Gastrointestinal Cancer

Surgical resection offers the only potential cure for pancreatic adenocarcinoma. Unfortunately, while perioperative outcomes have improved dramatically in recent years, few patients present with tumors that are amenable to resection, and even after resection of apparently localized disease, long-term survival is poor.

Despite advances in endoscopic and other screening techniques, less than half of US adults at risk for colorectal cancer undergo adequate screening. As a consequence, approximately half of all new cases of colorectal cancer are diagnosed in later stages.

Sorafenib is indicated for the treatment of patients with advanced renal cell cancer, and patients with unresectable hepatocellular cancer. Sunitinib is indicated for the treatment of patients with advanced renal cell cancer, and patients with gastrointestinal stromal tumor (GIST) after disease progression on imatinib mesylate (Gleevec).

Researchers from the Leeds Institute of Molecular Medicine at the University of Leeds assessed the quality of colon cancer surgery and noted that there was marked variability in the plane of surgery achieved in colon cancer.

Gemcitabine (Gemzar)-based regimens have been the mainstay of front-line treatment for patients who present with advanced pancreatic cancer over the past decade, but most medical oncologists throw their hands up in frustration when considering what therapeutic options a patient is left with once he or she has progressed beyond first-line therapy. This is not without reason-as nicely summarized in the review article by Almhanna and Kim, studies in the published medical literature focusing on treatment of pancreatic cancer in the salvage setting have generally been small and have shown very modest clinical efficacy, characterized by low response rates and progression-free survival of a few months at best.

Pancreatic cancer is the fourth leading cause of cancer mortality in the United States. According the American Cancer Society, about 37,680 new cases are anticipated in the year 2008, and 34,290 patients will die from the disease.[1] This malignancy is a very aggressive tumor, and patients often present with advanced-stage disease. Surgical resection, when possible, provides the only opportunity for cure. Even with R0 resection, pancreatic cancer still carries an overall dismal prognosis, and therefore adjuvant treatment is offered.

CHICAGO-In the adjuvant treatment of colon cancer, addition of oxaliplatin (Eloxatin) to the FULV regimen is associated with a near-significant 15% relative reduction in the risk of death, according to results from a National Surgical Adjuvant Breast and Bowel Project trial (NSABP C-07).

The paper by Almhanna and Kim addresses a clinical dilemma in the treatment of pancreatic cancer, for which no standard currently exists. The review article concisely summarizes studies in the second-line setting that have been conducted to date, many of which have been published only in abstract form. The authors organize the studies into tables according to the number of agents in the trials and highlight the response rates and toxicities. The inclusion of study endpoints (both primary and secondary) would have made the tables more informative. In the article, the studies are organized according to the specific agent studied. Several of the studies continue to use gemcitabine (Gemzar) in combination with other agents in the second-line setting, but we have insufficient data to determine that continuing gemcitabine in this setting is worthwhile.

CHICAGO-Two new agents-an inhibitor of heat shock protein 90 and an inhibitor of insulin-like growth factor 1 receptor-appear promising for treating gastrointestinal stromal tumors that are resistant to available tyrosine kinase inhibitors, researchers said at ASCO 2008.

Pfizer recently announced new follow-up data from a worldwide expanded access program supporting the efficacy and safety of single-agent, oral sunitinib malate (Sutent) in the treatment of imatinib (Gleevec)-resistant or intolerant gastrointestinal stromal tumor (GIST). These data were presented at the annual ASCO meeting in Chicago (abstract 10548).

Caris Diagnostics (Caris Dx), a provider of diagnostic, translational development and pharmaceutical services encompassing anatomic pathology and molecular testing, announced that it is now offering KRAS mutation analysis, designed to provide information on which colon cancer patients are most likely to respond to cetuximab (Erbitux), comarketed by ImClone and Bristol-Myers Squibb, or panitumumab (Vectibix) developed by Amgen.

CHICAGO-Sorafenib (Nexavar) is safe and prolongs overall survival and time to progression in Asian patients with advanced hepatocellular carcinoma (HCC), finds the randomized phase III Asia-Pacific liver cancer study. Moreover, efficacy was similar to that in the Western population even though the Asian patients had more adverse prognostic factors.

In this issue of ONCOLOGY, Drs. Patel, Puthillath, Yang, and Fakih discuss the evolution of adjuvant therapy for locally advanced rectal cancer from postoperative to preoperative radiation and provide a fairly comprehensive review of the data on adjuvant/neoadjuvant chemoradiation for rectal cancer. The authors then attempt to critically evaluate the use of combination chemotherapy regimens in the neoadjuvant setting, asking the question, “Is more better?”

Neoadjuvant chemoradiation has become the favored adjuvant treatment for stages II and III rectal cancer. Compared to postoperative chemoradiation, this modality of treatment has been shown to be superior in terms of toxicity, local relapse, and sphincter-saving.[1] This article will focus on the evolution of neoadjuvant chemotherapy over the past 2 decades, current acceptable neoadjuvant standards, and current investigational regimens.

A large, multicenter study has shown that the chemotherapy drug gemcitabine (Gemzar) more than doubles overall survival in patients who have undergone surgery for pancreatic cancer. The CONKO-001 trial is the first large-scaled phase III study to show a benefit for any chemotherapy agent given to early-stage pancreatic cancer patients after surgery to remove their tumors. The trial data were presented by Hanno Riess, md, phd, a professor at Charité University Medical School in Berlin and the leader of the CONKO study group (abstract LBA4504).

A new analysis of a randomized, controlled clinical trial investigating cetuximab (Erbitux) in the treatment of first-line metastatic colorectal cancer (mCRC) highlights the increased efficacy of cetuximab in patients who have tumors with nonmutated (ie, wild-type) KRAS. These results were presented by lead investigator Eric Van Cutsem, md, phd, professor of medicine and digestive oncology from the University Hospital Gasthuisberg in Leuven, Belgium, at the plenary session of the 44th Annual Meeting of the American Society for Clinical Oncology (ASCO), held May 30 through June 3 in Chicago (abstract 2).

SAN DIEGO­-Bevacizumab (Avastin) added to chemoradiation as neoadjuvant therapy for locally advanced rectal tumors led to substantial downstaging and 100% local control at 4 years in a small phase II study reported at the 2008 American Association of Cancer Research annual meeting (abstract LB-304). The study enrolled 32 patients with T3/T4 nonmetastatic rectal cancer from Massachusetts General Hospital and Duke University Medical Center between 2001 and 2007.

ORLANDO-Patients aged 75 and older with metastatic colorectal cancer can be treated with standard combination chemotherapy regimens, despite increased toxicity, according to results of the FFCD 2001-02 trial. French investigators reported planned interim data at the 2008 Gastrointestinal Cancers Symposium (abstract 281).

The National Coalition for Quality Colorectal Cancer Screening and Care, a 501(c)(6) not-for-profit association, recently announced the formation of a broad-based coalition dedicated to reducing the incidence of colorectal cancer through educational programs aimed at promoting colonoscopy screening and care options for patients in a safe and comfortable setting.

Pohl and colleagues have provided a concise overview of current treatment options for metastatic colorectal cancer (mCRC). However, the authors do not provide personal insights as to what direction this burgeoning field will take next.

Dr. Pohl and colleagues have provided a comprehensive and well written overview of the current landscape of targeted agents and chemotherapy in advanced colorectal cancer.

Colorectal cancer is one of the leading causes of cancer-related death worldwide, with almost 20% of all patients presenting with metastatic disease at the time of their diagnosis. The treatment regimens and options of metastatic colorectal cancer have significantly changed in the last 10 years, leading to an improvement of response rates to about 50%, progression-free survival of about 10 months, and overall survival reaching over 2 years.

When GIST patients develop resistance to imatinib (Gleevec), second-line sunitinib (Sutent) has been shown to achieve a response rate of 7% and a median progression-free survival of 6.2 months. When patients progress on sunitinib, however, therapeutic options have been limited.

A phase II study found improvements in recurrence-free and overall survival with adjuvant imatinib (Gleevec) in high-risk GIST patients, compared with historical controls, Ronald P. DeMatteo, MD, reported at the 2008 Gastrointestinal Cancers Symposium (abstract 8).

A serum marker, colon-cancer-specific antigen-2 (CCSA-2), detects nearly 97% of colorectal cancers and can differentiate between advanced adenomatous polyps and less ominous ones, according to investigators from Johns Hopkins and the University of Pittsburgh who have collaborated on research in this area.

Adjuvant therapy is defined as any treatment administered after surgical resection of a primary tumor with the intent of improving the patient’s outcome by eliminating any occult, viable tumor cells that may have remained after surgery.

To treat, or not to treat-the decision to use adjuvant chemotherapy plagues medical oncologists and patients harnessed with the diagnosis of stage II colon cancer. A look to the literature does not simplify the decision, as significant controversy exists regarding the magnitude of benefit associated with 6 months of adjuvant chemotherapy. Dr. Kopetz and colleagues provide a well-organized review of the current literature examining the benefit of adjuvant chemotherapy in stage II disease, and discuss potential prognostic markers that may help determine who would most likely benefit from treatment.

New data revealing decreasing trends in cancer deaths in the United States overall, and in colorectal cancer deaths in particular, highlight the remarkable benefits of colorectal cancer screening tests, but the lifesaving potential of these tests is unrealized for many Americans, according to experts from the American College of Gastroenterology (ACG).

new Mayo Clinic study found that 40% of pancreatic cancer patients are diagnosed with diabetes prior to their pancreatic cancer diagnosis

Gastrointestinal stromal tumors have until recently had a uniformly poor prognosis with lack of effective drug therapies. These tumors usually have activating mutations in either KIT or PDGFR-α tyrosine kinase receptors. Over the past decade, imatinib (Gleevec), a selective tyrosine kinase inhibitor has become the standard of care for the first-line treatment of patients with unresectable and metastatic disease. For patients with imatinib-resistant disease or intolerant to the side effects of imatinib, sunitinib (Sutent), a multitargeted tyrosine kinase inhibitor was recently approved. For earlier-stage disease, status post–complete surgical excision, preliminary data seem encouraging for the role of adjuvant imatinib in prolonging patients' disease-free interval. The impact of neoadjuvant drug therapy needs to be further classified and explored. With additional evaluation of other tyrosine kinase inhibitors and novel therapies against other molecular markers, the treatment paradigm for this malignancy should continue to evolve.