A phase II study of weekly 24-hour infusion with high-dose fluorouracil with leucovorin in colorectal carcinoma

Bach Ardalan, Lucy Chua, Er Ming Tian, Rajender Reddy, Kasi Sridhar, Pasquale W Benedetto, Stephen P Richman, Adrian Legaspi, Stuart Waldman, Louise Morrell, Lynn G Feun, Niramol Savaraj, Alan Livingstone

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Abstract

Twenty-two patients with advanced colorectal carcinoma were enrolled in this study. Ten patients had received prior chemotherapy that included the combination of fluorouracil (5-FU) and leucovorin (LV). All patients required subcutaneous port insertion and portable external infusion pumps to allow outpatient treatment. 5-FU (2,600 mg/m2) was administered concurrently with LV (500 mg/m2) over 24 hours of continuous infusion. The mean steady-state plasma concentration of 5-FU was 10 μmol/L (range, 7 to 14 μmol/L). The 5-FU dose was based on our previous phase I study, in which maximum-tolerated dose (MTD) of 5-FU was determined to be 2,600 mg/m2 in combination with a fixed dose of LV at 500 mg/m2. The treatment was repeated weekly. Twenty-two patients received a total of 560 courses of treatment. Eleven instances of grade 2-3 toxicity were observed: diarrhea (five), stomatitis (three), hand/foot syndrome (three). The overall objective response was 45% (10 of 22) and among previously untreated patients was 58%. Three of the responders achieved complete response (CR), with lung and liver as the metastatic sites. The median duration of survival for the previously untreated patients was not reached at 22 months, and was 10 months for the previously treated patients. These results suggest that short-term infusional therapy of 5-FU and LV in patients with advanced metastatic colorectal cancer generates acceptable toxicity, with equivalent or superior survivability in previously treated and untreated patients versus alternate methods of administration of the two agents.

Original languageEnglish
Pages (from-to)625-630
Number of pages6
JournalJournal of Clinical Oncology
Volume9
Issue number4
StatePublished - Dec 1 1991

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Leucovorin
Fluorouracil
Colorectal Neoplasms
Hand-Foot Syndrome
Infusion Pumps
Stomatitis
Maximum Tolerated Dose
Therapeutics
Combination Drug Therapy
Diarrhea
Outpatients
Lung
Survival
Liver

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A phase II study of weekly 24-hour infusion with high-dose fluorouracil with leucovorin in colorectal carcinoma. / Ardalan, Bach; Chua, Lucy; Tian, Er Ming; Reddy, Rajender; Sridhar, Kasi; Benedetto, Pasquale W; Richman, Stephen P; Legaspi, Adrian; Waldman, Stuart; Morrell, Louise; Feun, Lynn G; Savaraj, Niramol; Livingstone, Alan.

In: Journal of Clinical Oncology, Vol. 9, No. 4, 01.12.1991, p. 625-630.

Research output: Contribution to journalArticle

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AB - Twenty-two patients with advanced colorectal carcinoma were enrolled in this study. Ten patients had received prior chemotherapy that included the combination of fluorouracil (5-FU) and leucovorin (LV). All patients required subcutaneous port insertion and portable external infusion pumps to allow outpatient treatment. 5-FU (2,600 mg/m2) was administered concurrently with LV (500 mg/m2) over 24 hours of continuous infusion. The mean steady-state plasma concentration of 5-FU was 10 μmol/L (range, 7 to 14 μmol/L). The 5-FU dose was based on our previous phase I study, in which maximum-tolerated dose (MTD) of 5-FU was determined to be 2,600 mg/m2 in combination with a fixed dose of LV at 500 mg/m2. The treatment was repeated weekly. Twenty-two patients received a total of 560 courses of treatment. Eleven instances of grade 2-3 toxicity were observed: diarrhea (five), stomatitis (three), hand/foot syndrome (three). The overall objective response was 45% (10 of 22) and among previously untreated patients was 58%. Three of the responders achieved complete response (CR), with lung and liver as the metastatic sites. The median duration of survival for the previously untreated patients was not reached at 22 months, and was 10 months for the previously treated patients. These results suggest that short-term infusional therapy of 5-FU and LV in patients with advanced metastatic colorectal cancer generates acceptable toxicity, with equivalent or superior survivability in previously treated and untreated patients versus alternate methods of administration of the two agents.

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