Renal cell carcinoma, treatment

Radiation therapy generally is considered to be the treatment of choice for most patients. Exceptions to this include patients with prior radiation to the treatment site and patients with inherently radioresistant tumors (e.g., melanoma and renal cell carcinoma). The radiation field should include two vertebral bodies above and below the involved area. 

USP received a medication error report involving the products Neumega (oprel-vekin) and Proleukin (aldesleukin). Oprelvekin, a recombinant human interleukin-11 product used to stimulate platelet production in selected patients undergoing chemotherapy, is sometimes abbreviated as IL-11. Aldesleukin, a recombinant human interleukin-2 derivative indicated in designated patient populations for the treatment of metastatic renal-cell carcinoma, is sometimes abbreviated as IL-2. 

Temsirolimus (35 ToriseF, CCI-779 Wyeth, 2007), a semi-synthetic derivative of sirolimus (34), is an intravenous drug for the treatment of renal cell carcinoma (RCC) ° developed by Wyeth Pharmaceuticals... 

Everolimus (40 Afinitor Novartis, 2009), a rapamycin analog, is the 42-0-(2-hydroxyethyl) derivative of sirolimus (34), and is marketed as an immunosuppressant by Novartis under the tradename Afinitor for use in advanced renal cell carcinoma.In March 2009, the FDA approved everolimus (40) for use against advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib. The drug works similarly to sirolimus as an inhibitor of mTOR (mammalian target of rapamycin), a serine-threonine kinase, downstream of the PI3K/AKT pathway. Everolimus (40) binds to an intracellular protein, EKBP-12, resulting in an inhibitory... 

Gore ME. (2007) Temsirolimus in the treatment of advanced renal cell carcinoma Ann Oncol 18(Suppl 9) ix87-ix88. 

Humanized and chimerized MAbs have been developed for the treatment of non-Hodgkin lymphoma, renal cell carcinoma, ovarian carcinoma, breast cancer, melanoma, and neuroblastoma [117,119,120,123,124]. Patients with relapsed or refractory myeloid leukaemias that have been treated with HuM95, did not develop significant HAMA responses [59]. 

The first IL to be approved for medical use was IL-2, approved in 1992 by the FDA for the treatment of renal cell carcinoma. Several additional IL preparations are currently in clinical trials (Table 5.2). 

Sorafenib is a kinase inhibitor with both antiproliferative and anti-angiogenic activity. Approved for the treatment of advanced renal cell carcinoma and for the treatment of patients with hepatocellular carcinoma. Peak plasma levels of sorafenib are generally observed 3 hours after oral administration. The... 

Carmustine and lomustine can produce remissions that last from 3 to 6 months in 40 to 50% of patients with primary brain tumors. Both drugs also are used as secondary treatment of Hodgkin s disease and in experimental combination chemotherapy for various types of lung cancer. Other tumors in which remission rates of 10 to 30% have been obtained are non-Hodgkin s lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and colorectal cancer. 

Interferon alfa-2b is useful in the treatment of a rare form of chronic leukemia, hairy cell leukemia, in which it produces remissions in 60 to 80% of patients. However, it has minimal antitumor activity in most human cancers. Remissions lasting a few months have been observed in 10 to 20% of patients with lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and ovarian carcinoma. 

Sorafenib is a diphenylurea multitargeted inhibitor of kinases (VEGFRs, C-Raf kinase, etc.). It has been registered for treatment of renal cell carcinoma. It is still undergoing Phase II evaluation for other indications. ... 

Unlabeled Uses Treatment of acquired immune deficiency syndrome (AlDS),AIDS-re-lated Kaposi s sarcoma, malignant melanoma, renal cell carcinoma... 

Quesada, J.R., L. Evans, S.R. Saks, and J.U. Gutterman, Recombinant interferon alpha and gamma in combination as treatment for metastatic renal cell carcinoma. J Biol Response Mod, 1988. 7(3) 234-9. 

H. Other considerations Interferon alfa-2a has been designated an orphan drug product for the treatment of chronic myelogenous leukemia, AIDS-related Kaposi s sarcoma, renal cell carcinoma, metastatic malignant melanoma, and esophageal and colorectal cancer. 

Indications Treatment of adults with metastatic renal cell carcinoma and adults with metastatic melanoma... 

B. Indications and nse Proleukin is indicated for the treatment of adults with metastatic renal cell carcinoma. Proleukin is also indicated for the treatment of adults with metastatic melanoma. Careful patient selection is mandatory prior to the administration of the cytokine. 

H. Other considerations Proleukin has been designated an orphan drug for use in the treatment of metastatic renal cell carcinoma, metastatic melanoma, non-Hodgkin s lymphoma, and primary immunodeficiency disease associated with T-cell defects. 

For the treatment of adults 18 years of age or older with metastatic renal cell carcinoma... 

Reeves, D. J., Liu, C. Y. (2009) Treatment of metastatic renal cell carcinoma. Cancer Chemother Pharmacol 64, 11-15. 

Proleukin is a recombinant human IL-2 that received approval for the treatment of renal cell carcinoma in 1992 and for the treatment of metastatic melanoma in 1998. It is also being evaluated for the treatment of non-Hodgkin s lymphoma (NHL). The therapy is restricted to patients with normal cardiac and pulmonary functions. 

Grande C, Firvida JL, Navas V, Casal J. 2006. Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma. Anticancer Drugs. 17 1-12. 

McDermott DF. 1007. Update on the application of interleukin 2 in the treatment of renal cell carcinoma. Clin Can Res. 13 716S-720S.. 

High-dose IL-2 is approved for the treatment of metastatic renal cell carcinoma. The tumor is intrinsically immunogenic, and can elicit a host immune response that infrequently results in spontaneous remission of disease administration of IL-2 is believed to augment the normal immune response [53]. In a Phase II study that supported the approval of high-dose IL-2 for this indication, 15% of patients achieved objective responses (8% were partial responses and 7% complete responses). In this trial, patients received IL-2 at 600 000 or 720 000 U/kg per dose. The cumulative dose and the efficacy were similar between dose groups patients receiving the higher dose tolerated fewer cycles of therapy due to toxicity. 

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