Phase I trial of bevacizumab plus sunitinib in patients with metastatic renal cell carcinoma

Feldman, Darren R.; Ginsberg, Michelle S.; Baum, Michael; Flombaum, Carlos D.; Hassoun, Hani; Velasco, Susanne; Fischer, Pamela J.; Ishill, Nicole; Ronnen, Ellen A.; Motzer, Robert J.

doi:10.1200/jco.2008.26.15_suppl.5100

Cited by 48 publications

(41 citation statements)

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“…Treatment with sunitinib is also associated with a risk of hypertension, and for this reason, it has been suggested that home bloodpressure monitoring be used [13]. The toxicity profile observed in our case series was in accordance with that observed in a study of bevacizumab plus sunitinib in the first-line setting in patients with mRCC [14].…”

Section: Discussionsupporting

confidence: 77%

Salvage Therapy with Bevacizumab–Sunitinib Combination after Failure of Sunitinib Alone for Metastatic Renal Cell Carcinoma: A Case Series

et al. 2009

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Section: Discussionsupporting

confidence: 77%

Salvage Therapy with Bevacizumab–Sunitinib Combination after Failure of Sunitinib Alone for Metastatic Renal Cell Carcinoma: A Case Series

et al. 2009

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“…Data is available suggesting a benefit to combined treatment with targeted therapies. A phase I trial investigated the combination of bevacizumab and sunitinib [49]. Twenty-six patients with metastatic RCC were enrolled with 1 CR, and 12 PRs.…”

Section: Combined Targeted Therapiesmentioning

confidence: 99%

Treatment of metastatic renal cell carcinoma

Reeves

Liu

2009

Cancer Chemother Pharmacol

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PurposeTo review the treatment of metastatic renal cell carcinoma (RCC), including the use of new targeted therapies. MethodsA search of MEDLINE (1966 to August 2008 and American Society of Clinical Oncology Meeting abstracts (2005 to May 2008) was preformed using the search terms bevacizumab, everolimus, interferonalfa (IFN-α), interleukin-2 (IL-2), sorafenib, sunitinib, temsirolimus, and RCC. Articles most pertinent to the treatment of metastatic RCC are reviewed. ResultsThe treatment of metastatic RCC has undergone a paradigm shift over the past 5 years from biologic response modifiers to new targeted therapies. Historically, response rates for the biological response modifiers, aldesleukin (IL-2), and IFN-α were approximately 15%. Recently, three targeted agents, sorafenib, sunitinib, and temsirolimus have been approved for the treatment of RCC. Additionally, bevacizumab has been investigated and shown to increase progression free survival in RCC. IL-2 remains the only agent to induce complete, durable remissions; however, many patients are not eligible for this therapy. Newer agents (sorafenib, sunitinib, and temsirolimus) have shown to be superior to IFN-α or placebo and bevacizumab combined with IFN-α has shown activity when compared to IFN-α alone. Unlike IL-2, the greatest benefit obtained with targeted therapies is in achieving stable disease (SD). Despite their benefit, targeted therapies have never been compared with each other in clinical trials and choosing the most appropriate agent remains challenging. To date, the optimal sequence or combination of treatments has not been defined; however, everolimus has recently demonstrated activity in patients progressing on targeted therapy. ConclusionsIL-2 remains the most active regimen in inducing complete responses; however, its use is accompanied by substantial morbidity and is limited to those with a good performance status. Targeted therapies are also efficacious in the treatment of RCC, with the major benefit being induction of SD. Future research will better define the sequencing of therapies, as well as, explore the activity of novel combination regimens.

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“…The combination of sunitinib and bevacizumab was also explored in a phase I study but, while active, exhibited unacceptable toxicity at the doses tested. 16 …”

Section: Discussionmentioning

confidence: 99%

Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma

Fischer¹,

Patel²,

Carducci³

et al. 2008

JCO

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Purpose-Concurrent inhibition of multiple oncogenic signaling pathways might improve the efficacy of anticancer agents and abrogate resistance mechanisms. This phase I study evaluated temsirolimus in combination with sunitinib in patients with advanced RCC.Patients and Methods-Eligibility included advanced RCC and ≤ 2 previous systemic regimens. At the starting dose, temsirolimus 15 mg was administered by intravenous (I.V.) infusion once weekly, and sunitinib 25 mg was administered orally once daily for 4 weeks, followed by a 2-week rest period.Results-In the first cohort, dose-limiting toxicities (grade 3 treatment-related toxicities that lasted ≥ 7 days) were observed in 2 of 3 patients. One patient experienced grade 3 rash during week 3, which led to treatment discontinuation. A second patient had grade 3 thrombocytopenia (platelet count, 48,000/μL), cellulitis, and gout during week 3 and was hospitalized; platelets recovered to 109,000/μL 4 days after discontinuation of protocol therapy. A third patient experienced rash, asthenia, diarrhea, stomatitis, constipation, fever, and rectal hemorrhage, all of which were mild in severity. The study was terminated because of dose-limiting toxicity observed at low starting doses of both agents.Conclusion-Concomitant use of I.V. temsirolimus 15 mg weekly and oral sunitinib 25 mg daily (4 weeks on, 2 weeks off) is not recommended.

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Phase I trial of bevacizumab plus sunitinib in patients with metastatic renal cell carcinoma

Cited by 48 publications

References 0 publications

Salvage Therapy with Bevacizumab–Sunitinib Combination after Failure of Sunitinib Alone for Metastatic Renal Cell Carcinoma: A Case Series

Salvage Therapy with Bevacizumab–Sunitinib Combination after Failure of Sunitinib Alone for Metastatic Renal Cell Carcinoma: A Case Series

Treatment of metastatic renal cell carcinoma

Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma

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