A randomized, open label, multicenter phase II study of first line therapy with Sorafenib in association with Interleukin 2 versus Sorafenib alone in patients with unresectable and/or metastatic renal cell carcinoma (RCC)
Nel luglio 2006 é stato avviato uno studio sul carcinoma renale.
Lo studio (Protocollo 38/06) aveva l’obiettivo di verificare l’efficacia in termini di controllo della crescita tumorale della terapia di combinazione sorafenib ed interleuchina 2 rispetto ad una monoterapia con il solo sorafenib nel carcinoma a cellule renali in fase avanzata.
Sono stati arruolati 131 pazienti.
Centri partecipanti : Fondazione IRCCS Istituto Nazionale Tumori, MILANO
Az. Ospedaliera Carlo Poma, MANTOVA
Istituto IRCCS S. Raffaele, MILANO
Az. Ospedaliera S.Anna, COMO
Az Ospedaliera Universitaria Senese, SIENA
Az. Ospedaliera S.Maria della Misericordia, UDINE
Ospedale Fatebenefratelli, ROMA
Az. Ospedaliera Ospedali Riuniti, ANCONA
Spedali Civili, BRESCIA
Ospedale S.Gerardo, MONZA (MI)
Ospedale S. Chiara, PISA
Ospedale G. da Saliceto, PIACENZA
Ospedale S. Maria della Misericordia, PERUGIA
Presidio Ospedaliero di GORGONZOLA (MI)
Istituto Oncologico Veneto IRCCS, PADOVA
Istituto per la Ricerca e la Cura del Cancro IRCCS, CANDIOLO (TO)
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, FORLI’
Ospedale Civile di Sondrio, SONDRIO
Fondazione IRCCS Policlinico S. Matteo, PAVIA
Ospedali Riuniti di BERGAMO
- Sorafenib with interleukin-2 vs sorafenib alone in metastatic renal cell carcinoma: the ROSORC trial
(Procopio G, Verzoni E, Bracarda S, Ricci S, Sacco C, Ridolfi L, Porta C, Miceli R, Zilembo N, Bajetta E. on behalf of Italian Trials in Medical Oncology I.T.M.O. Group)
Br J Cancer. 2011 Apr 12;104(8):1256-61. doi: 10.1038/bjc.2011.103. Epub 2011 Mar 29 Abstract
Preclinical investigations support combining sorafenib with IL-2 in the treatment of metastatic renal cell carcinoma (mRCC).
In this open-label, phase II study, 128 patients with mRCC were randomised to receive oral sorafenib, 400 mg twice daily, plus subcutaneous IL-2, 4.5 million international units (MIU) five times per week for 6 in every 8 weeks, or sorafenib alone. After enrolment of the first 40 patients, IL-2 dose was reduced to improve the tolerability.
After a median follow-up of 27 months, median progression-free survival (PFS) was 33 weeks with sorafenib plus IL-2, and 30 weeks with sorafenib alone (P=0.109). For patients receiving the initial higher dose of IL-2, median PFS was 43 weeks vs 31 weeks for those receiving the lower dose. The most common adverse events were asthenia, hand-foot syndrome, hypertension, and diarrhoea. Grade 3-4 adverse events were reported for 38 and 25% of patients receiving combination and single-agent treatment, respectively.
The combination of sorafenib and IL-2 did not demonstrate improved efficacy vs sorafenib alone. Improvements in PFS appeared greater in patients receiving higher-dose IL-2.
PMID: 21448165 [PubMed – indexed for MEDLINE] PMCID: PMC3078589
Download articolo: Br J Cancer. 2011 Apr 12;104(8):1256-61
- Overall survival for sorafenib plus interleukin-2 compared with sorafenib alone in metastatic renal cell carcinoma (mRCC): final results of the ROSORC trial.
(Procopio G1, Verzoni E, Bracarda S, Ricci S, Sacco C, Ridolfi L, Porta C, Miceli R, Zilembo N, Bajetta Eon behalf of Italian Trials in Medical Oncology I.T.M.O. Group)
Ann Oncol. 2013 Dec;24(12):2967-71. doi: 10.1093/annonc/mdt375. Epub 2013 Sep 24. Abstract
The ROSORC trial, a randomised, phase II trial comparing sorafenib plus interleukin (IL-2) versus sorafenib alone as first-line treatment of metastatic renal cell carcinoma (mRCC) failed to demonstrate differences in progression-free survival (PFS). Updated overall survival (OS) results are reported.
PATIENTS AND METHODS:
In this study, 128 patients were randomised to receive sorafenib 400 mg twice daily plus subcutaneous IL-2 4.5 million international units (MIU) five times per week for 6 weeks every 8 weeks (arm A) or sorafenib alone (arm B). OS was estimated with the Kaplan-Meier method and compared with the two-sided log-rank test.
After a median follow-up of 58 months (interquartile range: 28-63 months), the median OS was 38 and 33 months in arms A and B, respectively (P = 0.667). The 5-year OS was 26.3% [95% confidence interval (CI) 15.9-43.5) and 23.1% (95% CI 13.2-40.5) for the combination- and single-agent arm, respectively. Most of the patients who were refractory to first-line treatment were subsequently treated with different targeted agents; they had a median survival greater than expected.
This outcome suggests a synergistic effect of the subsequent therapies following sorafenib failure.
CLINICAL TRIALS GOV IDENTIFIER:
first-line treatment; interleukin-2; renal cell carcinoma; sorafenib; targeted therapies
PMID: 24063860 [PubMed – indexed for MEDLINE]
Download articolo: Ann Oncol. 2013 Dec;24(12):2967-71