Cancer Treatment Today » Renal Cell Carcinoma

Xeloda for renal cell carcinoma – pro

M Levin, MD — Thu, 13 Sep 2012 16:08:09 +0000

Capecitabine is a novel fluoropyrimidine carbamate, orally administered and selectively activated to fluorouracil by a sequential triple enzyme pathway in liver and tumor cells.Oral capecitabine may be an active drug for the treatment of advanced renal cell carcinoma and is being evaluated in first- and second-line treatment schedules as monotherapy as well as in combination with immunotherapy agents.
In preclinical studies, renal cell tumors demonstrated high TP activity, suggesting that TP-activated capecitabine may be effective in this setting. In a pilot phase II study, capecitabine (1,250 mg/m2 twice daily for 14 days followed by a 7-day rest period) was administered to 22 patients with metastatic renal cell cancer that had progressed during or following immunotherapy. Among 12 patients for whom efficacy and toxicity data have been reported, one patient achieved a partial response, and disease was stabilized in all but one of the remaining patients (83%). There were no grade 4 adverse events and the only grade 3 adverse event was hand-foot syndrome, which occurred in two patients and resolved without capecitabine dose modification. Another phase II study has investigated capecitabine (1,000 mg/m2 twice daily on days 1-5 of weeks 5-8) in combination with immunotherapy (interleukin 2, interferon-, and oral 13-cis-retinoic acid) in 30 patients with metastatic renal cell carcinoma. This regimen, repeated for up to three cycles, produced an objective response rate of 34%, including two complete responses. A further 12 patients (40%) achieved disease stabilization. No grade 4 adverse events were observed, and grade 3 events were reported in only two patients (malaise and malaise, nausea/vomiting). There are published trials in combination with interferon, docetaxel and thalidomide.

*Amato RJ, Khan M. A phase I clinical trial of low-dose interferon-alpha-2A, thalidomide plus gemcitabine and capecitabine for patients with progressive metastatic renal cell carcinoma. Cancer Chemother Pharmacol. 2008 May;61(6):1069-73. Epub 2007 Aug 14.
*Amato RJ, Rawat A.
Interferon-alpha plus capecitabine and thalidomide in patients with metastatic renal cell carcinoma: a pilot study. Invest New Drugs. 2007 May;24(3):171-5
*Amato RJ. Thalidomide therapy for renal cell carcinoma. Crit Rev Oncol Hematol. 2003 Jun 27;46 Suppl:S59-65

Catharina Wenzel et al,Oral Chemotherapy with Capecitabine (Xeloda) in the Treatment of Metastatic Renal Cancer Failing Immunotherapy. Proc Am Soc Clin Oncol 19: 2000 (abstr 1457)
Wenzel C, Schmidinger MP, Locker GJ et al. Oral chemotherapy with capecitabine (Xeloda) in the treatment of metastatic renal cancer failing immunotherapy. Proc Am Soc Clin Oncol 2000;19:368a.
Övermann K, Buer J, Hoffman R et al. Capecitabine in the treatment of metastatic renal cell carcinoma. Br J Cancer 2000;83:583–587

Amato RJ, Mohammad T. Interferon-alpha plus capecitabine and thalidomide in patients with metastatic renal cell cancer. J Exp Ther Oncol. 2008;7(1):41-7

Torisel and Avastin for renal cell carcinoma – pro

M Levin, MD — Thu, 13 Sep 2012 16:06:54 +0000

Combination of Avastin and Temsirollimus for solid tumors is in a trial in renal cell carcinoma, NCT00619268. The TORAVA trial is designed to evaluate the progression-free rate at 48 weeks of a combination of Torisel® and Avastin® given at first-line treatment in patients with metastatic renal cancer. In addition, Wyeth Pharmaceuticals, in May, 2008 announced the initiation of the INTORACT (INvestigation of TORISEL and Avastin Combination Therapy) study, a worldwide randomized, open-label, phase 3b study comparing TORISEL® (temsirolimus) plus Avastin® (bevacizumab) versus Avastin plus interferon-alfa for first-line treatment of patients with advanced renal cell carcinoma (RCC). Wyeth Research is conducting the INTORACT study with the support and assistance of Roche and Genentech.

Both Torisel and Avastin are effective for renal cell carcinoma. Torisel is FDA approved as a single agent. Avastin is also an effective treatment for renal cell carcinoma.

Several studies indicate that Avastin is effective for renal cell carcinoma. A randomized, double-blind, Phase II trial was conducted comparing placebo with bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks in 166 patients with renal cancer, with significant positive results for Avastin. According to updated results from a phase II clinical trial presented at the 23rd annual Chemotherapy Foundation Symposium, treatment with the combination of Tarceva® (erlotinib) and Avastin® (bevacizumab) resulted in good survival among patients with metastatic renal cell carcinoma. Current NCCN guidelines recommend Avastin as an option for crossover therapy of renal cell carcinoma after first line therapy with IL2, sorafenib or sunitinib.

The combination of the two drugs, however, is not proven becauseit does not have scientific evidence the permits conclusions ot its effect on health outcomes and the above noted trials are ongoing.

Coppin C, Porzsolt F, Awa A, et al. Immunotherapy for advanced renal cell cancer. Cochrane Database Systematic Rev. 2004;3:CD001425.

Hainsworth J, Spigel D, Greco A. Combination Therapy with Bevacizumab and Erlotinib for Patients with Metastatic Clear Cell Renal Carcinoma. Proceedings from the 23rd annual Chemotherapy Foundation Symposium. New York. 2005; Abstract #22.

Aimery de Gramonta, Eric Van Cutsemb, Investigating the Potential of Bevacizumab in Other Indications: Metastatic Renal Cell, Non-Small Cell Lung, Pancreatic and Breast Cancer, Oncology Suppl. 3, 2005

Followup for renal cell carcinoma – pro

M Levin, MD — Fri, 07 Sep 2012 19:36:59 +0000

The guidelines recommend CT for routine followup of renal cel carcinoma patients on active treatment. Some guidelines recommend PET as well as an alternative or to supplement CT; however, CT remains the standard imaging modality for restaging.
In regard to PET/CT, little reliable information exists. There is currently limited experience with FDG-PET and renal cell carcinoma. One of the first studies evaluating 29 patients with solid renal masses demonstrated a sensitivity of 77% (20 of 26 patients with renal cancer)and 3 false positives (angiomyolipoma, pericytoma and pheochromocytoma). In another 3 patients, FDG-PET detected regional nodal metastases.
A second study evaluating factors in the degree of FDG uptake in renal cell carcinoma (n = 11) demonstrated that patients with higher grade tumors had positive FDG-PET studies. The fact that many renal cell carcinomas are lower in grade may explain the relatively low sensitivity.

Another limitation with FDG-PET evaluation of renal cell carcinoma is the fact that FDG is excreted by the kidneys. Thus, variable degrees of increased uptake are normally seen in the renal parenchyma and collecting system, making detection of focal increased uptake in a tumor difficult. PET scanning has been shown to be potentially useful in differentiating benign from malignant hepatic lesions, but limitations include false-positive and false-negative results. Its sensitivity for detecting metastatic lesions is better than for determining the presence of cancer in the renal primary site.

NCCN recommends chest and abdominal CT 4- 6 months, then as indicated. A recent guideline states: “FDG PET, whole body may have a role when CT and/or bone scan findings are equivocal.” ACR recommends: ”

For T1 tumors. As the risk of metastases is low, most surveillance protocols recommend that history, physical examination, laboratory tests, and a chest radiograph be obtained every 6 to 12 months for 3 years and then yearly until year 5. Others have suggested no imaging if the tumor is <2.5 cm. Most protocols do not recommend surveillance with abdominal computed tomography (CT) for patients with T1 tumors.
For T2 primary tumors. Most protocols recommend that history, physical examination, laboratory tests and a chest radiograph be obtained annually or every 6 months for 3 years, then annually thereafter till year 5. Protocols vary widely regarding the use of abdominal CT. Some do not recommend CT at all, while others recommend CT at year 2 and year 5. Still others recommend a CT every other year, or annually for 3 years following surgical removal, then annually thereafter.
For T3 or T4 primary tumors. Most protocols recommend that history, physical examination, laboratory tests, and a chest radiograph be obtained every 6 months for a few years, then annually thereafter. The vast majority of protocols recommend abdominal CT, with most recommending more frequent (every 3 to 6 months) CT imaging for 3 years after surgery and less frequently (yearly or every other year) thereafter. “

D. Soulières, MD MSc, Review of guidelines on the treatment of metastatic renal cell carcinoma
Curr Oncol. 2009 May; 16(Supplement 1): S67–S70.

Urological Tumours National Working Group. Renal cell carcinoma. Utrecht, The Netherlands: Association of Comprehensive Cancer Centres (ACCC); 2006 Oct 23. 108 p. [442 references]
Casalino DD, Francis IR, Baumgarten DA, Bluth EI, Bush WH Jr, Curry NS, Israel GM, Jafri SZ, Kawashima A, Papanicolaou N, Remer EM, Sandler CM, Spring DB, Fulgham P, Expert Panel on Urologic Imaging. Follow-up of renal cell carcinoma. [online publication]. Reston (VA): American College of Radiology (ACR); 2007. 5 p. [60 references]

Delbeke D, Martin WH, Sandler MP, Chapman WC, Wright JK Jr, Pinson CW. Evaluation of benign vs malignant hepatic lesions with positron emission tomography. Arch Surg. 1998;133:510-515.

Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115-124.

Dilhuydy MS, Durieux A, Pariente A, de Clermont H, Pasticier G, Monteil J, Ravaud A.. PET scans for decision-making in metastatic renal cell carcinoma: a single-institution evaluation.Oncology. 2006;70(5):339-44

Ak I, Can C..F-18 FDG PET in detecting renal cell carcinoma.Acta Radiol. 2005 Dec;46(8):895-9

clinical practice guidelines: B. Escudier, V. Kataja, and On behalf of the ESMO Guidelines Working GroupRenal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol (2010) 21(suppl 5): v137-v139

Casalino DD, Francis IR, Arellano RS, Baumgarten DA, Curry NS, Dighe M, Fulgham P, Israel GM, Leyendecker JR, Papanicolaou N, Prasad S, Ramchandani P, Remer EM, Sheth S, Expert Panel on Urologic Imaging. ACR Appropriateness Criteria® follow-up of renal cell carcinoma. [online publication]. Reston (VA): American College of Radiology (ACR); 2009. 6 p. [62 references]

UPTODATE, 2019
Surveillance for metastatic disease after definitive treatment for renal cell carcinoma
Authors:Brian Shuch, MDAllan J Pantuck, MD, MS, FACSIzak Faiena, MDSection Editor:Jerome P Richie, MD, FACSDeputy Editor:Sadhna R Vora, MD

Revlimid for renal cell carcinoma – pro

M Levin, MD — Thu, 06 Sep 2012 18:26:55 +0000

Thalidomide is an agent with complex antiangiogenic and immunomodulatory properties. It has been demonstrated to reduce mRNA and protein expression of bFGF and VEGF with resulting inhibitory effects on endothelial cell proliferation. Several small studies of thalidomide as a single agent in RCC have reported no complete responses, partial responses ranging from 0-17%, and stable disease in 17-64% of patients. In these studies, thalidomide was generally started at a low dose of 100-200 mg per day, and further escalated to higher doses until toxicity was achieved. When thalidomide analog, lenalidomide became available, it was studied in renal cell carcinoma as well.

Thalidomide has minimal activity. In a recent metastatic study(Margulis et al), single-agent thalidomide was inactive, and that the risk-benefit ratio clearly did not favor the use of thalidomide In small randomized, controlled 2009 trial (Jonasch et al), adjuvant thalidomide therapy after complete resection of high-risk RCC did not improve the 2- and 3-year RFS rates or cancer-specific death rates.

Lee CP, Patel PM, Selby PJ, Hancock BW, Mak I, Pyle L, James MG, Beirne DA, Steeds

Randomized phase II study comparing thalidomide with medroxyprogesterone acetate in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006 Feb 20;24(6):898-903.

Choueiri TK, Dreicer R, Rini BI, Elson P, Garcia JA, Thakkar SG, Baz RC, Mekhail TM, Jinks HA, Bukowski RM. Phase II study of lenalidomide in patients with metastatic renal cell carcinoma. Cancer. 2006 Dec 1; 107 (11): 2609-16.

Motzer, Robert J., Berg, William, Ginsberg, Michelle, Russo, Paul, Vuky, Jacqueline, Yu, Richard, Bacik, Jennifer, Mazumdar, Madhu Phase II Trial of Thalidomide for Patients With Advanced Renal Cell Carcinoma J Clin Oncol 2002 20: 302-306

Novik Y, Dutcher JP, Larkin M, Wiernik PH. Phase II Study of Thalidomide (T) in Advanced Refractory Metastatic Renal Cell Cancer (MRCC): a Single Institution Experience. Proc Am Soc Clin Oncol 2001; 20 (abstr 1057).

Margulis V, Matin SF, Tannir N, Tamboli P, Shen Y, Lozano M, Swanson DA, Jonasch E, Wood CG. Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma. Urology. 2009 Feb;73(2):337-41

NCCN, renal cell carcinoma

Revised 8/24/2011

Gemzar for renal cell carcinoma – pro

M Levin, MD — Wed, 05 Sep 2012 16:03:44 +0000

Lay Summary: Gemcitabine does not appear to be very active by itself in kidney cancer but may turn out to be effective in combinations.

Gemcitabine has some dated phase II evidence in a phase II trial and the response rates were quite low. There are moore recent studies in combination with other drugs. Researchers from Italy recently conducted a small clinical trial evaluating the combination of Gemzar® , alfa interferon and Proleukin® in 16 patients with metastatic renal cell cancer. Continued therapy with alfa interferon and Proleukin® was given to patients who responded or were stabilized by treatment. One patient achieved a complete disappearance of detectable cancer (complete remission) and 3 patients (28%) achieved at least a 50% reduction in their cancer (partial remission). In addition, 7 patients had their cancer stabilized by treatment. The average time to progression of cancer was approximately 14 months and the average survival was approximately 20 months. Treatment was generally well tolerated.

These researchers concluded that although this was a small clinical trial, it appears that the addition of Gemzar® to alfa interferon and Proleukin® may augment anti-cancer activity in metastatic renal cell cancer. Future clinical trials that involve larger numbers of patients and directly compare the addition of Gemzar® to alfa interferon and Proleukin®, compared to alfa interferon and Proleukin® alone are warranted.

Lilleby W, Fossa SD. Chemotherapy in metastatic renal cell cancer.World J Urol. 2005 Feb 22;

DeMulder PH, Weissbach L, Jakse G, et al: Gemcitabine: A phase II study in patients with advanced renal cancer. Cancer Chemother Pharmacol 37:491-495, 1996

Neri B, Doni L, Gemelli M, et al. Phase II trial of weekly intravenous gemcitabine administration with interferon and interleukin-2 immunotherapy for metastatic renal cell cancer. The Journal of Urology. 2002;168:956-958.

Chemotherapy for renal cell carcinoma – pro

M Levin, MD — Wed, 05 Sep 2012 03:52:13 +0000

Lay Summary: Chemotherapy is not effective for renal cell carcinoma, although sarcomatoid variants may fare better with chemotherapy.

Chemotherapy in treating renal cell has had a poor record, even though cytotoxic drugs are the cornerstone of therapy for most solid malignancies. Sarcomatoid variants may respond better to chemotherapy but the evidence for this is scant. A comprehensive review of 83 trials involving more than 4,000 patients reported a chemotherapy response rate of 6%.

Historically, patients have shown some response to therapy with the single agents floxuridine, 5-fluorouracil, and vinblastine. Floxuridine and 5-fluorouracil are antimetabolites that work by inhibiting thymidylate synthase, a pivotal enzyme that catalyzes the de novo production of thymidylate and thymidine nucleotides that are necessary for DNA synthesis. Vinblastine binds to tubulin, causing inhibition of the mitosis phase of the cell cycle. A comprehensive review reported overall response rates of 43% or lower in patients receiving floxuridine, an overall response rate of 10% in patients taking 5-fluorouracil, and overall response rates of 7% or lower in patients receiving vinblastine.

More recently, single-agent therapy with capecitabine or gemcitabine has shown some benefit when used in patients with metastatic disease. A phase II study evaluating the use of capecitabine in 26 patients in whom first- or second-line therapy with immunotherapy had failed found that 8.7% of patients exhibited a partial response.13 Another phase II trial evaluating the use of gemcitabine in 37 patients with metastatic or inoperable renal cell carcinoma yielded a response rate of 8.1%.

Multiple studies have been done evaluating combination chemotherapy regimens for advanced-stage renal cell carcinoma. Clinical trials evaluating the safety and efficacy of combinations using 5-fluoropyrimidines and gemcitabine are currently under way. Two recent trials using different combinations of capecitabine and gemcitabine have reported a partial response rate of 15%, with 53% of patients having stable disease.15,16 Another trial using a combination of gemcitabine and 5-fluorouracil has demonstrated a partial response rate of 17%. However, until more information is available, combination chemotherapy for metastatic renal cell carcinoma remains investigational.

The chemoresistance exhibited by renal cell carcinoma is unexplained, and consequently, unlike other solid tumor treatments, chemotherapy is not commonly pursued as treatment for advanced kidney cancer. The NCCN guidelines recommend single-agent chemotherapy as an option for first-line treatment of metastatic renal cell carcinoma in patients with non–clear cell histology.

Lilleby W, Fossa SD. Chemotherapy in metastatic renal cell cancer.World J Urol. 2005 Feb 22

Amato RJ. Chemotherapy for renal cell carcinoma. Semin Oncol. 2000;27:177-186.

nccn.org, Kidney cancer

Sarcomatoid variant of renal cell carcinoma and chemotherapy – pro

M Levin, MD — Tue, 04 Sep 2012 16:52:41 +0000

Chemotherapy is not generally considered appropriate for renal cell carcinoma (RCC), for which a variety of non-chemo agents have been FDA approved. However, the Sarcomatoid RCC has a worse prognosis than clear cell even when apparently localized, and many patients relapse after a nephrectomy. This entity is characterized by a high incidence of bone metastasis at presentation (48%) and by a tendency toward pathologic bone fractures.

There is an impression based on case reports and series that this subtype responds better to chemotherapy than RCC. Unfortunately, no prospective studies that corroborate it have been performed.

Paclitaxel/ carboplatin regimen is recently reported in several phase II studies and has not been very active. A 2009 study enrolled seventeen patients, of which 16 patients had papillary and 1 had collecting duct histology. The patient with collecting duct histology had a complete response, but no responses were observed in patients with papillary histology and the trial was thus terminated early. The study concluded:” Carboplatin and paclitaxel is not an active regimen in patients with metastatic papillary RCC. Future studies should explore the role of this or similar regimens in collecting duct carcinoma”. Paclitaxel and Carboplatin in Treating Patients With Locally Advanced or Metastatic Renal Cell Cancer, NCT00077129 has been completed but not yet published.

Case reports suggest high response for gemcitabine. A 2011 phase II study of gemcitabine and doxorubicine was dissapointing. The conclusion fo this study by Robaud G. et al was that , “showed a lower response rate than previously reported. Nevertheless, some patients had prolonged survival outcomes. This combination could be an option in sarcomatoid histology (NCCN guidelines) or rapidly progressive disease, but this population represents an unmet medical need.”.

Currently, there are no guidelines or consensus that this drug should be used, alone or in combinaiton for sarcomatoid variant of renal cell cancer.

Hoshi S, Satoh M, Ohyama C, Hiramatu M, Watanabe R, Hagisawa S, Endo M, Arai Y.Active chemotherapy for bone metastasis in sarcomatoid renal cell carcinoma. Int J Clin Oncol. 2003 Apr;8(2):113-7.

N. Bangalore , P. Bhargava , M. J. Hawkins , and P. Bhargava
Sustained response of sarcomatoid renal-cell carcinoma to MAID chemotherapy: Case report and review of the literature
Ann Oncol 12: 271-274.

Kathryn A. Bylow et al, Phase II Trial of Carboplatin and Paclitaxel in Papillary Renal Cell Carcinoma Journal Clinical Genitourinary Cancer
Volume 7, Number 1 / January 2009 Pages 39-42

J. Verweij, Phase II studies of docetaxel in the treatment of various solid tumoursEuropean Journal of Cancer Volume 31, Supplement 4, October 1995, Pages S21-S24

Fujiwara Y, Kiura K, Tabata M, Takigawa N, Hotta K, Umemura S, Omori M, Gemba K, Ueoka H, Tanimoto M.Remarkable shrinkage of sarcomatoid renal cell carcinoma with single-agent gemcitabine.
Anticancer Drugs. 2008 Apr;19(4):431-3.

Roubaud G, Gross-Goupil M, Wallerand H, de Clermont H, Dilhuydy MS, Ravaud A
Combination of gemcitabine and doxorubicin in rapidly progressive metastatic renal cell carcinoma and/or sarcomatoid renal cell carcinoma. Oncology. 2011;80(3-4):214-8.

Avastin for renal cell cancer – pro

admin — Sun, 02 Sep 2012 14:34:09 +0000

^{Avastin is an effective treatment for renal cell carcinoma. It is FDA approved for the treatment of metastatic renal cell carcinoma in combination with interferon alfa. This is based on the AVOREN study, which revealed that the addition of Avastin® (bevacizumab) to interferon improves progression-free survival when used as initial therapy among patients with metastatic renal cell carcinoma(mRCC). The details of this randomized trial were presented at a plenary session of the 2007 annual meeting of the American Society of Clinical Oncology (ASCO.Researchers from France recently conducted a Phase III clinical trial in which Avastin plus interferon was compared with interferon alone in the treatment of metastatic RCC. This trial included approximately 600 patients who had not received prior therapy. Patients treated with Avastin/interferon had a median progression-free survival of 10.2 months, compared with 5.4 months for those treated with interferon alone. Responses occurred in 31% of patients treated with Avastin/interferon, compared with only 13% for those treated with interferon alone. The most common side effects associated with treatment with Avastin were bleeding, high blood pressure, and protein in the urine. There was a trend for improved survival (0.06) in the Avastin group.}

^{Several studies indicate that Avastin alone is also effective for renal cell carcinoma. A randomized, double-blind, Phase II trial was conducted comparing placebo with bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks in 166 patients with renal cancer. Subjects were randomized to three groups: 40 to placebo, 37 to low-dose bevacizumab, and 39 to high-dose bevacizumab. The investigators reported that there was a significant prolongation of the time to progression of disease in the high-dose–antibody group as compared with the placebo group (hazard ratio, 2.55; P<0.001). Although there were no significant differences in survival, this study cannot rule out such a benefit due to the fact that the study was too underpowered to detect differences in survival between treatment groups that may be clinically significant. According to updated results from a phase II clinical trial presented at the 23rd annual Chemotherapy Foundation Symposium, treatment with the combination of Tarceva® (erlotinib) and Avastin® (bevacizumab) resulted in good survival among patients with metastatic renal cell carcinoma.}

^{Current NCCN guidelines recommend Avastin as an option for crossover therapy of renal cell carcinoma after first line therapy with IL2, sorafenib or sunitinib and for first line with interferon.}

Coppin C, Porzsolt F, Awa A, et al. Immunotherapy for advanced renal cell cancer. Cochrane Database Systematic Rev. 2004;3:CD001425.

Escudier B, Koralewski P, Piuzanska A, et al. A randomized, controlled, double-blind Phase III study (AVOREN) of bevacizumab/interferon/a2a vs placebo/interferon-a2a as first-line therapy in metastatic renal cell carcinoma. Proceedings from the American Society of Clinical Onclology. Chicago, IL. 2007 Abstract # 3.

NCCN KID-7, 2011

EU Guidelines on Renal Cancer 2010

Ana M. Molina and Robert J. Motzer Clinical Practice Guidelines for the Treatment of Metastatic Renal Cell Carcinoma: Today and Tomorrow The Oncologist February 2011 vol. 16 Supplement 2 45-50

New Drug: Votrient for renal cell cancer – pro

admin — Sat, 01 Sep 2012 22:20:31 +0000

Votrient(pazopanib) is a multi-targeted tyrosine kinase inhibitor and it is currently approved for renal cell carcinoma. VOTRIENT® is indicated for the treatment of patients with advanced renal cell carcinoma(RCC).

Pazopanib has not been compared to other agents for the treatment of RCC in clinical trials. Two published clinical trials have evaluated pazopanib in RCC. In one randomized, double-blind trial, median progression free survival was improved with pazopanib (9.2 months) compared to placebo (4.2 months, p<0.0001); more patients experienced a complete or partial response with pazopanib (30%) compared to placebo (3%, p<0.001). In one open-label trial, 35% of patients experienced a complete or partial response. Median progression free survival was 52 weeks. The median duration of response ranged from 58.7 to 68 weeks.
The National Comprehensive Cancer Network (NCCN) recommends Votrient for RCC as follows:
• First-line therapy as a single agent for relapsed or medically unresectable stage IV disease with predominant clear cell histology in selected patients (grade 1)
• Subsequent therapy as a single agent for relapsed or medically unresectable stage IV disease with predominant clear cell histology in patients who have progressed on prior first-line therapy (grade 1)
This drug is also recommended by NICE.

Bible KC, Smallridge R, Maples W, et al. Phase II trial of pazopanib in progressive, metastatic, iodine-insensitive differentiated thyroid cancers [Abstract 3521]. Journal of Clinical Oncology. 2009;27(15S).
GlaxoSmithKline. Votrient (pazopanib tablets) [product information]. Research Triangle Park, NC: GlaxoSmithKline; 2010.
McEvoy GK, ed. AHFS 2010 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists, Inc. 2010.
NCCN Drugs & Biologics Compendium™. Votrient™ (pazopanib). Copyright 20109, National Comprehensive Cancer Network (NCCN).

High dose interleukin 2 for renal cell carcinoma – pro

M Levin, MD — Thu, 21 Jun 2012 15:15:51 +0000

SHigh-dose interleukin-2 (IL-2) results in objective clinical regression of metastatic cancer in 15% to 17% of patients with melanoma and renal cell carcinoma. Durable complete regression of all metastases is seen in 6% to 8% of patients. Based on these findings, the U.S. Food and Drug Administration has approved the use of high-dose IL-2 for the treatment of patients with metastatic melanoma and renal cell carcinoma. Interleukin-2 administration is associated with many different side effects, and after many years of use, clinicians have learned how to safely administer high-dose IL-2. It is so toxic as to require an ICU or similar unit to be able to “carry” the patient through skin, kidney, GI toxicity.

Schwartzentruber DJ. Guidelines for the safe administration of high-dose interleukin-2.J.Immunother. 2001 Jul-Aug;24(4):287-93.

Schwartz RN, Stover L, Dutcher J. Managing toxicities of high-dose interleukin-2.Oncology (Williston Park). 2002 Nov;16(11 Suppl 13):11-20.