Michael L. Grossbard, MD

Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma characterized by distinct and unique pathological, molecular, radiographic, and clinical features. While the incidence of pure BAC is rare, comprising only 1% to 4% of non–small-cell lung cancer (NSCLC), mixed subtypes (including BAC with focal invasion and adenocarcinoma with BAC features) represent as much as 20% of adenocarcinomas-and that figure may be increasing. Despite the longstanding recognition of this entity, there is no established treatment paradigm for patients with multifocal BAC, resulting in competing approaches and treatment controversies. Current options for multifocal BAC include both surgery and systemic therapies. Unfortunately, prospective data on systemic approaches are limited by study design and small patient numbers; there are only seven phase II studies involving four therapies. This article evaluates key characteristics of BAC, including the current understanding of histopathology and tumor biology. In addition, it comprehensively reviews the systemic phase II studies in an attempt to clarify the therapeutic challenges in this disease. It also includes the first proposed treatment paradigm that integrates both EGFR mutational status and the sub-histologies, mucinous and nonmucinous BAC.

Drs. Perez and Muss provide acomprehensive review of therole of adjuvant chemotherapyin the management of breast cancerpatients. The benefits of anthracyclinevs nonanthracycline regimens are discussed,the taxanes are reviewed indetail, and data regarding dose intensity,dose density, and optimal numberof chemotherapy cycles areexplored. Data on newer agents andbiologic agents also are presented.Debate continues regarding the subsetsof patients who will derive thegreatest benefit from chemotherapyand which regimen is most appropriate.While the review indicates theefficacy of several regimens as definedby randomized clinical trials, itdoes not emphasize patient-specificfactors in determining the optimaltherapy for a given patient.

Vascular endothelial growth factor (VEGF) plays a crucial role inthe growth and metastatic spread of cancer. Bevacizumab (Avastin) isthe first commercially available VEGF inhibitor, earning US Food andDrug Administration (FDA) approval in February 2004. In combinationwith fluorouracil (5-FU)-based chemotherapy, this agent significantlyprolongs overall and progression-free survival of patients withmetastatic colorectal cancer. This review details the emerging role ofthe drug, its unique side effects, and other practical considerations relatedto bevacizumab therapy. Ongoing trials attempting to define additionalindications for bevacizumab as well as the development ofother promising angiogenesis inhibitors are also reviewed.

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.

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.

Monoclonal antibodies (MoAbs) for cancer have been the subject of intense clinical investigation for nearly 2 decades.[1] Although the concept of MoAb therapy is simple, a host of unforeseen difficulties hindered the realization of clinical benefit from this therapeutic approach.