Journal article
Phase I and pharmacologic studies of intraperitoneal leucovorin and 5-fluorouracil in patients with advanced cancer
Journal of clinical oncology, Vol.4(10), pp.1510-1517
10/01/1986
DOI: 10.1200/JCO.1986.4.10.1510
PMID: 3489819
Abstract
Many patients with gastrointestinal (GI) tumors develop extensive peritoneal and serosal metastasis and/or malignant ascites which respond poorly to available treatments. Twelve patients with tumors confined primarily to the intraabdominal cavity were treated with intraperitoneal (IP) 5-fluorouracil (5-FU) in escalating concentrations (2 to 4 mmol/L) in combination with leucovorin (dl-5-formyltetrahydrofolic acid or folinic acid; dl-CF) in a 2-L volume, either by eight consecutive four-hour dwells or once daily for five days. CF dose was 20.8 or 104 mumol/L. Nine of the patients had pancreatic carcinoma, one had stomach carcinoma, and two had hepatobiliary neoplasms. Median age was 62.5 years and median Eastern Cooperative Oncology Group (ECOG) performance status was 3. Toxicity included mucositis, diarrhea, nausea and vomiting, leucopenia, skin rash, and abdominal pain, and was similar to that previously reported for IP 5-FU used as a single agent. Four episodes of peritonitis occurred, but all patients responded to antibiotics. At the 20.8 mumol/L dose, dl-CF concentration in the peritoneal fluid declined from 10.4 +/- 3.0 3.0 mumol/L at one hour to 4.9 +/- 2.2 mumol/L at four hours, corresponding to a mean absorption half-life of 127 +/- 49 minutes and a mean peritoneal clearance of 13.0 +/- 4.5 mL/min. Decline was biphasic in all but five of the 19 exchanges evaluated. The levels of l-CF (biologically active isomer of dl-CF) were 2.8 +/- 2.5 mumol/L after 60 minutes and 1.2 +/- 0.7 mumol/L after four hours. The peritoneal area under the concentration v time curve (AUC) for 5-FU increased proportionally with dose. For example, the AUC at 2.0 and 3.5 mmol/L was 129 +/- 25 and 201 +/- 23 mmol/L X minute, respectively. However, the maximal peritoneal to plasma AUC ratio was 461 at the 2 mmol/L dose, but decreased with increasing doses as systemic clearance decreased. This regimen was well tolerated in patients with advanced cancer, but must be evaluated further to determine its clinical efficacy.
Details
- Title: Subtitle
- Phase I and pharmacologic studies of intraperitoneal leucovorin and 5-fluorouracil in patients with advanced cancer
- Creators
- S G ArbuckF TraveH O DouglassH NavaS ZakrzewskiY M Rustum
- Resource Type
- Journal article
- Publication Details
- Journal of clinical oncology, Vol.4(10), pp.1510-1517
- DOI
- 10.1200/JCO.1986.4.10.1510
- PMID
- 3489819
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 10/01/1986
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360059502771
Metrics
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