ONCOLOGY Vol 19 No 3

Dr. Colasanto and his associatesare to be commended forskillfully and comprehensivelyreviewing the issues concerning theprovision of nutritional support to patientsundergoing radiation therapy.Their recommendations are well supportedby review of scientific studies,and the article is written in such a wayas to be accessible to those not fullyversed in prescribing nutritional support.There remain a few points thatdeserve discussion.

The most effective form of therapyfor muscle-invasive bladdercancer is radical surgery andurinary diversion. Numerous clinicalseries demonstrate stage-for-stage 5-and 10-year survival data that are betterthan that seen for other treatmentmodalities.[1] The widespread applicationof continent urinary diversionover the past 2 decades has furtheredthe acceptance of radical surgery, asit provides for the lost function ofvolitional storage and emptying ofurine. Even patients who undergo astandard ileal loop diversion generallytolerate it well and adapt to thealtered body image.[2]

Pisters and colleagues from theM. D. Anderson Cancer Centeroffer a state-of-the-art discussionof the staging and treatment ofpancreatic cancer. Their treatise addressesmost of the current issues ofcontroversy surrounding this diseasefrom a largely nonparochial standpoint,and should serve as a primerfor the multidisciplinary approach tothe treatment of pancreatic ductal cancer.Their call for and justification ofregionalization of treatment in patientswith potentially resectable diseaserings true with virtually all nationaland international studies that have examinedthis topic from the aspect ofmorbidity, mortality (and thus survival),duration of hospitalization, andof course in our current economic climate,cost.[1-7] This topic should nolonger be considered controversial.

What do we know for sureabout the health implicationsof inappropriateweight and nutrition? We know thatapproximately 60% of US adults currentlyare considered overweight orobese[1] and approximately 300,000deaths a year in this country are associatedwith overweight and obesity.And, most importantly for this discussion,we know that randomizedcontrolled trials suggest that lifestylechanges resulting in the loss of excessweight reduce the risk cardiovasculardisease, lower blood pressure, lowerblood sugar, and improve lipid levels.[2] In essence, there is a chain ofevidence: A medical condition exists,the condition causes adverse outcomes,with interventions the conditioncan be reversed, and the problemsit causes can be ameliorated.

Recent advances in understandingthe cellular mechanismsthat determine tumor developmentand progression havespawned a plethora of the so-called“smart therapies”-targeting variousaspects of aberrant cell signaling.Some of the most promising of theseinclude agents targeting tumor angiogenesis,among them the vascularendothelial growth factor (VEGF)-specific humanized monoclonal antibodybevacizumab (Avastin), whichis the most advanced antiangiogenicagent in clinical development. Theinitial promise of this agent is nowsupported by proof-of-concept clinicaldata and is discussed in the comprehensivereview by Olszewski andcolleagues. But the question remains:How does bevacizumab achieve thisclinical benefit?

Drs. Fernando and Sandler havewritten a thorough review thathas documented why a bladder-conserving therapy can now bemore widely accepted treatment for patientswith muscle-invading bladdercancer. They have shown that this treatmentapproach, while selective, doeshave a high likelihood of eradicatingthe primary tumor, preserving good organfunction, and not compromisingpatient survival. These successful approacheshave evolved over the past 25years following initial reports of theeffectiveness of cisplatin against transitionalcell carcinoma and then reportsof added efficacy when cisplatinis given concurrently with radiation.

Although in centers where pancreatectomy is performed frequently,associated morbidity and mortality rates have improved, long-term outcomesin pancreatic adenocarcinoma patients remain poor when surgeryis the sole therapeutic modality. The impact of adjuvant chemotherapyon survival in patients with localized pancreatic cancer remainsincompletely defined. The European Study Group for Pancreatic Cancer(ESPAC)-1 trial has suggested that overall survival rates are superiorwhen chemotherapy is added to surgery, even when regimens believedto be relatively ineffective in the treatment of advanced diseaseare used. The role of radiotherapy given with chemotherapy is alsounresolved, but chemoradiation continues to receive consideration inthe multimodality approach to localized pancreatic cancer. Enhancedcollaboration and increased involvement by pancreatic surgeons havehelped in the recruitment of pancreatic cancer patients for large-scalerandomized clinical trials in Europe and the United States. Many newerchemotherapeutic agents with efficacy in gastrointestinal cancers haveyet to be investigated in the adjuvant and neoadjuvant settings.

This is a timely review on thecurrent status of selective bladderpreservation for muscleinvasivebladder cancer. Although controversial,the concept is extremely attractiveto patients, and evidence fromretrospective and/or small series demonstrateits efficacy. Most of these trials,however, have included highlyselected patients. Unfortunately, thereare few, if any, ongoing randomizedcontrolled trials comparing radical cystectomyto bladder-preserving protocols.Although the overall 5-yearsurvival rate for radical cystectomy andtrimodality therapy is approximately50%, patients with pure T2 disease frequentlyachieve 5-year survival ratesapproaching 70%.[1-3] While it is clearlybeyond the scope of this editorial togo into an in-depth analysis of all thestudies reported to date, several significantquestions remain.

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.

Malnutrition plays a key role in the morbidity of head and neckcancer patients receiving surgery, chemotherapy, radiotherapy, or combined-modality therapy. In addition to weight lost prior to the diagnosisof head and neck cancer, the patient may lose an additional 10% ofpretherapy body weight during radiotherapy or combined-modality treatment.A reduction of greater than 20% of total body weight results inan increase in toxicity and mortality. Severe toxicity can result in prolongedtreatment time, which has been implicated in poor clinical outcome.Early intervention with nutritional supplementation can reducethe chance of inferior outcome in patients at high risk of weight loss.The preferred route of nutritional support for these patients is enteralnutrition. Two commonly used methods for enteral feedings arenasoenteric and percutaneous endoscopic gastrostomy. It is importantto take into account the ethical considerations involved in providinglong-term nutritional support, particularly for patients with terminalconditions. Nutritional directives are best evaluated throughmultidisciplinary efforts, including input from the patient as well asmembers of the nursing, nutritionist, and medical staff.

While organ preservation with nonextirpative surgery, radiotherapy,and frequently, chemotherapy has become a favored strategy in thetreatment of many cancers, bladder preservation for patients with invasivedisease remains controversial. The standard treatment for muscleinvasivebladder cancer in the United States is still radical cystectomywith pelvic lymph node dissection. An alternative to cystectomy ismultimodality bladder preservation with thorough transurethral resection,chemotherapy, and radiation therapy. This review will addressissues raised by a multimodality approach for the treatment of invasivebladder cancer.

Drs. Pisters, Wolff, Crane, andEvans have provided an excellentoverview of contemporaryapproaches to staging, surgicalmanagement, and treatment ofpatients with potentially resectablepancreatic cancer. Given the impressiveadvances in our understandingof the biology and genetics of pancreaticcancer, we would agree thatcurrent opportunities for progressagainst this malignancy are encouraging.The reality, however, is thatmortality rates still exceed 95%.While the article addresses the clinicalmanagement of patients with operablepancreatic cancer, this subsetof patients constitutes only 10% to15% of all patients with the disease.This group as well as patients withlocally advanced and metastatic diseaseare in need of new and innovativetreatment strategies. In thisreview, we will highlight several ofthe points made by the authors.

Perhaps no other group of malignanciesis more severely affectedby the problems patients havewith establishing or maintaining goodnutrition than those of the upper aerodigestivetract. Nutrition, or malnutrition,is a critical considerationduring all phases of the diagnosis, treatment,and long-term management ofpatients with head and neck malignancies, even following curative therapy.

In this issue of ONCOLOGY, Olszewski,Grossbard, and Kozuchprovide an excellent overview ofthe role of antiangiogenic therapy inthe treatment of patients with metastaticcolorectal cancer. The authorshave brought several important issuesto the forefront that warrant furtherdiscussion, and these issues will beaddressed in this commentary.

Olszewski and colleagues reviewpreclinical and clinicaldata regarding vascular endothelialgrowth factor (VEGF) inhibitors,with particular attention to thedevelopment of bevacizumab (Avastin)in patients with colorectal cancer.The translation from biologic conceptto clinical proof of concept has beenstriking in its rapidity. However, manyimportant questions remain, and thisstory is only beginning to unfold. Inthis commentary, we will highlightsome of those questions that bear onthe optimal use of VEGF inhibitors inpatients with colorectal cancer.