Treatment of metastatic renal cell carcinoma with constant-rate floxuridine infusion plus recombinant alpha 2b-interferon.

Abstract

BACKGROUND:

Floxuridine (FUDR) and alpha-interferon (IFN) are active agents in advanced renal cell carcinoma, with different dose-limiting toxic effects and antitumor synergism in experimental models. The main purpose of this phase II study was to assess the activity and toxic effects of a combination of FUDR and alpha 2b-IFN in metastatic renal cell carcinoma.

PATIENTS AND METHODS:

Metastatic renal cell carcinoma patients with measurable disease entered the study. FUDR was administered as a constant-rate continuous infusion for 14 days every 28 days at a starting daily dose of 0.1 mg/kg and with dose escalations of 0.025 mg/kg/day at each subsequent cycle if WHO > or = 2 toxicity had not occurred. IFN-alpha 2b 10 x 10(6) I.U. was administered intramuscularly 3 times per week.

RESULTS:

Forty-two patients entered the study and a total of 272 cycles of FUDR + alpha 2b-IFN were administered. In 41 evaluable patients WHO grade III-IV toxic effects included nausea and vomiting (22%), diarrhea (32%), stomatitis (12%), fatigue (27%) and anorexia (12%). It was possible to increase the initial FUDR does in 21 (50%) patients; the median FUDR dose intensity was 0.35 mg/kg/week (range 0.18-0.54). Among 39 evaluable patients, 3 (7.5%) complete and 10 (25.5%) partial responses were observed (response rate 33%, 95% confidence interval (CI) 19%-50%) which lasted a median of 13 months (5.5-40+). Responses also occurred in liver (2), in patients pretreated with systemic therapy (5) and in patients who had other unfavourable prognostic characteristics (7). Median progression-free and survival times were 9 and 16 months, respectively.

CONCLUSIONS:

In this study FUDR + alpha 2b-IFN demonstrated interesting activity in metastatic renal cell carcinoma, showing promise also in patients with unfavourable prognostic characteristics. The antitumor activity of FUDR and alpha 2b-IFN seems to be cumulative, but cumulative toxicity is also observed. These results require confirmation in randomised trials.

• Authors: A Falcone, C Cianci, E Pfanner, S Ricci, M Lencioni, I Brunetti, P C Giulianotti, L Vannucci, F Mosca, P F Conte
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 7 Issue 6 Pg. 601-5 (Aug 1996) ISSN: 0923-7534 [Print] England
• PMID: 8879374 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Floxuridine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Renal Cell (drug therapy)
• Drug Administration Schedule
• Drug Synergism
• Female
• Floxuridine (administration & dosage)
• Humans
• Infusions, Intravenous
• Injections, Intramuscular
• Interferon alpha-2
• Interferon-alpha (administration & dosage)
• Kidney Neoplasms (drug therapy)
• Male
• Middle Aged
• Neoplasm Metastasis
• Recombinant Proteins