Renal cell cancer treatment

Sorafenib is a multikinase inhibitor that inhibits both intracellular and extracellular kinases to decrease renal cell cancer proliferation. The half-life of sorafenib is 25 to 48 hours, with a bioavailability of 38% to 49% and a time to peak concentration of 3 hours. Sorafenib is metabolized primarily by the liver by CYP450 3A4. Sorafenib is used for the treatment of renal cell cancer. The primary side effects of sorafenib include rash, hand-foot skin reaction, diarrhea, pruritus, and elevations in serum lipase. 

Proleukin is a recombinant form of IL-2. It is approved for the treatment of malignant melanoma and renal cell cancer. Ontak (denileukin diftitox) is a fusion protein for the treatment of persistent or recurrent T-cell lymphoma. Activated T cells express lL-2 receptors. Ontak has a fragment that binds to the IL-2 receptor while the other part presents a diphtheria toxin to kill the activated T cell. 

Aldesleukin is a recombinant form of human Interleukin-2 (IL-2). It has been approved for the treatment of malignant melanoma and renal cell cancer. The medicine is administered every 8 hours by a 15-minute intravenous infusion for a maximum of 14 doses. Adverse reactions include hypo- and hypertension, gastrointestinal disturbances, fever, fatigue, lethargy, joint pain, headache. Cardiovascular problems may occur. 

It is used for the treatment of non small cell lung carcinoma, breast carcinoma, Hodgkin s disease, ovarian carcinoma, squamous cell carcinoma of the head and neck, cervical squamous cell carcinoma, renal cell cancer and Kaposi s sarcoma. 

D.R. Parkinson, C.A. Seipp, J.H. Ein-horn, and D.E. White. 1994. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271 907-913. 

Risk factors for renal dysfunction have been analysed in 72 patients with metastatic renal cell cancer treated with high-dose aldesleukin (18 MU/m /day), interferon alfa (5 MU/m /day), and lymphokine-activated killer lymphocytes (94). There was some tjrpe of renal dysfunction in 97%, of whom 69% developed renal toxicity of grade 2 (creatinine 260-525 pmol/l) or grade 3 (creatinine 525-1050 pmol/l). Although renal function commonly resolved between successive treatment courses, six patients had a persistently raised creatinine concentration (more than 20% above baseline). Among the various potential risk factors, a multivariate analysis showed that the significant risk factors for severe renal dysfunction were male sex, pre-treatment hjrpertension, and sepsis during treatment. 

Vlasveld LT, van de Wiel-van Kemenade E, de Boer AJ, Sein JJ, Gallee MP, Krediet RT, Mellief CJ, Rankin EM, Hekman A, Figdor CG. Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer. Cancer Immunol Immunother 1993 36(3) 210-13. 

Bortolussi R, Fabiani F, Savron F, Testa V, Lazzarini R, Sorio R, De Conno F, Caraceni A. Acute morphine intoxication during high-dose recombinant interleukin-2 treatment for metastatic renal cell cancer. Eur J Cancer 1994 30A(12) 1905-7. 

Vinblastine is used in combination with other cytotoxic agents for the treatment of disseminated Hodgkin s disease stages III and IV, non-Hodgkin s lymphoma, histiocytic lymphoma, and advanced carcinoma of the testis. It has also been used for the treatment of bladder cancer, melanoma, and renal cell cancer. The usual adult dosage is 3-6 mg/m intravenously for the treatment of testicular germ cell tumors and Hodgkin s disease (1,2). 

Since interleukin-2 induced rate of response in patients with metastatic melanoma or renal cell cancer is schedule and dose dependent, and because renal toxicity is the main cause of treatment discontinuation, more studies are warranted to elucidate the observed nephrotoxicity. 

Morroquin etal. [12] studied the effect of high-dose IL-2 therapy in the treatment of patients with metastatic melanoma and renal cell cancer. They fotmd that there... 

Morroquin et al. [44] studied the effect of high-dose IL-2 therapy in the treatment of patients with metastatic melanoma and renal cell cancer. Animal models have shown that successful treatment with IL-2 is dose and schedule dependent. They found that there was a subset of patients who could not tolerate high doses or retreatment due to renal toxicity. Pretreatment factors that were significantly associated with renal toxicity were male sex, diagnosis of renal cancer, previous nephrectomy, and older age. These patients also had higher baseline creatinine. 

Rebeccamycin is a natural product that inhibits DNA topoisomerase I and has been studied as a potential anticancer agent because of the importance of DNA topoisomerase I in cell growth and proliferation. Rebeccamycin analogues are being used in clinical trials for the treatment of neoplastic tumors,renal cell cancer, and leukemia, " rehO is one of the 11 genes in the rebeccamycin biosynthetic cluster. The protein product, RebO, is an L-amino acid oxidase that contains a noncovalently bound FAD. RebO catalyzes the oxidation of 7-chloro-L-tryptophan in an early step in rebeccamycin biosynthesis (Equation (4)). 

P-glycoprotein expression may occur in tumour types derived from tissues that normally express the protein, like renal cell cancer, but its overexpression may also be induced by the treatment with anticancer drugs. All Vinca alkaloids used in cancer therapy can induce the expression of P-glycoprotein and the associated multidrug resistance phenotype, due to the capacity of P-glycoprotein to pump out of the cell a... 

Reproducible antitumor activity has been reported in advanced MM and renal cell cancer, where response rates (partial and complete) are seen in 20-30% of patients. Complete responses, seen in 5-10% of patients, appear to be durable, with some patients free of disease beyond 5 years. IL-2 is being studied in the treatment of AML where it is capable of inducing remission in relapsed patients. Given following bone marrow transplantation, it appears that IL-2 can lengthen the remission duration compared to historical controls. 

Treatment of diabetes mellitus Leukemia, AIDS, and renal cell carcinoma AIDS, multiple sclerosis, and cancer Anemia and chronic renal failure Cancer treatment Heart attack... 

Several anticancer drugs are indoles, the most famous of which are the Catharanthus roseus plant alkaloids vinblastine (124) and vincristine (125) (Scheme 18), both of which continue to be important drugs for the treatment of Hodgkin s disease, childhood leukemia, and other cancers [141-143], The rebeccamycin analogue NSC-655649 (126) is in phase n trials for the treatment of metastatic renal cell cancer... 

The cytokine interleukin 2 (IL-2) is necessary for T cell growth, proliferation, and differentiation. An FDA-approved recombinant human IL-2 is used clinically as Proleukin (Prometheus Laboratories) for the treatment of metastatic melanoma and renal cell carcinoma. Erythema during IL-2 immunotherapy is common and was well described in a French study nearly 20 years ago with a report on generalized erythema followed by desquamation in 12 patients treated with the cytokine for renal cancer. Urticaria in eight renal cell cancer patients after the end of IL-2 therapy has also been reported. Skin tests with IL-2 on... 

Uses Bevacizumab, in combination with fiuoropyrimidine-based chemotherapy, is indicated for patients with metastatic carcinoma of the colon or rectum [155, 156 ", 157, 158 ] in combination with paclitaxel or docetaxel for first-line treatment of patients with metastatic breast cancer [159, 160 ] in addition to platinum-based chemotherapy, for first-line treatment of patients with unresectable, advanced, metastatic or recurrent non-small cell lung cancer, other than with predominantly squamous cell histology [161, 162 ] and in combination with interferon alfa-2a, for first-line treatment of patients with advanced and/or metastatic renal cell cancer [163, 164. ... 

Treatment concepts for liver metastases are determined by the biology of tbe disease and, in the case of the disease being confined to the liver, by the number and topographic location of the metastases. Colorectal liver metastases are the most frequent indication for the use of regional treatment concepts for the liver. Liver metastases from other primary tumors, such as the breast, neuroendocrine tumors (carcinoids), ocular melanoma, renal cell cancer, and sarcoma, have also been removed by treatment approaches confined to the liver with curative intent. 

In the meantime, at the University of Michigan and collaborating institutions, we have initiated nine phase II studies of TM treatment in specific cancers. For the most part these involve therapies of advanced disease, some using TM in combination with other agents, some using TM as sole therapy. One paper has been published, on renal cell cancer, with only modest potentially positive results (56), It is too early to report on the others, but results in some seem to be encouraging. 

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

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]. 

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. 

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