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Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib.

Flaig TW, Costa LJ, Gustafson DL, Breaker K, Schultz MK, Crighton F, Kim FJ, Drabkin H - Br. J. Cancer (2010)

Bottom Line: Pre-clinical data indicate that the combined inhibition of both the epidermal growth factor receptor and mTOR results in enhanced anticancer activity.The most common adverse events were rash and diarrhoea.The combination of sirolimus and erlotinib for RCC failed to demonstrate an advantage over available single-agent therapy in the second-line setting.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver School of Medicine, Mail Stop 8117, 12801 East 17th Avenue Room 8117, Aurora, CO 80045, USA. Thomas.Flaig@UCDenver.edu

ABSTRACT

Background: The mammalian target of rapamycin (mTOR) is an important therapeutic target in the treatment of renal cell carcinoma (RCC). Pre-clinical data indicate that the combined inhibition of both the epidermal growth factor receptor and mTOR results in enhanced anticancer activity.

Methods: All patients had metastatic RCC with progression after treatment with sunitinib and/or sorafenib. Treatment consisted of erlotinib 150 mg orally once a day starting on day 1 and sirolimus 6 mg orally on day 8 followed by 2 mg daily, adjusted according to blood levels.

Results: A total of 25 patients were enrolled between July 2006 and March 2008. The median progression-free survival (PFS) was 12 weeks (95% CI 5.9-18.1) and median overall survival (OS) 40 weeks (95% CI 0-85.7). No confirmed complete or partial responses were observed, but stable disease >6 months was noted in 21.8% (95% CI 4.9-38.6) of patients. The most common adverse events were rash and diarrhoea. There was no correlation between erlotinib, OSI-420 (days 8 and 15) or sirolimus (days 15 and 29) blood levels and PFS or OS.

Conclusions: The combination of sirolimus and erlotinib for RCC failed to demonstrate an advantage over available single-agent therapy in the second-line setting.

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Related in: MedlinePlus

Kaplan–Meier estimate of the OS.
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fig2: Kaplan–Meier estimate of the OS.

Mentions: Two patients withdrew consent before first response assessment or obvious progression. These patients are assessed for toxicity but not for efficacy. The median PFS was 12 weeks (95% CI 5.9–18.1) as displayed in Figure 1. The median OS was 40 weeks (95% CI 0–85.7, Figure 2). There were no objective responses according to RECIST criteria; however, 13 patients had SD beyond 8 weeks (56.5%, 95% CI 36.3–76.8) and of these, 5 (21.8, 95% CI 4.9–38.6) had SD lasting longer than 6 months. One subject had SD lasting 80+ weeks and was still on therapy at the time of this report. An analysis of best response by RECIST criteria indicates that 7 of 25 patients had a reduction in their RECIST measurements from baseline, ranging from a 1.8 to 17.0% reduction.


Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib.

Flaig TW, Costa LJ, Gustafson DL, Breaker K, Schultz MK, Crighton F, Kim FJ, Drabkin H - Br. J. Cancer (2010)

Kaplan–Meier estimate of the OS.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966634&req=5

fig2: Kaplan–Meier estimate of the OS.
Mentions: Two patients withdrew consent before first response assessment or obvious progression. These patients are assessed for toxicity but not for efficacy. The median PFS was 12 weeks (95% CI 5.9–18.1) as displayed in Figure 1. The median OS was 40 weeks (95% CI 0–85.7, Figure 2). There were no objective responses according to RECIST criteria; however, 13 patients had SD beyond 8 weeks (56.5%, 95% CI 36.3–76.8) and of these, 5 (21.8, 95% CI 4.9–38.6) had SD lasting longer than 6 months. One subject had SD lasting 80+ weeks and was still on therapy at the time of this report. An analysis of best response by RECIST criteria indicates that 7 of 25 patients had a reduction in their RECIST measurements from baseline, ranging from a 1.8 to 17.0% reduction.

Bottom Line: Pre-clinical data indicate that the combined inhibition of both the epidermal growth factor receptor and mTOR results in enhanced anticancer activity.The most common adverse events were rash and diarrhoea.The combination of sirolimus and erlotinib for RCC failed to demonstrate an advantage over available single-agent therapy in the second-line setting.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver School of Medicine, Mail Stop 8117, 12801 East 17th Avenue Room 8117, Aurora, CO 80045, USA. Thomas.Flaig@UCDenver.edu

ABSTRACT

Background: The mammalian target of rapamycin (mTOR) is an important therapeutic target in the treatment of renal cell carcinoma (RCC). Pre-clinical data indicate that the combined inhibition of both the epidermal growth factor receptor and mTOR results in enhanced anticancer activity.

Methods: All patients had metastatic RCC with progression after treatment with sunitinib and/or sorafenib. Treatment consisted of erlotinib 150 mg orally once a day starting on day 1 and sirolimus 6 mg orally on day 8 followed by 2 mg daily, adjusted according to blood levels.

Results: A total of 25 patients were enrolled between July 2006 and March 2008. The median progression-free survival (PFS) was 12 weeks (95% CI 5.9-18.1) and median overall survival (OS) 40 weeks (95% CI 0-85.7). No confirmed complete or partial responses were observed, but stable disease >6 months was noted in 21.8% (95% CI 4.9-38.6) of patients. The most common adverse events were rash and diarrhoea. There was no correlation between erlotinib, OSI-420 (days 8 and 15) or sirolimus (days 15 and 29) blood levels and PFS or OS.

Conclusions: The combination of sirolimus and erlotinib for RCC failed to demonstrate an advantage over available single-agent therapy in the second-line setting.

Show MeSH
Related in: MedlinePlus