Gastrointestinal Cancer

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.

In the current issue of ONCOLOGYDrs. Bendell and Ryan have provideda valuable review of analcancer. They describe the dramaticeffect of multimodality therapy onthe quality of life and survival ofanal cancer patients. Currently, themajority of patients enjoy long-termsurvival without requiring major surgeryor a stoma. At Memorial Sloan-Kettering Cancer Center, we basetreatment recommendations on stageat presentation and the presence ofcomorbid disease.

Anal cancer accounts for 1.5% of digestive system malignancies inthe United States. In the past 30 years, substantial progress has beenmade in understanding the pathophysiology and treatment of thedisease. Anal cancer was once believed to be caused by chronic localinflammation of the perianal area, and treatment was abdominoperinealresection. From epidemiologic and clinical studies, we nowknow that the development of anal cancer is associated with humanpapillomavirus infection and that the disease has a pathophysiologysimilar to that of cervical cancer. Less invasive treatments have alsobeen developed, and the majority of patients with anal cancer can nowbe cured with preservation of the anal sphincter using concurrentexternal-beam radiation therapy and fluorouracil (5-FU)/mitomycin(Mutamycin) chemotherapy. Current areas under investigation includethe incorporation of platinum agents into the chemotherapyregimen and the use of cytologic screening studies for high-riskpopulations.

The article by Drs. Bendell andRyan reviews the associationbetween anal cancer and humanpapillomavirus (HPV) infectionand discusses current managementstrategies for patients with squamouscell carcinoma of the anal canal. Theauthors should be complimented ona thorough review of the literature,which supports that association andthe use of chemoradiation as the goldstandard for treatment of this groupof patients.

DUBLIN, California-Super-Gen Inc. has begun submission of a New Drug Application (NDA) for Orathecin, an oral camptothecin, for the treatment of pancreatic cancer patients who are refractory/resistant to available therapies. The submission will occur on a rolling basis and is ex-pected to be completed by the end of the first quarter of 2003. The submission will contain data on more than 2,700 patients treated under Orathecin study protocols, the company said in a news release.

NEW YORK-Total mesorectal excision (TME) has reduced the risk of local recurrence in rectal cancer, but adjuvant therapy is still needed in node-positive cases, according to Bruce Minsky, MD, vice chairman of radiation oncology at Memorial Sloan-Kettering Cancer Center in New York.

NANTES, France-European researchers are moving beyond colorectal cancer regimens based on infusional fluorouracil (5-FU) to comparing combinations and to examining the effects of scheduling on response and time to progression, according to Jean-Yves Douillard, MD, PhD. Professor Douillard, who developed a widely-used regimen for colorectal cancer, is professor of medical oncology and head of the department of medical oncology, Centre Rene Gauducheau, at the University of Nantes in France.

BALTIMORE-Between 11,000 and 12,000 colorectal cancer patients present with liver metastases each year. Surgical resection is ideal but does not remove microscopic metastases and disease left behind after surgery. "Today, treatment should start with neoadjuvant therapy in all colorectal cancer patients that have liver metastases," Yehuda Z. Patt, MD, said.

GLASGOW, Scotland-"Development of capecitabine (Xeloda) was inspired by the fact that what is wanted is an oral tablet that will mimic infusional fluorouracil (5-FU) and will have tumor-selective activation. Clearly, about 90% of patients prefer oral therapy, but they do not want to sacrifice efficacy for convenience," Christopher Twelves, MD, stated. A number of recent clinical trials suggest that capecitabine might be a simpler substitute for 5-FU in colorectal cancer regimens and Dr. Twelves, a consultant in medical oncology at Cancer Research UK, Glasgow, Scotland, discussed this possibility at the First International Colorectal Cancer Congress in Palm Beach, Florida.

HOUSTON-Preoperative chemoradiation and aggressive surgery produced good local disease control and sphincter preservation in patients with locally advanced rectal cancer treated at the University of Texas M.D. Anderson Cancer Center, Houston, but more effective systemic therapy is needed, according to Christopher H. Crane, MD. Dr. Crane, who is assistant professor of radiation oncology at M.D. Anderson, reviewed data from 392 patients with stage II or stage III rectal cancer treated there over the past decade.

NASHVILLE, Tennessee-Regimens that contain oxaliplatin (Eloxatin) as well as irintoecan (CPT-11, Camptosar) and fluorouracil (5-FU)/ leucovorin have produced prolonged survival of 18 to 21 months in patients with advanced colorectal cancer and should be considered for first-line therapy, according to Mace L. Rothenberg, MD. Dr. Rothenberg, who is professor of medicine at Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, reviewed the current status of oxaliplatin-based regimens.

SEATTLE-Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin lowers the relative risk of colorectal cancer by an overall rate of 24%, according to a study presented at the 67th Annual Scientific Meeting of the American College of Gastroenterology (abstract 12). The rate rises to 32% when aspirin/NSAIDs are used for more than 2 years.

TAEJON, Korea-In a study from Korea of patients with locally advanced rectal cancer, preoperative capecitabine (Xeloda) with leucovorin given concurrently with radiotherapy resulted in primary tumor downstaging and nodal downstaging, reported Jun-Sang Kim, MD, of Chungnam National University, Taejon, and colleagues.

SEATTLE-Having at least one follow-up colonoscopy within 5 years of a diagnosis of nonmetastatic colorectal cancer decreased the mortality risk by 40%, according to a study presented at the 67th Annual Scientific Meeting of the American College of Gastroenterology (president’s plenary session abstract 11).

Drs. Konner and O’Reilly have provided a thorough review of current perspectives on pancreatic cancer. The disease is lethal, difficult to diagnose in its early stages, and resistant to standard chemotherapy regimens. Surgery can be curative if performed when the tumor is small (< 2 cm), but only a minority of patients have small tumors.

The review by Drs. Konner and O’Reilly addresses a number of important issues in pancreatic cancer. Adenocarcinoma of the pancreas is a devastating disease,[1] not only because it will occur in approximately 30,000 Americans this year, and perhaps 200,000 people worldwide, but also because of its high associated mortality. Pancreatic adenocarcinoma is one of the least treatable and, therefore, most lethal of all cancers. Fully 95% of all patients with an established diagnosis of adenocarcinoma of the pancreas will die of their disease.

Pancreatic cancer is a leading cause of cancer-related mortality. Treatment has limited efficacy, and 5-year survival rates remain less than 5%. Insights from epidemiology and discoveries in molecular genetics have laid

ORLANDO-In a randomized multicenter phase II study of advanced pancreatic carcinoma by the European Organization for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Group, the combination of docetaxel (Taxotere) and gemcitabine (Gemzar) was "promising" relative to docetaxel/cisplatin (Platinol), Manfred P. Lutz, MD, of University Hospital, Ulm, Germany, said at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 498).

Radiation therapy alone is an adequate treatment for some patients with rectal cancer, according to a study published in a recent issue of the International Journal of Radiation Oncology, Biology, Physics (54:142-149, 2002).

KING OF PRUSSIA, Pennsylvania-Protarga, Inc. has received comments from the FDA that allow it to proceed with two separate phase III clinical studies of its new cancer drug Taxoprexin Injection (DHA-pacli-taxel) for the treatment of metastatic melanoma and pancreatic cancer. Taxoprexin is made by linking the fatty acid docosahexaenoic acid (DHA) to paclitaxel, the company said in a news release.

ORLANDO-One in four patients with resected rectal cancer who later underwent surgical salvage for recurrence at a single site were still alive at 5 years, according to a subanalysis of a large, randomized Intergroup study presented at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 507). "Approximately 27% of the patients have long-term survival and appear to be cured," said Michael J. O’Connell, MD, director, Allegheny Cancer Center, Allegheny General Hospital, Pittsburgh.

The US Senate Health, Education, Labor, and Pensions Committee has passed the Eliminate Colorectal Cancer Act (S.710), legislation introduced by Sen. Jesse Helms (R-NC) and Sen. Edward M. Kennedy (D-Mass). The bill, with the companion

ORLANDO-A phase III clinical trial of first-line therapy in advanced colorectal cancer showed improved progression-free survival (PFS) for weekly infusional FUFOX-fluorouracil/folinic acid (5-FU/FA)/oxaliplatin (Eloxatin)-compared with the Mayo bolus 5-FU/FA (leucovorin in the United States) regimen, Axel Grothey, MD, University of Halle, Halle, Germany, said at the American Society of Clinical Oncology 38th Annual Meeting (abstract 512).

ORLANDO-Delivering Selective Internal Radiation Therapy (SIRT) via radioactive microspheres (SIR-Spheres) significantly increased response to treatment and time to progression in a small cohort of patients receiving chemotherapy for advanced colorectal cancer liver metastases.

ORLANDO-Treatment of unre-sectable hepatocellular carcinoma (HCC) with 90-yttrium-embedded glass micro-spheres (TheraSphere, MDS Nordion) appears to be safe, effective, and less toxic than the alternative, transarterial che-moembolization (TACE).