Article

Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group.

Oregon Health and Science University, Portland, OR, USA.
Journal of Clinical Oncology (impact factor: 18.37). 09/2007; 25(22):3296-301. DOI:10.1200/JCO.2007.11.1047 pp.3296-301
Source: PubMed

ABSTRACT This phase II study evaluated the activity of combined treatment with interferon alfa-2b and sorafenib, a Raf and multiple receptor tyrosine kinase inhibitor, in patients with advanced renal carcinoma.
Eligible patients had metastatic or unresectable renal carcinoma with a clear-cell component, no prior systemic therapy, performance status 0 to 1, and measurable disease. Treatment consisted of interferon alfa-2b 10 x 10(6) U subcutaneously three times weekly and sorafenib 400 mg orally bid. The primary end point was confirmed Response Evaluation Criteria in Solid Tumors response rate.
Twelve (19%) of 62 assessable patients achieved an objective confirmed response. An additional 31 (50%) had an unconfirmed partial response or stable disease as best response. The median progression-free survival was 7 months (95% CI, 4 to 11 months). The most common adverse events were fatigue, anorexia, anemia, diarrhea, nausea, rigors/chills, leukopenia, fever, and transaminase elevation. Von Hippel-Lindau gene mutations were detected in four (22%) of 18 archival tumor specimens.
The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone. The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen.

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    Article: Pharmacokinetic results of a phase I trial of sorafenib in combination with dacarbazine in patients with advanced solid tumors.
    Erich Brendel, Matthias Ludwig, Chetan Lathia, Caroline Robert, Stanislas Ropert, Jean-Charles Soria, Jean-Pierre Armand
    [show abstract] [hide abstract]
    ABSTRACT: Sorafenib, a multikinase inhibitor of Raf and several growth factor receptors, is under investigation in combination with dacarbazine, a commonly used chemotherapeutic agent for the treatment of many cancers. The current phase I study investigates the effects of sorafenib on the pharmacokinetic (PK) profile of dacarbazine and its metabolite 5-amino-imidazole-4-carboxamide (AIC). (AIC is formed in amounts equimolar to the active alkylating moiety, methane diazohydroxide, which is undetectable by known validated assays.) Patients with advanced solid tumors received intravenous dacarbazine 1,000 mg/m(2) on day 1 of a 21-day cycle to evaluate the PK of dacarbazine alone. Sorafenib 400 mg was administered twice daily continuously starting at day 2 of cycle 1. The PK of dacarbazine in the presence of sorafenib was assessed on day 1 of cycle 2. Sorafenib PK was also assessed at steady state. PK data were available for 15 of 23 patients. With concomitant administration of sorafenib, the mean AUC and C (max) values of dacarbazine were reduced by 23 and 16%, respectively. Mean AUC and C (max) values of AIC were increased by 41 and 45%, respectively, with individual increases of up to 106 and 136%, respectively. The apparent terminal half-lives of the two compounds were not significantly influenced by sorafenib. Based on coefficients of variation, the AUC and C (max) values for sorafenib and its three metabolites were highly variable with dacarbazine coadministration. Concomitant administration of sorafenib and dacarbazine as described above may result in decreased dacarbazine exposure but increased AIC exposure.
    Cancer Chemotherapy and Pharmacology 07/2011; 68(1):53-61. · 2.83 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

11 months
 
18 archival tumor specimens
 
62 assessable patients
 
adverse events common
 
anemia
 
anorexia
 
common adverse events
 
diarrhea
 
leukopenia
 
multiple receptor tyrosine kinase inhibitor
 
nausea
 
phase II study
 
prior systemic therapy
 
Raf
 
renal carcinoma
 
Solid Tumors response rate
 
sorafenib 400 mg orally bid
 
transaminase elevation
 
unconfirmed partial response
 
unresectable renal carcinoma