Circadian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma.
Sixty-eight unselected patients with progressive metastatic renal cell carcinoma (RCC) were treated between March 1985 and November 1988 with continuous infusion floxuridine (FUDR). Thirty-seven percent of these patients had previously received and failed systemic treatment. Using implantable pumps for automatic drug delivery, FUDR was continuously infused for 14 days at monthly intervals. The starting dose was 0.15 mg/kg/d (intravenous [IV]; n = 61) or 0.25 mg/kg/d (intraarterial [IA]; n = 7); IV doses were increased or decreased in increments of 0.025 mg/kg/d as permitted by toxicity. Diarrhea (with or without mild abdominal cramping) and nausea/vomiting limited the FUDR IV infusion, and hepatic function abnormalities limited FUDR IA infusion. The use of a circadian-modified infusion schedule permitted high FUDR doses to be safely given as compared with a constant rate infusion schedule. Of 63 patients assessable for response, 56 received systemic FUDR infusion. Four complete responses (CRs; 7.1%); and seven partial responses (PRs; 12.5%) were observed (objective response rate, CR plus PR, 19.6 +/- 5.1% [95% confidence limits] ). The median objective response duration was 10.8 months (range, 1 to 18 months; mean, 9.4 +/- 1.6). Four additional patients had minor tumor responses (MRs; 7.1%). In a subgroup of seven assessable patients receiving hepatic arterial FUDR, we observed one CR and three PRs (57.2 +/- 42.8%). Overall, objective response (CR plus PR) was seen in a quarter of assessable patients treated, 15 of 63, while only 15 of the 63 assessable patients (25.4%) have had objective tumor progression. The median follow-up time for all 68 patients was 28 months (range, 1 to 42), and their median survival duration is 15 months (range, 3 to 37 months). Continuous infusion FUDR is an effective outpatient treatment for progressive metastatic RCC, producing durable tumor response and causing little toxicity.
Hrushesky
W J
WJ
University of Minnesota School of Medicine, Minneapolis.
von Roemeling
R
R
Lanning
R M
RM
Rabatin
J T
JT
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002940:Circadian Rhythm; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007260:Infusion Pumps; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis
D005467:Floxuridine