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After the approval of several drugs aimed at renal-cell-cancer treatment such as sorafenib, sunitinib, temsirolimus and bevacizumab plus interferon, sequential therapies have been added to the daily oncology practice.
An important cumulus of evidence suggests that sequential administration of these agents provides significant clinical benefits such as tumor-size reduction and progression-free-survival (PFS) extension; these are facts which have been proved in a large quantity of patients.
The administration of these agents in the appropriate order enables the increase of overall PFS in up to 27 months, which may increase overall survival of renal-cancer patients up to 40 months in a near future.
The following table suggests, according to the published studies, that an overall progression-free survival between 20 and 27 months can be obtained through the use of sequential therapies.
Table. Progression-free survival in patients under treatment with sequential therapies (*)
|
Sunitinib2 11 months |
Sorafenib 4,5 months |
Everolimus3 4 months |
|
19,5 |
|
Bevacizumab más interferón7 10,2 months |
Sorafenib1 6 months |
Sunitinib4 6,5 months |
Everolimus3 4 months |
27,1 |
|
Bevacizumab más interferón7 10,2 months |
Sunitinib5
7 months |
Sorafenib4 4,5 months |
Everolimus3 4 months |
25,7 |
|
Interferón2 5 months |
Axitinib8 15,7 months |
Everolimus15 4 months |
|
24,7 |
|
Bevacizumab más interferón7 10,2 months |
Sorafenib1 6 months |
Axitinib6 7,4 months |
Everolimus3 4 months |
27,6 |
1. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125-134.
2. Motzer R, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115-124.
3. Sablin MP, Bouaita L, Balleyguier C, et al. Sequential use of sorafenib and sunitinib in renal cancer: retrospective analysis in 90 patients [abstract]. J Clin Oncol. 2007;25(18 suppl):Pages. Abstract 5038.
4. Rini BI, Wilding GT, Hudes G, et al. Axitinib (AG-013736; AG) in patients (pts) with metastatic renal cell cancer (RCC) refractory to sorafenib [abstract]. J Clin Oncol. 2007;25(18 suppl):Pages. Abstract 5032.
5. Schwarzberg T, Regan MM, Liu V, et al. Retrospective analysis of interleukin-2 therapy in patients with metastatic renal cell carcinoma who had received prior antiangiogenic therapy [abstract]. J Clin Oncol. 2008;26 (20 suppl):Pages. Abstract 5044.
6. Rini BI, Michaelson MD, Rosenberg JE, et al. Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. J Clin Oncol. 2008;26:3743-3748.
7. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell
carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103-2111.
8. Rixe O, Bukowski RM, Michaelson MD, et al. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell
cancer: a phase II study. Lancet Oncol. 2007;8:975-984.
(*) Supposing data from the second-line therapies can be extrapolated to a third-line setting
Escudier B, Gross Goupil M, Massard C y col. Sequential Therapy in Renal CellCarcinoma. Cancer 2009;115(10 suppl):2321–6 |