A phase I trial of immediate postoperative intraperitoneal floxuridine and leucovorin plus systemic 5‐fluorouracil and levamisole after resection of high risk colon cancer Journal Article


Authors: Kelsen, D. P.; Saltz, L.; Cohen, A. M.; Yao, T. J.; Enker, W.; Tong, W.; Tao, Y.; Bertino, J. R.
Article Title: A phase I trial of immediate postoperative intraperitoneal floxuridine and leucovorin plus systemic 5‐fluorouracil and levamisole after resection of high risk colon cancer
Abstract: Background. The purpose of this study was to evaluate the toxicity of immediate postoperative intraperitoneal (IP) floxuridine (FUdR) and leucovorin (LV) after resection of high risk colon cancer, and to determine the appropriate dose of intravenous fluorouracil (FU) plus levamisole during concurrent intraperitoneal therapy. Methods. The authors conducted a tertiary referral Comprehensive Cancer Center Phase I Trial in patients with resected colon cancer at high risk for recurrence. After resection of all gross disease, intraperitoneal treatment was administered twice daily for 3 days every 2 weeks for three cycles (Days 1‐3, 15‐17, 29‐31). Intravenous FU daily for 5 days was administered on days 29‐33 concurrently with the third cycle of intraperitoneal therapy. Fluorouracil doses during the last cycle of intraperitoneal therapy were escalated; intraperitoneal FUdR and LV doses and weekly intravenous FU doses (starting on Day 58) were fixed. Results. Twenty‐six patients with resected high risk colon cancer were treated. Three had Dukes' B2, 16 Dukes' C, and 7 Dukes' D (M1) resected tumors. Intraperitoneal therapy was well tolerated with no increase in operative morbidity and no operative mortality. Two patients had ⩾ Grade 3+ toxicity during IP therapy alone. There were no treatment related deaths. During concurrent intraperitoneal and intravenous chemotherapy, the maximum tolerated dose of FU was 300 mg/m2/day for 5 days. The recommended dose for Phase II or III trials is 200 mg/m2/day for 5 consecutive days. Pharmacokinetic analysis indicated that using the doses used in this trial, measurable systemic concentrations of FUdR and LV were obtained during IP therapy. This may have contributed to observed toxicity with intravenous FU doses of 300‐400 mg/m2. With a median duration of follow‐up of 18 months, four patients had recurrence of disease. No peritoneal recurrences have been noted to date. Conclusions. Immediate postoperative IP FUdR and LV are well tolerated after resection of high risk colon cancer. The recommended dose of intravenous FU beginning on Day 29 (concurrent with the last dose of IP therapy) is 5FU 200 mg/m2 for 5 consecutive days. The remaining year of adjuvant fluorouracil and levamisole can be administered with standard dose attenuation. Although follow‐up is short, the lack of recurrent peritoneal metastases is encouraging. Additional trials with this approach are warranted in patients with high risk colorectal cancer. Copyright © 1994 American Cancer Society
Keywords: adult; clinical article; controlled study; aged; middle aged; survival analysis; human cell; clinical trial; postoperative period; fluorouracil; area under the curve; diarrhea; dose response; adjuvant therapy; cancer adjuvant therapy; postoperative care; combined modality therapy; cancer staging; controlled clinical trial; neoplasm recurrence, local; bone marrow suppression; leukopenia; mucosa inflammation; stomatitis; antineoplastic combined chemotherapy protocols; carcinoembryonic antigen; colonic neoplasms; creatinine; high risk patient; bilirubin; folinic acid; colon cancer; colon resection; phase 1 clinical trial; drug half life; floxuridine; leucovorin; drug tolerance; infusions, parenteral; intraperitoneal chemotherapy; intravenous drug administration; oral drug administration; levamisole; peritonitis; intraperitoneal drug administration; humans; human; male; female; priority journal; article
Journal Title: Cancer
Volume: 74
Issue: 8
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 1994-10-15
Start Page: 2224
End Page: 2233
Language: English
DOI: 10.1002/1097-0142(19941015)74:8<2224::Aid-cncr2820740804>3.0.Co;2-a
PROVIDER: scopus c2 - 7922973
PUBMED: 7922973
DOI/URL:
Notes: Export Date: 14 January 2019 -- Article -- Source: Scopus
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MSK Authors
  1. William Ping-Yiu Tong
    136 Tong
  2. Leonard B Saltz
    616 Saltz
  3. Tzy-Jyun Yao
    57 Yao
  4. Joseph Bertino
    290 Bertino
  5. Alfred M Cohen
    187 Cohen
  6. David P Kelsen
    360 Kelsen
  7. Warren E. Enker
    38 Enker
  8. Yue Tao
    17 Tao