Abstract
Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via an implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8–14 of therapy, patients received IdUrd as a separate 3-h HAI daily × 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day × 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2″-deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (≤0.1 μm). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day × 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day × 7.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6437-6442 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 49 |
| Issue number | 22 |
| State | Published - Nov 15 1989 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
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Phase I Trial of Hepatic Artery Infusion of 5-Iodo-2″-deoxyuridine and 5-Fluorouracil in Patients with Advanced Hepatic Malignancy : Biochemically Based Combination Chemotherapy. / Remick, Scot C.; Benson III, Al B; Weese, James L.; Willson, James K.V.; Ramirez, Guillermo; Wirtanen, George W.; Alberti, Dona B.; Nieting, Lavonne M.; Tutsch, Kendra D.; Fischer, Paul H.; Trump, Donald L.
In: Cancer Research, Vol. 49, No. 22, 15.11.1989, p. 6437-6442.Research output: Contribution to journal › Article
TY - JOUR
T1 - Phase I Trial of Hepatic Artery Infusion of 5-Iodo-2″-deoxyuridine and 5-Fluorouracil in Patients with Advanced Hepatic Malignancy
T2 - Biochemically Based Combination Chemotherapy
AU - Remick, Scot C.
AU - Benson III, Al B
AU - Weese, James L.
AU - Willson, James K.V.
AU - Ramirez, Guillermo
AU - Wirtanen, George W.
AU - Alberti, Dona B.
AU - Nieting, Lavonne M.
AU - Tutsch, Kendra D.
AU - Fischer, Paul H.
AU - Trump, Donald L.
PY - 1989/11/15
Y1 - 1989/11/15
N2 - Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via an implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8–14 of therapy, patients received IdUrd as a separate 3-h HAI daily × 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day × 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2″-deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (≤0.1 μm). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day × 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day × 7.
AB - Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via an implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8–14 of therapy, patients received IdUrd as a separate 3-h HAI daily × 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day × 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2″-deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (≤0.1 μm). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day × 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day × 7.
UR - http://www.scopus.com/inward/record.url?scp=0024310434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024310434&partnerID=8YFLogxK
M3 - Article
C2 - 2804987
AN - SCOPUS:0024310434
VL - 49
SP - 6437
EP - 6442
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 22
ER -