Kidney Cancer

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.

The US Food and Drug Administration (FDA) recently approved sunitinib malate (Sutent) capsules for two types of cancer: advanced renal cell carcinoma and malignant gastrointestinal stromal tumor (GIST), after disease progression on or intolerance to the frontline drug imatinib mesylate (Gleevec).

For the first time, the US Food and Drug Administration (FDA) has granted a new oncologic drug product approval for indications for two different cancers simultaneously. The agency approved Sutent (suniti-nib, Pfizer) for the treatment of patients with gastrointestinal stromal tumors (GIST) whose disease has progressed on imatinib (Gleevec) or who are unable to tolerate imatinib. It also granted Sutent accelerated approval for treating advanced renal cell carcinoma (RCC).

The Food and Drug Administration (FDA) has approved Nexavar (sorafenib tosylate) tablets for the treatment of patients with advanced renal cell carcinoma. Nexavar, a multikinase inhibitor that has been shown to double progression-free survival in these patients, is the first FDA-approved treatment for this type of cancer in more than a decade, Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc.

Although resection currently remains the standard of care for renalcarcinoma, the search for less invasive treatments has led to alternativesurgical approaches. Even less invasive, and appropriate for manygroups of patients, is percutaneous radiofrequency ablation, which inducestumor necrosis via lethal hyperthermia. Multiple series of renaltumors treated with percutaneous ablation in vivo and left in situ havebeen published; these series reveal that for small renal tumors,radiofrequency ablation results in complete necrosis at imaging in 79%to 100% of cases. Because current results come from tumors left in situwith short postablation follow-up, long-term results are necessary tocompare outcomes to surgical standards. Complication rates are lowerthan those following partial nephrectomy. Future reports will shed lighton the long-term outcomes of percutaneous ablation and the relativeadvantages and disadvantages of various technologies for thermal ablation.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

ASCO - In a large randomized double-blind phase III international trial in patients with previously treated metastatic renal cell cancer (RCC), the oral multikinase inhibitor sorafenib (BAY 43-9006) was well tolerated and doubled progression-free survival (PFS) vs placebo with best supportive care. Lead investigator Bernard Escudier, MD, presented interim results in 769 patients at the 41st Annual Meeting of the American Society of Clinical Oncology (LBA4510) on behalf of the BAY 43-9006 TARGETs Clinical Trial Group. The primary endpoint of the study, overall survival, has not yet been reached, he said, and will be reported at a later date.

Renal-cell carcinoma (RCC) is curable only in patients presenting with resectable, early-stage disease. Advanced local or metastatic disease carries an approximate 15% 5-year survival rate. However, the natural history of metastatic RCC is heterogeneous, and aggressive palliative treatment is recommended, especially for patients with a solitary metastatic site and good performance status.

This supplement to Oncology News International includes 17 reportson clinical trials of targeted therapies used alone, in combination with chemotherapy,or in combination with each other in the treatment of non–small-cell lung cancer (NSCLC),bronchoalveolar carcinoma, glioblastoma multiforme, and renal cell carcinoma.Included is a report on a novel targeted agent recently approved for treatment of NSCLC.

WASHINGTON-The 2004 US Surgeon General’s report on the health risks of smoking adds five cancers to the list of diseases caused by cigarettes-acute myeloid leukemia, and stomach, pancreatic, cervical, and kidney cancers. Other newly

SAN FRANCISCO-Renal cell carcinoma patients given a vaccine prepared from their own excised tumors experienced delayed time to progression (TTP) in a multicenter phase III trial, Christian Doehn, MD, of the University of Lübeck

This special supplement to Oncology News International includes 28 reportswith updated information on clinical trials investigating capecitabine and other agents inthe treatment of advanced colorectal and breast cancers, and other solid tumors.The reports summarize selected presentations from the 39th Annual Meeting of theAmerican Society of Clinical Oncology (ASCO) and related educational symposiaheld in conjunction with ASCO.

Drs. Uzair Chaudhary and GeraldHull provide a comprehensivereview of the role ofcytoreductive surgery in metastaticrenal cell carcinoma. This controversialtopic has been debated for manyyears. Metastatic renal cell carcinomacontinues to be a chemotherapyresistanttumor with a poor prognosis.About 30% of newly diagnosedpatients present with metastatic disease.In the metastatic setting, themost recognized treatment modalitiesinvolve the biologic agents interferon-alpha and interleukin-2 (IL-2,Proleukin). They produce an objectiveresponse rate of about 10% to15%, with approximately 5% of patientsachieving a durable completeresponse.

In this issue of ONCOLOGY,Chaudhary and Hull succinctlysummarize historical trends andcurrent thinking regarding the role ofcytoreductive nephrectomy in patientswith metastatic kidney cancer.Before the era of immunotherapy,there was little evidence that the naturalhistory of metastatic renal cellcarcinoma was improved by cytoreductivenephrectomy.[1] Patientswith metastatic cancer generally diefrom complications related to theirsites of tumor spread and not fromthe primary tumor; thus, on face value,it seems illogical to surgicallyremove the primary tumor in thesepatients.

Metastatic renal cell carcinoma is a devastating disease associatedwith poor survival. Immunotherapy is the mainstay of treatment, butresponse rates are low. The role of cytoreductive surgery in thepresence of metastatic disease is evolving. From both retrospective andrecently published randomized clinical trials, it is now apparent thatamong patients with metastatic renal cell carcinoma and good performancestatus, cytoreductive surgery followed by immunotherapy improvessurvival. However, this approach is likely to be detrimental inpatients with poor performance status. Clinical trials of novel agentsremain a priority in this disease.

FRAMINGHAM, Massachusetts-Genzyme Molecular Oncology has launched a phase I/II vaccine trial in advanced kidney cancer. The vaccine is made by combining the patient’s own cancer cells with dendritic cells using an electrical fusion approach. Up to 20 patients will be enrolled at Beth Israel Deaconess Medical Center and the Dana-Farber Cancer Institute, Boston.

Women who received radiation therapy for Wilms’ Tumor are at increased risk of complications during pregnancy and, therefore, should be carefully assessed and monitored by their obstetricians. These conclusions were part of a National Wilms’

Despite significant advances in the treatment of a variety of malignancies, highly effective therapies for most patients with metastatic renal cell carcinoma or metastatic melanoma are rare. Traditional oncologic treatment methods, such as

Interleukin-2 (IL-2, Proleukin) is one of the most effective agents in the treatment of metastatic renal cell carcinoma and metastatic melanoma. High-dose IL-2 therapy produces overall response rates of 15% to 20%;

Although high-dose interleukin-2 (IL-2, Proleukin), a highly toxic agent used in the treatment of renal cell carcinoma and melanoma, was initially associated with treatment-related mortality, it can, in the appropriate

Flavopiridol [2-(2-chlorophenyl 5 ,7-dihydroxy-8-[cis-(3-hydroxy-1-methyl-4-piperidinyl)-4H-1-benzopyran-4-one, hydrochloride] is a semisynthetic flavone with a novel structure compared with that of polyhydroxylated flavones, such as quercetin and genistein.[1] It is derived from rohitukine, an alkaloid isolated from the stem bark of Dysoxylum binectariferum, a plant indigenous to India.[2] Originally synthesized and supplied by Hoechst India Limited, flavopiridol is provided to the Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI) by Aventis Pharmaceuticals, Inc.

Phase II studies of single-agent docetaxel (Taxotere) yielded promising results in advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Antitumor responses have been demonstrated in previously treated and chemotherapy-naive TCC patients, as well as in a subgroup of patients with renal impairment unable to receive traditional cisplatin-based regimens.