Surgery improves kidney cancer survival: study

NEW YORK, 26 dec 2008– Surgical removal of the kidney -- a procedure known as nephrectomy -- improves survival in patients with locally advanced renal cell carcinoma, the most common form of kidney cancer.

Dr. Pierre I. Karakiewicz from University of Montreal and colleagues determined survival rates for 43,143 patients treated with nephrectomy for advanced renal cell carcinoma that had not spread to other sites and a group of similar patients that did not have the surgery.

Death due to cancer was 5.8-fold higher for nonsurgical therapy than for nephrectomy, the team reports.

In a second analysis, where a subset of patients treated without surgery were matched with up to four surgically treated patients, there was still a 5.1-fold higher rate of cancer-specific mortality (death) in the nonsurgical group than in the nephrectomy group.

Overall, 5- and 10-year estimates of cancer-specific survival were 68.6 percent and 57.5 percent, respectively, for the nephrectomy group, compared with just 14.5 percent and 10.6 percent, respectively, for the nonsurgical therapy group.

This study, the investigators conclude, show that nonsurgical therapy is associated with a 44 percent to 57 percent worse survival than nephrectomy.

"Based on these findings, nephrectomy should be considered as the treatment of choice for patients with locally advanced renal cell carcinoma," they conclude.

SOURCE: BJU (British Journal of Urology) International, December 2008.

Landmark UCLA study finds aggresive, personalized treatment increases kidney cancer patient survival

Study will allow doctors to better predict which patients will do well and select those who may respond to targeted therapies

03 novc 2008--A study of nearly 1,500 patients treated for kidney cancer at UCLA in the last 15 years shows that an aggressive, tailored treatment approach results in better survival rates and uncovered subsets of kidney cancer that behave differently and need to be treated accordingly.
The one-size-fits-all approach traditionally used in kidney cancer treatment should be changed based on the results of the study, the longest to date to analyze kidney cancer patients and their outcomes, said Dr. Arie Belldegrun, senior author of the study, a professor of urology and a researcher at UCLA's Jonsson Comprehensive Cancer Center.
"This is the most important work that we've done out of the kidney cancer program at UCLA," Belldegrun said. "We outline the foundation for personalized kidney cancer therapy. We have shown that not all kidney cancer patients are the same, not all localized kidney cancers are the same and not all metastatic kidney cancers are the same."
The study appears in the Nov. 1, 2008 issue of Cancer, the peer-reviewed journal of the American Cancer Society.
The study found that patients with localized kidney cancer, cancer that has not spread to other organs, could have either low, intermediate or high risk cancers based on the chance for recurrence. Patients with cancers that have already spread also fell into similarly different subsets. Some have better outcomes while others may have very aggressive cancers that may not warrant treatment.
"We showed for the first time, using an integrated staging system developed at UCLA, that we can identify which patients with localized disease fall into the low, intermediate and high risk subsets and which patients with metastasized cancers are either low, intermediate or high risk patients," Belldegrun said. "Now we can make treatment decisions based on that."
If a patient with localized cancer is identified as low risk, his five-year survival rate is expected to be 97 percent, while his 10-year survival rate is 92 percent. An intermediate risk patient with localized disease would have a five-year survival rate of 81 percent and a 10-year survival rate of 61 percent. A high risk patient has a five-year survival rate of 62 percent, with a 10-year survival of 41 percent.
"All of these patients with cancers that have not spread present to their doctors with presumably localized disease and in the past they may have been treated the same way," Belldegrun said. "They need to be treated individually according to their risk levels."
The study showed that a patient with low-risk, localized kidney cancer could be treated only with surgery and expect an excellent outcome. Such a move would spare the patient from having to undergo radiation or immunotherapy, which result in harsh side effects. However, for a patient with high-risk, localized kidney cancer, surgery would not be enough. Additional therapy such as targeted treatments or immunotherapy should be considered in order to give the patient the best possible outcome.
In metastatic patients, someone with low-risk cancer should get very aggressive treatment, Belldegrun said, because there's a good chance the therapy will help the patient. Those with high-risk, metastatic disease won't get much, if any, benefit from treatment and may want to forego surgery and the toxic therapies.
"Our paper identifies, very precisely, which patients should get which therapies," Belldegrun said.
The study represents 15 years of experience in UCLA's leading-edge kidney cancer program, an interdisciplinary approach to treating cancer that brings together medical oncologists, urologists, surgeons, clinical trials experts and scientists under one roof, a concept that was first conceptualized at UCLA. The study analyzed the first 1,492 patients treated in the program and "demonstrated that outstanding results can be achieved using this approach," Belldegrun said.
About 25 percent of the patients with metastatic kidney cancer achieved long-term responses – five to 15 year survivals – from their therapy, Belldegrun said. Less than 5 percent of metastatic kidney cancer patient typically achieve long term survivals or a cure when treated with conventional treatments.
"This is by far the best survival data in such a difficult group of patients," Belldegrun said. "This can be achieved today only in kidney cancer centers of excellence like we are operating at UCLA, where we have all the expertise at hand, the best scientists, clinicians and surgeons working together."
The results of the study come as new targeted therapies are being introduced specifically for kidney cancer. The U.S. Food & Drug Administration has recently approved three such drugs. Belldegrun said the survival rates detailed in their paper should be used as a benchmark to which these new therapies should be compared.
"While the field of kidney cancer is undergoing dramatic changes it is as yet still unclear how these changes are affecting patient outcome," the study states. "A critical assessment of the potential improvement in the new treatment era necessitates a comparison to a known benchmark. We present long-term, single institution data to provide a thorough understanding of the results that have been achieved until now using a consistent, aggressive approach for localized and metastatic disease. For future patient care, it will be important to select patients that will do best using existing therapies, and those who should be treated using the newly approved treatments."
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Other lead investigators on the study include Dr. Fairooz Kabbinavar, medical director of the kidney cancer program at UCLA and a professor of hematology/oncology, and Dr. Allan Pantuck, director for translational research and an associate professor of urology. Both are scientists with the Jonsson Cancer Center.
UCLA's Jonsson Comprehensive Cancer Center comprises about 235 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2008, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for nine consecutive years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.

Vaccine Therapy Disappoints for Kidney Cancer

By Crystal Phend
HOUSTON, 5 july 2008-- The tumor-derived vaccine vitespen (Oncophage) does not prevent renal-cell carcinoma recurrence or improve survival despite promising early results, researchers said.
The combined rate of recurrence and death was similar through almost two years of follow-up in nephrectomy patients given the autologous vaccine as adjuvant therapy compared with observation (37.7% versus 39.8%, P=0.506), reported Christopher Wood, M.D., of the University of Texas M.D. Anderson Cancer Center here, and colleagues online in The Lancet.
After an additional 17 months of follow-up in the randomized phase III trial, survival still showed no improvement with the vaccine against peptide-bound heat-shock protein purified from patients' tumors (P=0.896).
An exploratory analysis of early-stage kidney cancer patients (stage I or II disease) had signaled a possible reduction in recurrence with the vaccine (15.2% versus 27%, hazard ratio 0.576, P=0.056), which the researchers said would require further validation.
However, in an accompanying editorial, James C. Yang, M.D., of the National Cancer Institute in Bethesda, Md., criticized such "use of post-hoc subset analyses to salvage underpowered studies." He criticized the study and the sponsoring company for conduct that included differences between the published results and those reported in a company press release.
A press release from Antigenics, the manufacturer of vitespen, on April 8, 2008 highlighted "a clinically significant improvement in recurrence-free survival of approximately 45% over patients in the observation arm" among the intermediate-risk patients.
But, Dr. Yang wrote, the company did not point out that this was not a prespecified analysis nor was a further subset analysis of 25th percentile data mentioned in the release.
"The credibility of the field of cancer immunotherapy is weakened when some investigators, and particularly vaccine companies, cannot accept the results of randomized trials," he said.
A spokesperson for the company called these comments inaccurate and inapppropriate. "We've been fully transparent with the data," he said.
He noted that the press release discussed more up-to-date data than those appearing in The Lancet. Longer follow-up yielded stronger, significant P-values in findings filed in a regulatory submission that led to approval for intermediate-stage kidney cancer in Russia, he said.
While acknowledging caution with non-prespecified endpoints, such as survival at the 25th percentile, "it gives you the sense the patients are trending in the right direction," the spokesperson said.
On the basis of signals of clinical activity and tumor-specific immune responses in phase I and II trials in renal-cell carcinoma and other cancer as well as a phase III study in melanoma, vitespen looked promising for the phase III trial in renal cell cancer.
The intent-to-treat analysis of the open-label trial included 728 patients in North America, Europe, Russia, and Israel.
Patients were randomized to observation after surgery or treatment with vitespen intended to start within eight weeks of surgery. The vaccine was given at a dose of 25 μg intradermally once a week for four weeks, then every two weeks until vaccine supply depletion or disease progression for a total of 12 injections on average.
However, the trial stumbled early on, with more than 40% of the reported events that triggered the final analysis on Nov. 4, 2005 rejected by the adjudication committee as not being true events of recurrence.
A total of 124 patients had remaining disease at baseline after surgery rendering them ineligible for the trial. And of these, 92 were reported to have disease recurrence whereas they actually had disease progression.
The researchers cautioned that their finding of a nonstatistically significant reduction in recurrence events among patients with stage I or II kidney cancer with vitespen, while in a prespecified analysis, could have been a result of statistical noise resulting from the small sample size of patients with more advanced cancer.
"Nonetheless, the observation that treatment with vitespen confers an apparent clinical benefit to patients with earlier stage disease with better prognosis is biologically plausible," they said.
Later-stage tumors have more mechanisms to resist immunotherapy, they noted. "Additional research is thus warranted to further explore the use of vitespen in patients with early stage renal cell carcinoma."
Although the lack of treatment-related grade 3 or 4 adverse events makes it easier to accept any implication of efficacy, Dr. Yang warned that "commercially driven efforts that spin or obfuscate the conclusions of such a trial should be vigorously resisted because such efforts severely erode its value."
The study was funded by Antigenics of New York.
Dr. Woods and several co-authors reported consulting for and receiving honoraria from Antigenics. Co-authors reported other conflicts of interest for Antigenics, including employment, founding the company, and owning stock in the company.
Dr. Yang reported no conflicts of interest.
Primary source: The LancetSource reference:Wood C, et al "An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial" Lancet 2008. Additional source: The LancetSource reference: Yang JC "Vitespen: a vaccine for renal cancer?" Lancet 2008.

Kidney cancer may be linked to multiple myeloma

By Megan Rauscher
21 april 2008--For the first time, researchers have evidence of an association between renal cell carcinoma and multiple myeloma, a type of blood cancer, one that "cannot be explained by random incidence alone," they say.
"I think general oncologists as well as myeloma and renal cancer physicians should be aware of this association," Dr. Mohamad A. Hussein of the H. Lee Moffitt Cancer and Research Institute in Tampa, Florida, noted in comments to Reuters Health.
Renal cell carcinoma begins in the kidney cells and although it may progress slowly, it is very resistance to chemotherapy. Multiple myeloma, which may also progress slowly, is likewise resistant to treatment. It begins in the blood's plasma cells, a type of white blood cell that is part of the immune system. Over time, myeloma cells build up in bone marrow and then in the solid parts of bone.
In a review of data from patients referred to the Cleveland Clinic between 1990 and 2005, Hussein and colleagues identified 1,100 patients with multiple myeloma, 2,704 with renal cell carcinoma, and 8 with both types of cancer.
In 4 of the 8 patients, renal cell carcinoma was diagnosed 3 to 46 months after the multiple myeloma diagnosis. In the remaining 4, renal cell carcinoma was diagnosed 1 to 108 months before the multiple myeloma. Seven of the 8 patients were first diagnosed with renal cell carcinoma on the right side.
"The probability of this association was much higher than that expected in the general population," the researchers note in the medical journal BJU International. "No clear treatment-related, environmental, genetic or immune-mediated common factors can fully explain this association."
The investigators point out that interleukin-6 supports the growth and expansion of both types of cancer. Interleukin-6 is a "cytokine" that normally enhances the body's immune response to disease and infection.
"I think the take-home message," Hussein said, "is that after active therapy for myeloma, if the kidney lesion does not clear -- especially if it is affecting the right kidney -- renal cell cancer should be considered."
In this study, when myeloma was the first malignancy diagnosed, "the renal cell carcinoma was at a very early stage and therefore surgical exploration is critical."
SOURCE: BJU International, March 2008.

Radical Nephrectomy for Kidney Cancer Linked to Lower Survival in Younger Patients

By Charles Bankhead
ROCHESTER, Minn., Jan. 9 -- Radical nephrectomy carried a twofold increase in mortality risk compared with partial nephrectomy in patients younger than 65 with small renal masses, investigators from the Mayo Clinic found.
In an analysis that included patients of all ages, however, radical nephrectomy was associated with a nonsignificant 12% increased risk compared with partial nephrectomy, R. Houston Thompson, M.D., and colleagues reported in the February issue of the Journal of Urology.
"For patients with small kidney tumors, removal of the entire kidney may be associated with long-term consequences that we did not previously recognize, compared with removal of just the tumor," said Dr. Thompson, now at Memorial Sloan-Kettering Cancer Center.
The authors of two accompanying commentaries warn against pointed out limitations of the study and warned against overinterpretation of the results.
"Recent evidence suggests that there is a graded impact on survival based on declining overall kidney function," Dr. Thompson said. "So as kidney function declines, the risk of heart attacks and heart-related events goes up, and consequently, the risk of death from these events goes up."
Recent studies have suggested that radical nephrectomy for renal tumors 4 cm or smaller significantly increases the risk of chronic renal failure compared with partial nephrectomy. Because renal failure is associated with cardiovascular morbidity and mortality, radical nephrectomy might decrease survival in patients with small renal tumors, the authors noted.
Numerous studies have demonstrated equivalent oncologic outcomes between the two procedures; however, data on overall survival have been lacking.
In an effort to clarify the association between surgical technique and overall survival, Dr. Thompson and colleagues analyzed data from the Mayo Clinic's nephrectomy registry. They limited the analysis to patients with sporadic, unilateral, solitary, and localized renal masses 4 cm or smaller treated by radical or partial nephrectomy from 1989 through 2003.
After exclusion of patients with only one kidney or impaired renal function, 648 patients were available for analysis. The primary endpoint was overall survival.
Radical nephrectomy was performed in 290 patients and partial nephrectomy in 358. At a median follow-up of 7.1 years, 502 patients remained alive.
In the overall analysis, radical nephrectomy did not increase all-cause mortality relative to partial nephrectomy (relative risk: 1.12, P=0.52). However, the analysis revealed a significant difference with patient age.
Stratification of the patient population at the median age of 65 resulted in 327 patients younger than the median. In that younger subgroup partial nephrectomy was associated with a relative risk of 2.16 (P=0.02) for death from any cause compared with partial nephrectomy.
The association remained significant after adjusting for year of surgery, preoperative creatinine, Charlson-Romano index, preoperative symptoms, diabetes, and tumor histology.
The data add to the debate about underuse of partial nephrectomy, the authors stated. Over the past decade many urologic surgeons have come to accept partial nephrectomy as the standard of care for small renal tumors. However, only 20% of renal tumors 2 to 4 cm are treated with partial nephrectomy in the U.S. and only 4% in England.
About two thirds of all renal masses are small and incidentally detected. With increasing experience, complications of partial nephrectomy have been minimized, they said.
"Thus, it remains perplexing why so few patients are treated with partial nephrectomy," the authors commented.
In an editorial that accompanied the report, Steven C. Campbell, M.D., of the Cleveland Clinic, cautioned against overinterpretation of the findings and overlooking the study's limitations.
Cause of death is not addressed, he said. And the major finding applied to a subgroup of patients, not the overall population.
"The exploration of enough subgroups increases the chances of a positive and potentially misleading finding," Dr. Campbell stated.
The study should be considered hypothesis generating, not definitive, he concluded.
In a second editorial commentary, Lee Richstone, M.D., and Louis R. Kavoussi, M.D., of North Shore Long Island-Jewish Health System in New Hyde Park, N.Y., pointed out that patients treated by radical nephrectomy were followed for 9.4 years versus 5.6 years for the partial nephrectomy group. That disparity alone might account for the observed difference.
Despite the limitations, the study generates a provocative question, wrote Drs. Richstone and Kavoussi: Does the additional nephron loss associated with radical nephrectomy result in increased mortality?
"This questions remains unanswered and we should await data … to determine the true impact of radical surgery on patient mortality," they concluded.
Neither the primary authors nor the editorialists disclosed potential conflicts.
Primary source: Journal of UrologySource reference:Thompson RH, et al "Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy" J Urol 2008; DOI:10.1016/j.juro.2007.09.077.

Bevacizumab-Interferon Duo Improves Progression-Free Survival in Kidney Cancer

By Charles Bankhead
VILLEJUIF, France, Dec. 20 -- When bevacizumab (Avastin) is added to interferon, the combo significantly improves progression-free survival in advanced renal cell carcinoma, investigators here reported.
The combination therapy doubled the duration of progression-free survival compared with interferon alone, Bernard Escudier, M.D., of Gustave Roussy Institute, and colleagues reported in the Dec. 22 issue of The Lancet. The frequency, severity, and mortality of adverse events did not differ between patients treated with interferon alone or interferon plus bevacizumab.
"The data presented here raise intriguing questions regarding the future of therapy for metastatic renal cell carcinoma," the authors said. "The availability of a variety of active agents provides increased treatment options and the opportunity to provide several lines of therapy and improved survival."
Metastatic renal cell carcinoma is resistant to conventional therapy. Until recently, standard systemic therapy consisted of interleukin-2 or interferon, both of which produced modest response rates at a price of substantial toxicity.
More recently, the tyrosine kinase inhibitors sorafenib and sunitinib have been approved for treatment of metastatic renal cell carcinoma. Both have been shown to improve progression-free survival in patients whose disease did not respond to interferon or IL-2, the authors noted. However, only the mammalian target of rapamycin inhibitor temsirolimus has improved overall survival compared with interferon alone.
In preliminary studies in advanced renal cell carcinoma, bevacizumab, a humanized monoclonal antibody that inhibits vascular endothelial growth factor, improved progression-free survival and time to progression, and induced durable responses lasting three to five years in some patients.
Dr. Escudier and colleagues reported findings from a randomized, double-blind phase III trial involving 649 patients with untreated metastatic disease. The patients were randomized to interferon alfa-2a (9 MIU subcutaneous three times a week) plus bevacizumab (10 mg/kg every two weeks) or interferon alfa-2a and placebo.
The primary endpoint was overall survival, and secondary endpoints included progression-free survival and safety. At a planned interim analysis, investigators changed the primary endpoint to progression-free survival, acknowledging that new second-line therapies that had become available during the trial could confound the results.
At the time of unblinding. 230 of 325 patients on combination therapy had progressed, as had 275 of 316 in the interferon-placebo group. Additionally, 114 deaths had occurred in the bevacizumab arm and 137 in the placebo arm.
Median duration of progression-free survival was 10.2 months with bevacizumab versus 5.4 months with placebo (P=0.0001).
"Increases in progression-free survival were seen with bevacizumab plus interferon alfa irrespective of risk group or whether reduced-dose interferon alfa was received," the authors reported.
The most common grade 3+ adverse events were fatigue (12% with bevacizumab versus 25% with placebo) and asthenia (10% with bevacizumab and 7% with placebo). Adverse event-related mortality was 2% in each treatment arm.
In a commentary that accompanied the article, Robert J. Motzer, M.D., and Ethan Basch, M.D., of Memorial Sloan-Kettering Cancer Center in New York, noted that response to therapy was assessed by individual investigators. "Lack of independent review of response might have affected the proportion of patients with reported responses, and therefore affected perceived progression-free survival outcomes."
Dr. Escudier disclosed consulting fees and honoraria from Roche, Bayer, Wyeth, Pfizer, Inate, and Antigenics. Dr. Motzer disclosed honoraria from Bayer/Onyx, current research funding from Genentech, Wyeth Research, Pfizer, and Novartis, and past research funding from Roche and Schering-Plough.
Primary source: The LancetSource reference:Escudier B, et al "Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomized, double-blind phase III trial" Lancet 2007; 370: 2103-2111. Additional source: The LancetSource reference: Motzer R, Basch E, "Targeted drugs for metastatic renal cell carcinoma" Lancet 2007; 370: 2071-2073.

Another VEGF Inhibitor Shows Activity Against Kidney Cancer

PARIS, Oct. 30 -- Treatment with axitinib resulted in at least a partial response in nearly half of patients with cytokine-refractory metastatic kidney cancer, investigators in a multinational trial have found.
The investigational vascular endothelial growth factor (VEGF) inhibitor resulted in two complete responses and 21 partial responses in 52 patients, Olivier Rixe, M.D., of the University of Paris, and colleagues, reported in the November issue of The Lancet Oncology.
Additionally, they said, in 22 patients the disease stabilized for at least eight weeks, and in 13 patients, for 24 weeks or longer.
"The objective response and time to progression in our study suggest that axitinib might be a promising drug in the treatment of patients with metastatic renal-cell cancer; although a randomized controlled trial is needed to confirm this finding," the authors concluded.

Biological therapy with interferon alfa or interleukin-2 has only modest activity in good-risk patients with renal-cell carcinoma. Antiangiogenic therapies have improved survival in the disease, and two agents, sunitinib and sorafenib (also VEGF inhibitors) have been approved for treatment of metastatic renal-cell carcinoma.
Axitinib is an oral selective inhibitor of VEGF receptors 1, 2, and 3. Preclinical studies suggested that the agent had antitumor activity related to antiangiogenic effects, and phase 1 clinical investigation provided additional evidence of activity in patients with various advanced solid tumors.
Dr. Rixe and investigators in Europe and the United States continued the evaluation of the drug in a phase II trial involving patients with metastatic renal-cell carcinoma unresponsive to cytokine therapy. Treatment began at a dose of 5 mg twice daily. The dose could be titrated upward by 20% after eight weeks if a patient had no tumor response and no grade 2+ toxicity.
The primary endpoint was objective response. Secondary endpoints were response duration, time to progression, overall survival, safety, pharmacokinetics, and patient-reported health-related quality of life.
In an intention-to-treat analysis, axitinib resulted in an overall response rate of 44.2%. The median response duration was 23 months. However, 12 of 23 initial responders progressed with a response that lasted between 4.2 and 26.5 months. An additional 42.3% of patients had prolonged disease stabilization.
Four patients had early disease progression, and three had incomplete data. The median time to progression was 15.7 months, and the median overall survival was 29.9 months.
The most common treatment-related adverse events were diarrhea, hypertension, fatigue, nausea, and hoarseness. Thirty patients had treatment-related hypertension that resolved with antihypertensive therapy in 22 cases. Seven of the remaining eight patients had a history of hypertension.
Dr. Rixe disclosed that he has been a consultant to Pfizer and received honoraria for participation in Pfizer-supported activities. The study was supported by Pfizer. Primary source: The Lancet OncologySource reference: Rixe O, et al "Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study." Lancet Oncol 2007; 8: 975-984.

Tumor-Zapping Technique Fights Kidney Cancer

Fri Aug 3, 7:02 PM ET
FRIDAY, Aug. 3 (HealthDay News) -- A heat-based technique called "CT-guided radiofrequency ablation" was almost 100 percent successful in destroying small malignant kidney tumors in a study of more than 100 patients, new research shows.
Radiofrequency ablation has been used successful in liver tumors since the early 1990s. A needle-like treatment probe, guided by computer tomography (CT), is inserted into the tumor where it emits a high-frequency alternating current. The current heats the tumor tissue and destroys it. Radiofrequency ablation is an outpatient procedure in which the patient is sedated but conscious, and a local anesthetic is used at the puncture site.
The technique targeted tumors ranging in size from 0.6 centimeters to 8.8 centimeters in size. A total of 125 tumors in 104 patients were treated between 2000 and 2006. Of the 95 tumors that were smaller than 3.7 cm, all were completely eradicated by a single treatment, the researchers reported in the August issue of the American Journal of Roentgenology.
Seven of the remaining tumors were eradicated after a second treatment, the team added, for a total 93 percent success rate for all 125 tumors. The tumors were still gone 14 months after treatment. Of the 104 patients in the study, 101 went home the same day.
"This is the largest treatment group to date of patients with biopsy-proven renal malignancies," lead author Dr. Ronald J. Zagoria, of Wake Forest University Baptist Medical Center in Wnston-Salem, N.C., said in a prepared statement. "The results, a high cure rate and low complication rate, establish that at institutions with experience doing this procedure, this is an alternative method for treating small renal malignancies in patients who are not good surgical candidates," he said.
His team noted that the technique is best used for small tumors. Although it can be effective in larger tumors, there is always the risk of incomplete destruction. Further, tumors located near the middle of the kidney pose a particular challenge, because they are close to large blood vessels or the ureter, the tubes that transport urine from the kidney to the bladder.
Zagoria's group cautioned that surgery is still the preferred method of fighting kidney cancer in patients who are young, healthy and have two kidneys because there is no data available for long-term follow-up on the effects of radiofrequency ablation.
There are more than 51,000 new cases of kidney cancer every year in the United States and 12,000 deaths from the disease, according to the U.S. National Cancer Institute.
More information
To learn more about kidney cancer, visit the U.S. National Cancer Institute.

Bevacizumab Added to Kidney Cancer Therapy Extends Survival

June 13, 2007 (Chicago) — A new trial shows that adding bevacizumab (Avastin, Genentech) to interferon nearly doubles progression-free survival in patients with renal cell carcinoma. "When you look at the data, the combination is better than interferon alone," lead investigator Bernard Escudier, MD, head of the immunotherapy unit at the Gustave Roussy Institute, in Villejuif, France, told Medscape. "In my opinion, it's at least as safe and well tolerated as interferon alone," he said. The findings were presented during the plenary session here at the 43rd annual meeting of the American Society of Clinical Oncology.
"This is an important and well-conducted study by a distinguished colleague," Ronald Bukowski, MD, director of the experimental therapeutics program at the Cleveland Clinic Taussig Cancer Center, in Ohio, said during the discussion period following the presentation.
During an interview, Dr. Escudier said he was somewhat surprised by the results. "We did not expect to find such a big difference between treatments. We had anticipated about a 30% improvement and yet we saw a doubling of progression-free survival. That was unexpected."
Dean Bajorin, MD, from Memorial Sloan-Kettering Cancer Center, in New York, and moderator of a press conference outlining the findings, called the progression-free survival data "striking," and he commended this group and others for moving the standard of care for kidney cancer forward.
Until recently, there were few options for patients with renal cell carcinoma. In the past 18 months, however, 2 targeted therapies have shown efficacy and received approval from the US Food and Drug Administration: sorafenib (Nexavar, Onyx Pharmaceuticals) and sunitinib (Sutent, Pfizer). "We're in a very exciting time in kidney cancer research with a number of new targeted therapies becoming available," Dr. Escudier told reporters.
Bevacizumab is currently approved for the treatment of advanced colorectal and nonsmall cell lung cancers. It is a monoclonal antibody that inhibits tumor angiogenesis by targeting vascular endothelial growth factor. In the current analysis, known as the AVOREN trial, investigators studied the effect of adding bevacizumab to interferon (Roferon, Roche) as a first-line treatment for advanced kidney cancer.
In this randomized, double-blind, placebo-controlled, phase 3 study, the European researchers looked at nephrectomized patients with renal cell carcinoma. They received interferon alpha 2a plus bevacizumab at a dose of 10 mg/kg every 2 weeks or placebo until disease progression.
Need More Long-Term Toxicity Data and Information on Grade 3 and 4 Adverse Events
Discussing the findings, Dr. Bukowski pointed to a number of limitations to the trial. He suggested that a third study arm, a bevacizumab monotherapy group, would have been useful. "Previous phase 2 data of bevacizumab suggest the benefit seen is predominantly due to this agent. A monotherapy comparator arm would therefore have been helpful in determining this," he said.
Dr. Bukowski also noted that the data are preliminary and additional information on overall toxicity is needed, including on long-term effects and grade 3 and 4 adverse events.
With new alternatives available, interferon is no longer considered the standard of care for most patients with kidney cancer. Future studies are likely to test bevacizumab as a single agent for first-line treatment of renal cell carcinoma by comparing it head to head with sorafenib and sunitinib. Additional trials are also anticipated to test bevacizumab in combination with these products and with the recently approved drug temsirolimus (Torisel, Wyeth).
"The future lies not in the comparison of these drugs," Dr. Escudier told Medscape, "but in the combinations of these products."
American Society of Clinical Oncology 43rd Annual Meeting: Abstract 3. Presented June 4, 2007.

Temsirolimus Wins FDA Okay to Prolong Survival in Advanced Kidney Cancer

PHILADELPHIA, May 30 -- The drug temsirolimus (Torisel) prolongs survival in patients with metastatic renal cell carcinoma, researchers here reported today.
And in a rare confluence of research results and regulatory action, on the same day that the pivotal randomized trial was published in the New England Journal of Medicine the drug was approved by the FDA for the indication.
For patients getting the drug, median survival was 3.6 months longer than for those getting standard treatment with interferon alfa, Gary Hudes, M.D., of the Fox Chase Cancer Center, and colleagues in the Global ARCC Trial, reported in the May 31 issue of the NEJM.
A third arm of the industry-sponsored study, combining temsirolimus and interferon alfa, did not show any survival benefit over interferon alfa alone, Dr. Hudes and colleagues found.
"This is the first study to show that a new drug can improve overall survival for patients with metastatic renal cell cancer," Dr. Hudes said.
Early last year, sutinib (Sutent) was approved to treat metastatic renal cell carcinoma, but the studies involving that drug showed improvement in progression-free survival, rather than overall survival.
Similarly, sorafenib (Nexavar) was approved in December 2005 on the basis of a delay in disease progression in renal cell carcinoma.
While the survival improvement with temsirolimus therapy is "modest," Dr. Hudes said, patients in the study had very advanced tumors.
"It would be reasonable to hypothesize that temsirolimus could provide greater benefit to patients with less extensive metastatic disease," Dr. Hudes said.
The current study was stopped at the second interim analysis, the researchers said, when 446 of the 626 patients had died and there was significant evidence (at P<0.0135) that the drug was providing a benefit.
In the study, patients were randomized to 25 mg of temsirolimus intravenously once a week; to interferon alfa, at a dose escalating from three million to 18 million units, subcutaneously three times a week; or to a combination of 15 mg of temsirolimus weekly and six million units of interferon alfa three times a week.
The study found:
Median survival for patients getting temsirolimus was 10.9 months, compared with 7.3 months for interferon alfa and 8.4 months for the combination.
For temsirolimus patients, the hazard ratio for death, compared to interferon alfa, was 0.73 (with a 95% confidence interval from 0.58 to 0.92), which was significant at P=0.008.
Overall survival for patients in the combination group did not differ significantly from those getting interferon alfa.
Dr. Hudes and colleagues said the lack of efficacy in the combination group may have been a result of the lower dose of temsirolimus.
The study also showed a significantly longer period of progression-free survival (P<0.001) for patients getting temsirolimus, compared with those on interferon alfa, the researchers said.
Temsirolimus was better tolerated than interferon-alfa, with 67% of patients in the temsirolimus group having Grade 3 or 4 adverse events, compared with 78% of interferon patients and 87% of patients in the combination group. Both differences were significant at P=0.02.

Sutent achieves first line EAU approval for kidney cancer

EAU recommendation closely follows EU marketing authorization for Sutent
Berlin, March 22 – Sutent® (sunitinib malate) has received a European Association of Urology (EAU) recommendation, as first-line therapy in patients with metastatic renal cell carcinoma of good and intermediate risk, just two months after gaining EU marketing authorization for first line use in all patients with advanced and/or metastatic renal cell carcinoma (mRCC).1 These new EAU guidelines, issued today in Berlin, put Sutent®, the first multi-targeted tyrosine kinase inhibitor to be approved in the EU for first-line use in mRCC, at the forefront of drug therapy for this devastating condition.
Sunitinib malate is an oral therapy belonging to a new class of dual-action multi-targeted drugs that attack cancer by inhibiting tumor growth and starving the tumor of blood, thereby reducing its ability to continue to divide and grow.
"There is strong clinical evidence to support the use of sunitinib malate to achieve significantly better progression free survival than was possible with previous standard of care therapy, interferon-alpha (IFNα). The 1st line recommendation of sunitinib malate in the EAU Guidelines is an important step forward in ensuring that this exciting new treatment option becomes a new standard of care in mRCC therapy across Europe", said Prof. Kurt Miller, member of the executive board of the German Working Group for Urological Cancer (AUO) and Head of Department of Urology, Charité Campus Benjamin Franklin, Berlin.
http://www.eurekalert.org/pub_releases/2007-03/r-saf032207.php