- Davis, Ian, Long, A., Yip, Sonia, Espinoza, David, Thompson, John F., Kichenadasse, G., Harrison, M., Lowenthal, R. M., Pavlakis, N., Azad, Arman, Kannourakis, George, Steer, C., Goldstein, D., Shapiro, J., Harvie, R., Jovanovic, L., Hudson, Amanda, Nelson, Chris, Stockler, Martin, Martin, Andrew
- Authors: Davis, Ian , Long, A. , Yip, Sonia , Espinoza, David , Thompson, John F. , Kichenadasse, G. , Harrison, M. , Lowenthal, R. M. , Pavlakis, N. , Azad, Arman , Kannourakis, George , Steer, C. , Goldstein, D. , Shapiro, J. , Harvie, R. , Jovanovic, L. , Hudson, Amanda , Nelson, Chris , Stockler, Martin , Martin, Andrew
- Date: 2015
- Type: Text , Journal article
- Relation: Annals of Oncology Vol. 26, no. 6 (2015), p. 1118-1123
- Full Text: false
- Reviewed:
- Description: Background: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results: We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received >= 22 weeks of alternating therapy; 78% received >= 22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.
Precision medicine : an optimal approach to patient care in renal cell carcinoma
- Sharma, Revati, Kannourakis, George, Prithviraj, Prashanth, Ahmed, Nuzhat
- Authors: Sharma, Revati , Kannourakis, George , Prithviraj, Prashanth , Ahmed, Nuzhat
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Frontiers in Medicine Vol. 9, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Renal cell cancer (RCC) is a heterogeneous tumor that shows both intra- and inter-heterogeneity. Heterogeneity is displayed not only in different patients but also among RCC cells in the same tumor, which makes treatment difficult because of varying degrees of responses generated in RCC heterogeneous tumor cells even with targeted treatment. In that context, precision medicine (PM), in terms of individualized treatment catered for a specific patient or groups of patients, can shift the paradigm of treatment in the clinical management of RCC. Recent progress in the biochemical, molecular, and histological characteristics of RCC has thrown light on many deregulated pathways involved in the pathogenesis of RCC. As PM-based therapies are rapidly evolving and few are already in current clinical practice in oncology, one can expect that PM will expand its way toward the robust treatment of patients with RCC. This article provides a comprehensive background on recent strategies and breakthroughs of PM in oncology and provides an overview of the potential applicability of PM in RCC. The article also highlights the drawbacks of PM and provides a holistic approach that goes beyond the involvement of clinicians and encompasses appropriate legislative and administrative care imparted by the healthcare system and insurance providers. It is anticipated that combined efforts from all sectors involved will make PM accessible to RCC and other patients with cancer, making a tremendous positive leap on individualized treatment strategies. This will subsequently enhance the quality of life of patients. Copyright © 2022 Sharma, Kannourakis, Prithviraj and Ahmed.
- Authors: Sharma, Revati , Kannourakis, George , Prithviraj, Prashanth , Ahmed, Nuzhat
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Frontiers in Medicine Vol. 9, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Renal cell cancer (RCC) is a heterogeneous tumor that shows both intra- and inter-heterogeneity. Heterogeneity is displayed not only in different patients but also among RCC cells in the same tumor, which makes treatment difficult because of varying degrees of responses generated in RCC heterogeneous tumor cells even with targeted treatment. In that context, precision medicine (PM), in terms of individualized treatment catered for a specific patient or groups of patients, can shift the paradigm of treatment in the clinical management of RCC. Recent progress in the biochemical, molecular, and histological characteristics of RCC has thrown light on many deregulated pathways involved in the pathogenesis of RCC. As PM-based therapies are rapidly evolving and few are already in current clinical practice in oncology, one can expect that PM will expand its way toward the robust treatment of patients with RCC. This article provides a comprehensive background on recent strategies and breakthroughs of PM in oncology and provides an overview of the potential applicability of PM in RCC. The article also highlights the drawbacks of PM and provides a holistic approach that goes beyond the involvement of clinicians and encompasses appropriate legislative and administrative care imparted by the healthcare system and insurance providers. It is anticipated that combined efforts from all sectors involved will make PM accessible to RCC and other patients with cancer, making a tremendous positive leap on individualized treatment strategies. This will subsequently enhance the quality of life of patients. Copyright © 2022 Sharma, Kannourakis, Prithviraj and Ahmed.
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