10(6):896-903
PMID: 1534121