ONCOLOGY Vol 17 No 5

Realizing that health-care providers must gather information, analyzeit, and share the results with others in order to learn frommedical errors, the House of Representatives passed the PatientSafety and Quality Improvement Act (H.R. 663). The Act encouragesproviders to do research and gather data about the causes of medicalmishaps and then share their findings with other providers in order tolearn ways to remedy systems and practices.

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.

High-dose myeloablative therapy with autologous or allogeneicstem cell rescue is an effective treatment strategy for non-Hodgkin’slymphoma (NHL), but NHL is much less likely to stay in remission afteran autologous transplant than after an allogeneic transplant. Thebenefit of undergoing an autologous transplant earlier in the course ofthe disease, especially for patients who present with intermediate orhigh scores on the International Prognostic Index of risk factors, is stillunclear. The addition of immunotherapy, biologic modifiers, andantibody therapy such as rituximab (Rituxan) or radiolabeled antibodyto the autologous transplant are approaches undergoing evaluation.Historically, there has been a high regimen-related mortality rateassociated with myeloablative allogeneic transplant that has made thisapproach a less appealing option for therapy. The use of nonmyeloablativeallogeneic transplants as treatment for NHL is less well studiedand remains to be defined.

The American Society of Clinical Oncology (ASCO) recentlycommended US Representatives Charlie Norwood (R-Ga) and LoisCapps (D-Calif) for introducing the Quality Cancer Care PreservationAct (H.R. 1622).

Hormonal therapies have longplayed an important role inthe treatment of metastaticand early-stage breast cancer. Afterdemonstrating equivalent efficacy andless toxicity than high-dose estrogen,tamoxifen-a selective estrogen-receptormodulator (SERM)-has beenwidely used for the treatment of metastaticbreast cancer.[1] Multiple randomizedadjuvant trials subsequently demonstrated that patients treated withtamoxifen experienced fewer breastcancer recurrences, leading to its widespreaduse in the adjuvant setting.[2]

Despite a dramatic decline in the incidence of gastric carcinoma inthe United States during the past century, treatment remains a challengingproblem for oncologists. Surgery continues to be the primarymodality for managing early-stage gastric cancer, but up to 80% ofpatients who undergo a "curative" resection develop locoregional ordistant recurrence. Given these sobering statistics, there has been greatinterest in developing strategies to prevent recurrences after surgeryand improve overall mortality. In this article, we review data onadjuvant treatment modalities for this disease, including radiotherapy,chemotherapy, combination chemotherapy and radiation, intraperitonealtreatment, and immunotherapy. We focus attention on the recentwidespread acceptance of adjuvant chemoradiotherapy, based on theresults of Intergroup trial 0116. Future strategies incorporating differentmodalities of treatment will be outlined.

Published literature indicates that the selective estrogen-receptormodulators (SERMs) tamoxifen and raloxifene (Evista) have favorableeffects on bone density, lipid profiles, and the incidence of secondbreast cancers, and unfavorable effects on the incidence of venousthrombosis and hot flushes. Tamoxifen increases the risk of endometrialcancer, but raloxifene does not. The effects of SERMs on sexualfunction and cognition are unclear. Because the selective antiaromataseagents are relatively new, the long-term effects of these agentson normal tissues are less well established. It appears that the nonsteroidalagents (anastrozole [Arimidex], letrozole [Femara]) and steroidal(exemestane [Aromasin]) antiaromatase agents may have differenteffects on normal tissues. Preliminary data demonstrate that anastrozoleincreases the risk of arthralgias and produces a decrease in bonedensity. In contrast, exemestane appears to favorably affect bonedensity and lipid profile, similar to tamoxifen and raloxifene. Theincidence of contralateral breast cancer is decreased in women onadjuvant anastrozole, but data for the other antiaromatase agents arenot yet available. Hot flushes have been reported with the use ofselective aromatase inhibitors, but their incidence seems to be comparableto what is reported with SERMs. Antiaromatase agents do notappear to cause venous thrombosis. More information about the effectsof the antiaromatase agents on normal tissue will become available asdata from ongoing adjuvant and chemoprevention trials are reported.Clinically, we should be conscious of the differences between antiaromataseagents and SERMs and their impact on women’s health.

With the advent of aromataseinhibitor use in the adjuvantsetting,[1] and the inceptionof trials examining their usefor breast cancer prevention, it seemsprudent to evaluate what we know todate about the long-term effects of these agents. Unfortunately, unlike selectiveestrogen-receptor modulators(SERMs)-in particular tamoxifen,[2]which has been used for over 15 yearsin patients with early-stage breast cancer-long-term data on the use of aromataseinhibitors are minimal.

We have seen major advancesin our understanding ofthe biology of malignantlymphoma in recent years. These advanceshave been reflected in thedevelopment of the Revised European-American (REAL)/World HealthOrganization (WHO) classificationof lymphoid malignancies, which incorporatesdata from immunophenotype,cytogenetic, and moleculargenetic studies as well as morphologicappearance and clinical behavior.The description of DNAmicroarray studies in diffuse largeB-cell non-Hodgkin’s lymphoma(NHL) has already generated usefulprognostic data and identified manypotential therapeutic targets.[1] Futurestudies may provide pharmacogenomicdata, which could predictresponse to therapy in individual patients,and thus allow a more tailoredtreatment approach.

It has been demonstrated that completemolecular remission in follicularlymphoma is associatedwith an improved outcome. Therefore,the object of modern therapyfor indolent lymphoma should be toachieve this goal.

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.