ONCOLOGY Vol 18 No 11

This excellent and practical articleby Dr. Ravdin is worthwhilereading for every physician involvedin the long-term care of womenwith a previous diagnosis of breastcancer. Dr. Ravdin clearly outlinesthe theoretical rationale underlying theincreased risk of osteopenia and osteoporosisin women with a history ofbreast cancer. The fact that such womencommonly undergo prematuremenopause either deliberately, as partof treatment for breast cancer, or as asecondary effect of chemotherapy, andthat estrogen-replacement therapywith or without progesterone remainscontraindicated for fear of increasingthe risk of recurrence, clearly contributesto the increased possibility ofdeveloping osteopenia or osteoporosis.New data supporting the role ofaromatase inhibitors in adjuvant therapy[

The authors present a comprehensivereview of anthracycline-based adjuvant chemotherapyregimens, supporting the useof these regimens over CMF (cyclophosphamide[Cytoxan, Neosar],methotrexate, fluorouracil [5-FU]) inearly-stage breast cancer. They concludethat the addition of taxanes toanthracycline-containing regimens innode-positive disease may conferadditional benefit. Newer regimenscontaining taxanes and other agentsthat omit the use of anthracyclinesshow promise but are still underinvestigation.

The results of treatment for metastatic melanoma remain disappointing.Single-agent chemotherapy produces response rates ranging from8% to 15%, and combination chemotherapy, from 10% to 30%. However,these responses are usually not durable. Immunotherapy, particularlyhigh-dose interleukin (IL)-2 (Proleukin), has also shown a lowresponse rate of approximately 15%, although it is often long-lasting.In fact, a small but finite cure rate of about 5% has been reported withhigh-dose IL-2. Phase II studies of the combination of cisplatin-basedchemotherapy with IL-2 and interferon-alfa, referred to as biochemotherapy,have shown overall response rates ranging from 40% to60%, with durable complete remissions in approximately 8% to 10% ofpatients. Although the results of the phase II single-institution studieswere encouraging, phase III multicenter studies have reported conflictingresults, which overall have been predominantly negative. Variousfactors probably explain these discrepancies including differentbiochemotherapy regimens, patient selection, and, most importantly,“physician selection.” Novel strategies are clearly needed, and the mostencouraging ones for the near future include high-dose IL-2 in combinationwith adoptive transfer of selected tumor-reactive T cells afternonmyeloablative regimens, BRAF inhibitors in combination with chemotherapy,and the combination of chemotherapeutic agents andbiochemotherapy with oblimersen sodium (Genasense).

Dr. Buzaid’s article, “Managementof Metastatic CutaneousMelanoma,” is a review ofavailable treatment options with a historicalperspective. The conclusion includesa recommendation for the useof aggressive combination therapy inpatients who are young and otherwisehealthy enough to tolerate the toxicitiesof these aggressive forms of therapy,and consideration of single-agenttherapy for those who cannot tolerateaggressive combination regimens.While this review article includes thepublished reports as of the time of itssubmission, there are additional agentsand regimens that warrant mentiondue to their likelihood of improvingthe treatment landscape for future patientswith this devastating disease.Furthermore, some of the promisingregimens mentioned in this reviewshould be more closely scrutinized.The following commentary will coverthe topics included in Dr. Buzaid’sreport as well as updates on the currentstatus and future of selected investigationalagents.

The article by Song, Kavanagh,Benedict, and Schefter is an insightfuland interesting summaryof this new technologic approachto the treatment of extracranial tumors.The work summarizes thesalient aspects of the emerging stereotacticbody radiation therapy (SBRT)paradigm, and characterizes the rationale,methodologies, and perceivedpotential for this promising new approachto treatment. The authorspresent interesting perspectives on thechallenges facing early adopters ofthe approach and, as early adopters,we find that our own experience supportsmany of the conclusions drawnby the authors.

Although chemotherapy regimenscan produce objectiveresponses in patients withmetastatic melanoma, curative responsesare extremely rare. It is thereforeof significant interest that themajority of complete responses to immunotherapywith high-dose interleukin(IL)-2 (Proleukin) alone aredurable and probably curative.[1]

Song and colleagues deliver athorough and fair review of theinitial clinical investigations ofa new paradigm in radiotherapy mostrecently called stereotactic body radiationtherapy (SBRT).[1] Oncology observers may take exception withthe use of the designation “new paradigm.”After all, from a tumor controlpoint of view, skeptics might say,“radiotherapy is radiotherapy.” Recentadvances in radiotherapeutictechnology such as three-dimensionsal(3D) conformal therapy and intensity-modulated radiotherapy (IMRT)have made treatments less toxic, butnot particularly more effective in curingcancer.

Estrogen is known to play an important role in skeletal health. Femalebreast cancer patients who receive treatments that reduce estrogenlevels, such as aromatase inhibitors, may increase their risk of developingosteoporosis and their risk of fracture. Clinical guidelinesenable the physician to assess the risk of osteoporosis by patient historyand physical examination. For patients identified as being at risk, it isnecessary to test bone mineral density (BMD), using the result to determinewhich patients require treatment. Two groups can be identified asrequiring BMD assessment according to general guidelines: patients< 45 years old who become menopausal due to treatment, and breastcancer patients receiving aromatase inhibitors. Bisphosphonates appearto be the logical treatment of choice for breast cancer patients, asthey do not interact with the estrogen receptor. Although not all womenreceiving aromatase inhibitors will require additional treatment for bonehealth, postmenopausal women with a history of breast cancer at riskof osteoporosis should be identified, monitored, and managed accordingto practice guidelines.

Stereotatic body radiation therapy (SBRT) is a rapidly evolving cancertreatment method in which concepts and techniques previously developedfor brain tumor radiosurgery are adapted to eradicate tumorselsewhere in the body. The spatial accuracy, conformality, and steepradiation dose gradients of radiosurgery, which have been critical to itssuccess in the treatment of intracranial tumors, are applied in SBRT totreat a variety of extracranial tumors. Early results demonstrate excellentresponse rates and low toxicity with a variety of hypofractionateddose regimens and localization/immobilization techniques. This articleprovides an overview of the rationale and results of SBRT for specificindications, descriptions of some methods of treatment delivery, anddiscussion of potential areas of future investigation.

The treatment of breast cancer has progressed substantially overthe past 15 years. Data from randomized adjuvant trials have shownthat the risk of disease recurrence and death is significantly reducedwhen adjuvant chemotherapy and/or hormonal therapy is added to treatment.As new strategies are incorporated, one of the continued controversiesin patient management is whether adjuvant anthracyclinesshould be the preferred treatment for all patients. Data from randomizedand translational clinical trials have become available and arehelping to elucidate the proper role of anthracyclines, as well as their acuteand long-term toxicities. In most situations, an anthracycline is currentlypreferred, but other single and combination chemotherapies arecurrently under evaluation and appear promising for use in the adjuvantsetting. Continued breast cancer research using molecular markers(such as topoisomerase II–alpha and gene clusters) as predictors oftreatment response, could help individualize decisions regardingwhether to incorporate anthracyclines into adjuvant therapy regimens.

Only a minority of elderly patientswith advanced non–small-cell lung cancer(NSCLC) have been offered palliativechemotherapy, as indicated by clinicalsurveys beginning in the 1980s.Lilenbaum’s thorough review of thetreatment of locally advanced and metastaticNSCLC studies in two specialpopulations (elderly and Eastern CooperativeOncology Group [ECOG]performance status [PS] 2 patients)highlights a new trend seen with theadvent of better-tolerated chemotherapyregimens.

Lilenbaum’s paper highlightingrecent controversies in the managementof advanced non–small-cell lung cancer (NSCLC) inthe elderly and in vulnerable performancestatus (PS) populations is bothtimely and relevant. A recent Surveillance,Epidemiology and End Results(SEER) analysis suggests that nearly50% of all patients diagnosed withNSCLC are 70 years of age or older.Non–small-cell lung cancer generallypeaks in incidence in the elderly, andthe population of the United States iscontinually aging, with nearly 20%expected to be over age 65 by theyear 2030.[1]