Safety and Efficacy of Sorafenib in Elderly Patients Treated in the North American Advanced Renal Cell Carcinoma Sorafenib Expanded Access Program

Bukowski, Ronald M.; Stadler, Walter M.; McDermott, David F.; Dutcher, Janice P.; Knox, Jennifer J.; Miller, Wilson H.; Hainsworth, John D.; Henderson, Charles A.; Hajdenberg, Julio; Kindwall‐Keller, Tamila L.; Ernstoff, Marc S.; Drabkin, Harry A.; Curti, Brendan D.; Chu, Luis; Ryan, Christopher W.; Hotte, Sébastien J.; Xia, Chenghua; Cupit, Lisa; Figlin, Robert A.

doi:10.1159/000320223

Cited by 41 publications

(19 citation statements)

References 37 publications

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“…In a population of advanced renal cell carcinoma patients aged ≥70 years, sorafenib was shown to be as safe and effective as in patients aged <70 years [23]. More recently, older populations with advanced HCC treated with sorafenib were compared with younger groups [24,25].…”

Section: Discussionmentioning

confidence: 99%

Sorafenib in Elderly Patients with Advanced Hepatocellular Carcinoma: A Case Series

Montella¹,

Addeo²,

Cennamo³

et al. 2013

Oncology

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Objective: The management of hepatocellular carcinoma (HCC) in elderly patients is significantly more complicated than in younger patients because of medical comorbidities, advanced status at diagnosis, reduced liver function and altered drug pharmacokinetics. Our objective was a revision of the charts of unselected elderly patients with HCC being treated with a reduced starting dose of sorafenib. Methods: Activity, adverse events and quality of life were evaluated during the treatment. Sixty patients (47 males and 13 females) aged more than 70 years old (range 70-90, median 76 years) were retrospectively reviewed. Results: One complete and one partial response were achieved in the series (overall response rate 3.3%). Stable disease accounted for 76.6% (46 out of 60 patients). The disease control rate (complete plus partial response plus stable disease) was 80%. Median time to progression (TTP) was 7.0 months (95% CI, 5.2-8.7 months) and median survival was 10.0 months (95% CI, 5.0-14.9 months). Thrombosis correlated to TTP. Full doses of sora-fenib were reached in 11 out of 60 patients (18.3%). The evaluation of quality of life did not show any significant change during the study. Conclusions: Sorafenib at a reduced dose can be safely used in elderly HCC patients with maintenance of activity and increased tolerability.

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Section: Discussionmentioning

confidence: 99%

Sorafenib in Elderly Patients with Advanced Hepatocellular Carcinoma: A Case Series

Montella¹,

Addeo²,

Cennamo³

et al. 2013

Oncology

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“…Rarely, it can also cause hematological abnormalities, including leukopenia, anemia, neutropenia and thrombocytopenia; and severe cardiovascular adverse event such as hypertensive crisis, myocardial ischemia and congestive heart failure. It has been reported that almost a third of the patients on a full dose of sorafenib (400 mg/BD) required a dose reduction and 10-17% of patients ceased treatment with the drug due to serious adverse events (8,13). Based on this, a combination treatment strategy with sorafenib and an agent that has synergistic effects is being evaluated.…”

Section: Discussionmentioning

confidence: 99%

Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft model of human renal cell carcinoma

Yuen

Sim

et al. 2012

International Journal of Oncology

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Abstract. Sorafenib, a multikinase inhibitor, is currently used as monotherapy for advanced renal cell carcinoma (RCC). However, adverse effects associated with its use have been experienced by some patients. In this study, we examined the antitumor and antiangiogenic activities of low-dose sorafenib in combination with the MEK inhibitor AZD6244 (sorafenib/ AZD6244) in a preclinical model of RCC. Primary RCC 08-0910 and RCC 786-0 cells as well as patient-derived RCC models were used to study the antitumor and antiangiogenic activities of sorafenib/AZD6244. Changes of biomarkers relevant to angiogenesis and cell cycle were determined by western immunoblotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry. Treatment of RCC 786-0 cells with sorafenib/AZD6244 resulted in G 1 cell cycle arrest and blockade of serum-induced cell migration. Sorafenib/AZD6244 induced apoptosis in primary RCC 08-0910 cells at low concentrations. In vivo addition of AZD6244 to sorafenib significantly augmented the antitumor activity of sorafenib and allowed dose reduction of sorafenib without compromising its antitumor activity. Sorafenib/AZD6244 potently inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-β and ERK, p90RSK, p70S6K, cdk-2 and retinoblastoma. Sorafenib/AZD6244 also caused upregulation of p27, Bad and Bim but downregulation of survivin and cyclin B1. These resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. Our findings showed that AZD6244 and sorafenib complement each other to inhibit tumor growth. This study provides sound evidence for the clinical investigation of low-dose sorafenib in combination with AZD6244 in patients with advanced RCC.

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“…15 Insights into the safety and activity of sorafenib in a larger population of patients with advanced RCC were gathered from 2 expanded access programs prior to regulatory approval of sorafenib (the North America [NA-] and European [EU-] Advanced Renal Cell Carcinoma Sorafenib [ARCCS] studies). [16][17][18] Although the inclusion criteria for patients enrolled in these expanded access programs were broader than those used for the TARGET study, some exclusion criteria meant that the studied populations were not fully representative of patients encountered in routine clinical practice settings. For example, patients with cardiac arrhythmias, active coronary artery disease or ischemia, or uncontrolled hypertension were excluded from the NA-ARCCS, and < 1% of patients had received prior TKI therapy.…”

Section: Introductionmentioning

confidence: 99%

Sorafenib Treatment of Advanced Renal Cell Carcinoma Patients in Daily Practice: The Large International PREDICT Study

Jäger

Mardiak

et al. 2015

Clinical Genitourinary Cancer

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This large, prospective, noninterventional study assessed the efficacy and safety of sorafenib in patients with advanced renal cell carcinoma (RCC) in a clinical practice setting. Sorafenib was generally well tolerated, with no unexpected adverse events observed, and provided clinical benefit in this diverse patient population. Background: Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies. Patients and Methods: PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib) was a prospective, noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries. Patient characteristics, therapy duration, tumor status, and tolerability were assessed at baseline and during routine follow-up. Results: Overall, 2599 patients were evaluable for safety and 2311 for efficacy. The diverse population included patients with brain metastases (5%), non-clear-cell histologies (17%), high Memorial Sloan-Kettering Cancer Center risk score (11%), poor Eastern Cooperative Oncology Group performance status (PS ! 2, 29%), and patients with no previous nephrectomy (16%) or no previous systemic therapy (37%). The median duration of sorafenib therapy was 7.3 months and was similar in clinically relevant subgroups (eg, patients with PS 2, brain metastases, or concomitant hypertension or diabetes [range, 6.7-7.0 months]). The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies (4.6 and 4.8 months, respectively). The most common drug-related adverse events were handefoot skin reaction (20%), diarrhea (17%), and rash (8%). Conclusion: Sorafenib was generally well tolerated and provided clinical benefit in a large, diverse population of patients with advanced RCC treated in routine clinical practice.

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Safety and Efficacy of Sorafenib in Elderly Patients Treated in the North American Advanced Renal Cell Carcinoma Sorafenib Expanded Access Program

Cited by 41 publications

References 37 publications

Sorafenib in Elderly Patients with Advanced Hepatocellular Carcinoma: A Case Series

Sorafenib in Elderly Patients with Advanced Hepatocellular Carcinoma: A Case Series

Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft model of human renal cell carcinoma

Sorafenib Treatment of Advanced Renal Cell Carcinoma Patients in Daily Practice: The Large International PREDICT Study

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