TY - JOUR
T1 - Phase I study of 5-fluorouracil administered by protracted venous infusion, leucovorin, and pelvic radiation therapy
AU - Martenson, James A.
AU - Shanahan, Thomas G.
AU - O'Connell, Michael J.
AU - Cobau, Charles D.
AU - Schroeder, Georgene
AU - Burch, Patrick A.
AU - Levitt, Ralph
AU - Rowland, Kendrith M.
PY - 1999/8/15
Y1 - 1999/8/15
N2 - BACKGROUND. This study was designed to assess the toxicity of pelvic radiation therapy, 5-fluorouracil (5-FU) administered by protracted venous infusion, and leucovorin. METHODS. Pelvic radiation therapy consisted of 50.4-54 gray (Gy) administered in 28-30 fractions. Systemic treatment consisted of leucovorin (10 mg daily) administered orally and protracted venous infusion of 5-FU. The initial daily 5-FU dose was 150 mg/m2. Dose escalations were planned in increments of 25 mg/m2. RESULTS. Forty eligible patients were registered, of whom 37 were evaluable for chemoradiotherapy- related toxicity. Grade 3 or 4 toxicity secondary to radiation therapy, protracted venous infusion of 5-FU, and leucovorin occurred in 2 of 17 patients at a daily 5-FU dose of 150 mg/m2, in 5 of 10 patients at a daily 5-FU dose of 175 mg/m2, and in 5 of 10 patients at a daily 5-FU dose of 200 mg/m2. Diarrhea was dose-limiting in 7 of 8 patients with Grade 4 toxicity. Venous thrombosis, a treatment-related complication not directly related to chemotherapy or radiation therapy, occurred in 5 of the 40 patients entered into this study. Four thromboses occurred at the site of a central catheter. No thrombotic complications occurred in the last 7 patients, who were given warfarin orally (1 mg daily) during treatment. CONCLUSIONS. Toxicity due to radiation therapy, protracted venous infusion of 5-FU, and leucovorin when 5- FU is given daily at a dose of 150 mg/m2 is similar to that observed in current chemoradiotherapy regimens for patients with rectal carcinoma. This regimen will be considered as a possible investigational treatment arm of a future trial of adjuvant therapy for rectal carcinoma patients.
AB - BACKGROUND. This study was designed to assess the toxicity of pelvic radiation therapy, 5-fluorouracil (5-FU) administered by protracted venous infusion, and leucovorin. METHODS. Pelvic radiation therapy consisted of 50.4-54 gray (Gy) administered in 28-30 fractions. Systemic treatment consisted of leucovorin (10 mg daily) administered orally and protracted venous infusion of 5-FU. The initial daily 5-FU dose was 150 mg/m2. Dose escalations were planned in increments of 25 mg/m2. RESULTS. Forty eligible patients were registered, of whom 37 were evaluable for chemoradiotherapy- related toxicity. Grade 3 or 4 toxicity secondary to radiation therapy, protracted venous infusion of 5-FU, and leucovorin occurred in 2 of 17 patients at a daily 5-FU dose of 150 mg/m2, in 5 of 10 patients at a daily 5-FU dose of 175 mg/m2, and in 5 of 10 patients at a daily 5-FU dose of 200 mg/m2. Diarrhea was dose-limiting in 7 of 8 patients with Grade 4 toxicity. Venous thrombosis, a treatment-related complication not directly related to chemotherapy or radiation therapy, occurred in 5 of the 40 patients entered into this study. Four thromboses occurred at the site of a central catheter. No thrombotic complications occurred in the last 7 patients, who were given warfarin orally (1 mg daily) during treatment. CONCLUSIONS. Toxicity due to radiation therapy, protracted venous infusion of 5-FU, and leucovorin when 5- FU is given daily at a dose of 150 mg/m2 is similar to that observed in current chemoradiotherapy regimens for patients with rectal carcinoma. This regimen will be considered as a possible investigational treatment arm of a future trial of adjuvant therapy for rectal carcinoma patients.
KW - 5-fluorouracil
KW - Leucovorin
KW - Pelvic radiation therapy
KW - Protracted venous infusion
KW - Rectal carcinoma
UR - http://www.scopus.com/inward/record.url?scp=0033567069&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033567069&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0142(19990815)86:4<710::AID-CNCR21>3.0.CO;2-5
DO - 10.1002/(SICI)1097-0142(19990815)86:4<710::AID-CNCR21>3.0.CO;2-5
M3 - Article
C2 - 10440700
AN - SCOPUS:0033567069
SN - 0008-543X
VL - 86
SP - 710
EP - 714
JO - Cancer
JF - Cancer
IS - 4
ER -