Could interferon still play a role in metastatic renal cell carcinoma? A randomized study of two schedules of sorafenib plus interferon-alpha 2a (RAPSODY).

Abstract

BACKGROUND:

Sorafenib has proven efficacy in metastatic renal cell carcinoma (mRCC). Interferon (IFN) has antiangiogenic activity that is thought to be both dose- and administration-schedule dependent.

OBJECTIVE:

To compare two different schedules of IFN combined with sorafenib.

DESIGN, SETTING, AND PARTICIPANTS:

Single-stage, prospective, noncomparative, randomized, open-label, multicenter, phase 2 study on previously untreated patients with mRCC and Eastern Cooperative Oncology Group performance status 0-2.

INTERVENTION:

Sorafenib 400mg twice daily plus subcutaneous IFN, 9 million units (MU) three times a week (Arm A) or 3 MU five times a week (Arm B).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Primary end points were progression-free survival (PFS) for each arm and safety. Data were evaluated according to an intent-to-treat analysis.

RESULTS AND LIMITATIONS:

A total of 101 patients were evaluated. Median PFS was 7.9 mo in Arm A and 8.6 mo in Arm B (p=0.049) and the median duration of response was 8.5 and 19.2 mo, respectively (p=0.0013). Nine partial responses were observed in Arm A, and three complete and 14 partial responses were observed in Arm B (17.6% vs 34.0%; p=0.058); 24 and 21 patients (47% and 42%), respectively, achieved stable disease. The most common grade 3-4 toxicities were fatigue plus asthenia (28% vs 16%; p=0.32) and hand-foot skin reactions (20% vs 18%).

CONCLUSIONS:

Sorafenib plus frequent low-dose IFN showed good efficacy and tolerability. Further investigations should be warranted to identify a possible positioning of this intriguing regimen (6% complete response rate) in the treatment scenario of mRCC.

• Authors: Sergio Bracarda, Camillo Porta, Corrado Boni, Armando Santoro, Claudia Mucciarini, Antonio Pazzola, Enrico Cortesi, Donatello Gasparro, Roberto Labianca, Francesco Di Costanzo, Alfredo Falcone, Michela Cinquini, Claudia Caserta, Chiara Paglino, Verena De Angelis
• Journal: European urology (Eur Urol) Vol. 63 Issue 2 Pg. 254-61 (Feb 2013) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 22964169 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012. Published by Elsevier B.V.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Interferon alpha-2
• Interferon-alpha
• Phenylurea Compounds
• Recombinant Proteins
• Niacinamide
• Sorafenib

Topics

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (administration & dosage)
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Bone Neoplasms (drug therapy, secondary)
• Carcinoma, Renal Cell (drug therapy, secondary)
• Disease-Free Survival
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage)
• Kidney Neoplasms (pathology)
• Liver Neoplasms (drug therapy, secondary)
• Lung Neoplasms (drug therapy, secondary)
• Male
• Middle Aged
• Niacinamide (administration & dosage, analogs & derivatives)
• Phenylurea Compounds (administration & dosage)
• Prospective Studies
• Recombinant Proteins (administration & dosage)
• Sorafenib
• Treatment Outcome