| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute [J. L. S., M. F. B., A. R. B., H. L., V. T. D., C. E. M.], and Division of Research Services [J. M. C., R. L. D.], NIH, Bethesda, Maryland 20205
A Phase I study was conducted of 5-fluorouracil administered i.p. in a 2-liter volume of 1.5% Inpersol. The drug was administered via Tenckhoff peritoneal dialysis catheters to ten patients with tumors confined to the i.p. space. Dialysis concentrations ranged from 5 µM to 8 mM. Complications of the dialysis procedure alone included mild abdominal discomfort and 2 cases of gram-negative bacterial peritonitis, both easily controlled with antibiotics. 5-Fluorouracil caused the same pattern of toxicity as when administered by other routes. There was no local or central nervous system toxicity. Dose-limiting toxicity included pancytopenia and mucositis at a dialysis concentration of 4.5 to 5 mM administered for eight consecutive 4-hr exchanges. There were two documented responses in eight evaluable patients.
5-Fluorouracil concentrations were measured by high-pressure liquid chromatography. Peritoneal fluid concentrations decline in a first-order fashion with a half-life of 1.6 hr. The mean permeability area product was 14 ml/min. A mean of 82% of drug was absorbed in 4 hr. Plasma levels rise over the first 30 to 45 min and decline in a nonlinear fashion. Plasma levels are substantially lower than are peritoneal fluid levels. Mean 4-hr peritoneal fluid concentration was 298 times the simultaneously measured plasma levels. Total body clearance ranged from 0.9 to 15 liters/min and declined with increasing dialysate concentration.
We conclude the i.p. route is a relatively safe way to deliver high concentrations and large amounts of drug to the i.p. cavity with a significant pharmacological advantage over conventional routes of administration.
1 To whom requests for reprints should be addressed, at Clinical Pharmacology Branch, Building 10, Room 6N102, National Cancer Institute, NIH, Bethesda, Md. 20205.
2 Present address: Department of Community and Environmental Medicine, University of California at Irvine, Irvine, Calif. 92717.
3 Present address: Oakdale Medical Building, Robbinsdale, Minn. 55422.
Received 6/18/79. Accepted 11/20/79.
This article has been cited by other articles:
|
|
 |
|
  J. H. Stewart IV, P. Shen, G. B. Russell, R. F. Bradley, J. C. Hundley, B. L. Loggie, K. R. Geisinger, and E. A. Levine Appendiceal Neoplasms With Peritoneal Dissemination: Outcomes After Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy Ann. Surg. Oncol., May 1, 2006; 13(5): 624 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Stewart IV, P. Shen, and E. A. Levine Intraperitoneal Hyperthermic Chemotherapy for Peritoneal Surface Malignancy: Current Status and Future Directions Ann. Surg. Oncol., October 1, 2005; 12(10): 765 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Ewens, E. Mihich, and M. J. Ehrke Fluorouracil Plus Leucovorin Induces Submandibular Salivary Gland Enlargement in Rats Toxicol Pathol, June 1, 2005; 33(4): 507 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pilati, S. Mocellin, C. R. Rossi, M. Foletto, L. Campana, D. Nitti, and M. Lise Cytoreductive Surgery Combined With Hyperthermic Intraperitoneal Intraoperative Chemotherapy for Peritoneal Carcinomatosis Arising From Colon Adenocarcinoma Ann. Surg. Oncol., June 1, 2003; 10(5): 508 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R Vocelka, D. L Anderson, and G. I Crockett Hyperthermic intraoperative intraperitoneal chemotherapy for peritoneal carcinomatosis and sarcomatosis using a cardioplegia heat exchanger and a two-pump system: a case report Perfusion, December 1, 2000; 15(6): 549 - 552. [Abstract] [PDF]
|
|
|
|
 |
|
 B. Rashidi, Z. An, F.-X. Sun, A. R. Moossa, and R. M. Hoffman Antimetastatic Intraoperative Chemotherapy of Human Colon Tumors in the Livers of Nude Mice Clin. Cancer Res., June 1, 2000; 6(6): 2464 - 2468. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. B. Saltz and N. E. Kemeny Adjuvant Chemotherapy of Colorectal Cancer Oncologist, February 1, 1996; 1(1): 22 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Regelson Review: Advances in Intraperitoneal (Intracavitary) Administration of Synthetic Polymers for Immunotherapy and Chemotherapy Journal of Bioactive and Compatible Polymers, January 1, 1986; 1(1): 84 - 107. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
