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The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

Radical prostatectomy and ultrasound-guided transperinealbrachytherapy are both acceptedtreatment options for men with clinicallylocalized prostate cancer.Investigators continue to argue overthe relative effectiveness of each ofthese procedures, not only from thestandpoint of cure, but also with regardto how each treatment affectsquality of life. With the recent closureof a prospective, randomized trial addressingthese issues (the SurgicalProstatectomy Interstitial RadiationIntervention Trial, or SPIRIT) due tolack of patient accrual, it is unlikelythat a direct comparison of these techniqueswill be performed in the foreseeablefuture.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

Radical prostatectomy and ultrasound-guided transperinealbrachytherapy are both commonly used for the treatment of localizedprostate cancer. No randomized trials are available to compare thesemodalities. Therefore, the physician must rely on institutional reportsof results to determine which therapy is most effective. While some investigatorshave concluded that both therapies are effective, others haveconcluded that radical prostatectomy should remain the gold standardfor the treatment of this disease. This article reviews the major seriesavailable for both treatments and discusses the major controversiesinvolved in making these comparisons. The data indicate that for lowriskdisease, both treatments are effective, controlling disease in over80% of the cases, with no evidence to support the use of one treatmentover the other. Similarly, for intermediate-risk disease, the conclusionthat one treatment is superior to the other cannot be drawn. Brachytherapyshould be performed in conjunction with external-beam radiationtherapy in this group of patients. For patients with high-risk disease,neither treatment consistently achieves biochemical control rates above50%. Although radical prostatectomy and/or brachytherapy may playa role in the care of high-risk patients in the future, external-beamradiation therapy in combination with androgen deprivation has thebest track record to date.

Melanoma incidence and mortality continue to rise unabated in older individuals. Early clinical detection should take into account the different subtypes.

Dr. Kozuch and coauthors havewritten a comprehensive reviewof gallbladder and biliarytract carcinoma. We would like to updateseveral issues related to this topic,with particular emphasis on new chemotherapystrategies and drug combinationsfor improving outcomes.

Cancers of the gallbladder andbile ducts are uncommon, aggressivemalignancies thatpresent both a diagnostic and therapeuticchallenge. With an annual incidenceof 7,200 cases in the UnitedStates, and the difficulty in diagnosingbiliary tract tumors, there is a paucityof data supporting therapeuticoptions. This comprehensive updateby Daines et al demonstrates the advancesin diagnostic and staging techniques,which have led to appropriatesurgical resection. Despite these advances,the prognosis of gallbladderand cholangiocarcinoma remains bleak,without significant improvement in survival,contrary to the author's optimisticintroduction. There is a lack of activechemotherapy and clinical trials exploringadjuvant and palliative therapy.Guidelines such as those advocated bythe National Comprehensive CancerNetwork (NCCN) help to establish standardsfor the evaluation and treatmentof these uncommon tumors and providea framework for the developmentof clinical trials.[1]

Gallbladder carcinoma and carcinoma of the bile ducts are relativelyrare cancers in the United States. These cancers are often diagnosedin an advanced stage due to their nonspecific symptomatologyand until recently have been associated with a dismal prognosis. Recentadvances in imaging and surgical techniques along with emergingoptions in palliative chemotherapy have improved the outlook inthese cancers. While complete surgical resection remains the only hopeof cure in both these cancers, palliative biliary decompression and chemotherapyresult in substantial improvement in quality of life. Part 1 ofthis review, which appeared in last month’s issue, provided a relevantand comprehensive update of molecular pathology, imaging modalities,and surgical care. In part 2, we examine palliative care and systemictherapy in gallbladder and biliary tract carcinomas, as well asthe use of liver transplantation in the treatment of cholangiocarcinomas.These strategies are of relevance to internists as well as oncologistscaring for these patients.

Data from adjuvant trials clearly indicate that one of the most importantproblems in patients with resected non-small-cell lung cancer(NSCLC) is compliance to chemotherapy. In the postoperative setting,significant comorbidities and incomplete recovery after surgery oftenmake it difficult for patients to tolerate or comply with systemic therapy.Therefore, it may be preferable to deliver chemotherapy before surgeryas "neoadjuvant" or "induction" chemotherapy. The rationale for usinginduction chemotherapy is based on evidence that chemotherapymight reduce tumor burden and possess activity againstmicrometastases, resulting in improved results by surgery, radiotherapy,or a combination. Moreover, induction therapy facilitates in vivo assessmentof tumor response or resistance. Potential drawbacks includethe risk of perioperative complications, and the possibility that the tumormass may become unresectable due to disease progression. Duringthe past decade, four phase III randomized trials evaluated the roleof induction chemotherapy in stage IIIA NSCLC. The first three studiesconsistently showed that induction chemotherapy improves survivalcompared with surgery alone. More recently, a large phase III trialperformed by French investigators suggested a survival benefit in stageI/II patients, but not stage IIIA. The high activity of new platinumbasedchemotherapy-based on response rate and 1-year survival inadvanced disease-reinforces the rationale for the use of these newcombinations in early-stage NSCLC, especially for a subset of patientstraditionally treated with surgery alone. Several phase III trials arecurrently evaluating the role of new doublets as induction chemotherapy;these are discussed in the article. The results of these ongoingphase III trials should help clarify the role of induction chemotherapyin early-stage disease.

SAN DIEGO-Three multicenter phase II trials in the United States, Canada, and Europe, representing the pivotal trials that led to approval of gemtuzumab ozogamicin (Mylotarg), were updated at the 45th Annual Meeting of the American Society of Hematology (abstract 615), looking only at patients age 60 and over. Richard A. Larson, MD, professor of medicine, University of Chicago, presented the results of the largest series of older patients with acute myeloid leukemia (AML) in first relapse who have been treated with gemtuzumab.

Virtually every management decisionrelated to prostate canceris highly controversial.Should we screen men for prostatecancer with prostate-specific antigen(PSA)? If so, what are the proper cutoffvalues? If we detect an early prostatecancer, is treatment warranted? Ifwe find an aggressive cancer, is treatmenteffective? If treatment is deemedwarranted, what is the optimal managementstrategy (radical prostatectomyvs radiation therapy)? If radicalprostatectomy is selected, should theprocedure be performed roboticallyor via an open approach? If radiationtherapy is selected, does eitherbrachytherapy or external-beamirradiation offer an advantage? Isthere a role for neoadjuvant hormonaltherapy in men undergoing definitiveintervention?

Gallbladder carcinoma and carcinoma of the bile ducts are relativelyrare cancers in the United States. These cancers are often diagnosedin an advanced stage due to their nonspecific symptomatologyand until recently have been associated with a dismal prognosis. Recentadvances in imaging and surgical techniques along with emergingoptions in palliative chemotherapy have improved the outlook inthese cancers. While complete surgical resection remains the only hopeof cure in both these cancers, palliative biliary decompression and chemotherapyresult in substantial improvement in quality of life. Part 1 ofthis review provides a relevant and comprehensive update of molecularpathology, imaging modalities, and surgical care. In part 2, which willappear next month, we will review palliative care and systemic therapyin gallbladder and biliary tract carcinomas, as well as the use of livertransplantation in the treatment of cholangiocarcinomas. These strategiesare of relevance to internists as well as oncologists caring forthese patients.

Screening for prostate cancer by determining serum prostate-specificantigen (PSA) levels has resulted in a stage migration such thatpatients with high-risk disease are more likely to be candidates for curativelocal therapy. By combining serum PSA, clinical stage, and biopsyinformation-both Gleason score and volume of tumor in the biopsycores-specimen pathologic stage and patient biochemical disease-freesurvival can be estimated. This information can help patients and cliniciansunderstand the severity of disease and the need for multimodaltherapy, often in the context of a clinical trial. While the mainstays oftreatment for local disease control are radical prostatectomy and radiationtherapy, systemic therapy must be considered as well. A randomizedtrial has shown a survival benefit for radical prostatectomy inpatients with positive lymph nodes who undergo immediate adjuvantandrogen deprivation. Clinical trials are needed to clarify whether adjuvantradiation therapy after surgery confers a survival benefit. PSAis a sensitive marker for follow-up after local treatment and has proventhat conventional external-beam irradiation alone is inadequate treatmentfor high-risk disease. Fortunately, the technology of radiationdelivery has been dramatically improved with tools such as three-dimensionalconformal radiation, intensity-modulated radiation therapy,and high-dose-rate brachytherapy. The further contributions of pelvicirradiation and neoadjuvant, concurrent, and adjuvant androgen deprivationtherapy have been defined in clinical trials. Future managementof high-risk prostate cancer may be expanded by clinical trialsevaluating neoadjuvant and/or adjuvant chemotherapy in combinationwith androgen deprivation.

The introduction of prostate-specific antigen (PSA) as a reliabletumor marker for prostate cancer brought significant changes in theend points used for outcome reporting after therapy. With regard to adefinition of failure after radiation, a consensus was reached in 1996that took into account the particular issues of an intact prostate aftertherapy. Over the next several years, the consensus definition issued bythe American Society for Therapeutic Radiology and Oncology(ASTRO) was used and studied. Concerns and criticisms were raised.The sensitivity and specificity of this definition vs other proposals hasbeen investigated, and differences in outcome analyzed and compared.Although the ASTRO definition came from analysis of datasets on external-beam radiation and most of the work on this topic has been withthis modality, failure definitions for brachytherapy must be exploredas well. The concept of a universal definition of failure that might beapplied to multiple modalities, including surgery, should also be investigated,at least for comparative study and research purposes.

AN ANTONIO-Breast cancer patients with BRCA 1 or 2 mutations undergoing breast-conserving surgery plus radiotherapy do not have more in-breast recurrences or radiotherapy complications than their counterparts without the germ-line mutation, and they derive particular benefits from prophylactic bilateral oophorectomy, according to 10-year results from a large collaborative database reported at the 26th San Antonio Breast Cancer Symposium (abstract 5).

Over the past decade, remarkable advanceshave been made in the biology and treatmentof multiple myeloma.[1] In most, if not all,patients, myeloma evolves from a precursorstage called monoclonal gammopathy of undeterminedsignificance (MGUS); MGUS isasymptomatic, but progresses to myeloma ora related disorder at a rate of 1% per year.[2]Although precise pathogenetic mechanismsremain elusive, recent studies show that aprimary translocation, usually involvingthe immunoglobulin heavy chain locus onchromosome 14q32, or in some cases theimmunoglobulin lambda light chain locus,can be detected at the MGUS stage in 60-65% of individuals.[3] Progression of MGUSto myeloma appears to be a random eventoften accompanied by secondary translocations(eg, c-myc), mutations in RAS or othergenes, as well as changes in the microenvironmentincluding the induction of angiogenesis.

The role of prostate brachytherapyin the treatment of prostatecancer continues to expand andevolve. The increasing clinical use andwider acceptance of this treatmentmodality can be attributed to published10-year data demonstrating cure ratesequivalent to those of radical prostatectomyand to quality-of-life studiesthat demonstrate relatively lowermorbidity from brachytherapy comparedto surgery.[1-4] It is the easeand convenience of treatment, the apparentequivalent cure rates, and theperception of lower morbidity thatmakes this treatment so appealing topatients. However, like all treatments,prostate brachytherapy does have sideeffects, and some patients will suffersignificant complications or severemorbidity.

Drs. Merrick, Wallner, and Butlerhave compiled informationregarding patient selection forprostate brachytherapy[1] and concludethat, “While there is no shortageof opinions regarding symptomsor circumstances that render the useof brachytherapy inadvisable, most arebaseless.” They go on to say that,“Reports to date have failed to establishany firm contraindication.” I amimpressed with the certainty such astatement projects for a disease as heterogeneousas prostate cancer.

Following permanent prostatebrachytherapy with or withoutsupplemental external-beamradiation therapy, encouraging longtermbiochemical outcomes-includinga morbidity profile that comparesfavorably with competing local modalities-have been reported forpatients with low-, intermediate-, andhigh-risk features.[1,2] The efficacyand morbidity of prostate brachytherapyare dependent on implantquality. Substantial differences havebeen reported in the incidence andclinical course of brachytherapyrelatedmorbidities, with many of theconflicts likely related to patientselection, technical differences intreatment planning, intraoperativetechnique, or variation in patient managementphilosophies.[3-6]

The myriad effects of androgendeprivation therapy (ADT) inmen were really not appreciateduntil those without metastatic prostatecancer received such treatment.For example, fatigue-now recognizedas a common toxicity of ADT-was once more likely attributed tometastatic disease. Today, however,patients who are otherwise fully functional,healthy, and asymptomatic arebeing treated for a rising prostate-specificantigen level after primary therapy.In these men, the side effects ofADT can be very dramatic and aremore clearly related to the initiationof therapy.

For the past 60 years, the treatmentof advanced prostate cancerhas consisted of deprivingcancer cells of androgens.[1] The keypremise of androgen ablation is thatmost prostate carcinoma cell growthis initially androgen-dependent. Theandrogen receptor expressed by thesecells binds dihydrotestosterone, whichis then transported into the nucleus,leading to a cascade of events thatinduce cellular growth. If androgen isremoved, cellular death ensues via apoptosisof the androgen-sensitive cells.

Androgen deprivation, as a form of treatment for prostate cancer,has been used for decades. Within the last decade, however, its use hasincreased significantly. Therefore, it is incumbent upon the physicianto be familiar with the side effects associated with this treatment. Someof these side effects (eg, osteoporosis, changes in lipid profiles, andanemia) may be associated with significant morbidity, whereas others(eg, impotence, decreased libido, fatigue, and hot flashes) primarilyaffect the patient’s quality of life. Prevention strategies and treatmentsexist for many of these side effects. In addition, alternative forms ofantiandrogen therapy such as intermittent hormone ablation andantiandrogen monotherapy may be effective, with the added benefit ofminimizing side effects. This review focuses on the wide range of sideeffects associated with androgen ablation as well as preventive and treatmentstrategies.

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.