Phase II trial of branched peginterferon-α 2a (40 kDa) for patients with advanced renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Rakhit, A.; Thompson, J.; Gurney, H.; Selby, P.; Figlin, R.; Negrier, S.; Ernst, S.; Siebels, M.; Ginsberg, M.; Rittweger, K.; Hooftman, L. |
| Article Title: | Phase II trial of branched peginterferon-α 2a (40 kDa) for patients with advanced renal cell carcinoma |
| Abstract: | Background: Peginterferon-α 2a (40 kDa), PEGASYS™ (PEG-IFN), is a modified form of recombinant human interferon (IFN)-α 2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase II trial was conducted in previously untreated patients with advanced renal cell carcinoma (RCC) to assess efficacy, toxicity and pharmacokinetic profile. Patients and methods: Forty previously untreated patients with advanced RCC were enrolled on this multicenter trial. The median age was 60 years and 63% had prior nephrectomy. PEG-IFN was administered at a dose of 450 μg/week on a weekly basis by subcutaneous injection. Serial venous blood samples were drawn to assess concentrations of PEG-IFN. Results: Five (13%) patients achieved a major response (four partial and one complete). The median time to progression was 3.8 months, and 63% of patients were alive at 1 year. The toxicity profile was mostly mild to moderate in intensity. Toxicity higher than grade 2 included neutropenia (six patients), fatigue/asthenia (four patients), nausea/vomiting (three patients) and elevated hepatic transaminase concentrations (four patients). Serum drug levels were studied in all patients; mean Cmax at week 1 was 19 ng/ml, and levels were sustained at close to peak over 1 week. With chronic dosing, drug concentration was increased 3-fold, and steady state was achieved in 5-9 weeks. Conclusions: The sustained maintenance of serum levels of PEG-IFN allows once-weekly dosing. The efficacy and tolerability profile was qualitatively similar to standard IFN-α, and adverse events were mostly mild to moderate in nature. |
| Keywords: | adult; cancer survival; clinical article; controlled study; treatment outcome; aged; middle aged; survival rate; clinical trial; drug tolerability; fatigue; neutropenia; advanced cancer; dose response; drug efficacy; follow-up studies; neoplasm staging; controlled clinical trial; phase 2 clinical trial; steady state; thrombocytopenia; drug administration schedule; dose-response relationship, drug; renal cell carcinoma; kidney carcinoma; kidney neoplasms; nephrectomy; risk assessment; alanine aminotransferase blood level; asthenia; alanine aminotransferase; depression; rigor; carcinoma, renal cell; biopsy, needle; multicenter study; taste disorder; nausea and vomiting; neoplasm invasiveness; drug absorption; drug blood level; drug half life; injections, subcutaneous; half-life; mood disorder; biological availability; drug formulation; qualitative analysis; kidney function tests; interferon-α; recombinant alpha2a interferon; recombinant alpha2b interferon; angina pectoris; venous blood; interferon alfa-2a; peginterferon alpha2a; humans; human; male; female; priority journal; article; pegylated; intron (tm); 2',5'-oligoadenylate synthetase; neopterin |
| Journal Title: | Annals of Oncology |
| Volume: | 13 |
| Issue: | 11 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2002-11-01 |
| Start Page: | 1799 |
| End Page: | 1805 |
| Language: | English |
| DOI: | 10.1093/annonc/mdf288 |
| PUBMED: | 12419754 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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