Gastrointestinal Cancer

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.

blood-based marker called colon cancer–specific antigen-2 (CCSA-2) may be an accurate indicator of colorectal cancer

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.

Complete evaluation of the lymph node basin after surgical resection for colon cancer is important for the accurate identification of nodal involvement and for the complete resection of disease.

Data published in the New England Journal of Medicine show that oral capecitabine (Xeloda) and oxaliplatin (Eloxatin) in combination with epirubicin (Ellence) is a comparable alternative to infused fluorouracil (5-FU) and cisplatin with epirubicin in patients with previously untreated, advanced esophagogastric cancer.

Sunitinib malate (Sutent, SU011248) is an oral multitargeted tyrosine kinase inhibitor used for treatment of renal cell carcinoma and gastrointestinal stromal tumor. We report a case of a patient who developed Guillain-Barré syndrome after initial treatment with sunitinib, with recurrent symptoms upon reintroducing the drug. This is the first report of such an effect. The literature on chemotherapy-induced Guillain-Barré syndrome is also reviewed. Oncology providers should be aware of this rare but potentially serious possible adverse effect of sunitinib.

Sunitinib malate (Sutent, SU011248) is an oral multitargeted tyrosine kinase inhibitor used for treatment of renal cell carcinoma and gastrointestinal stromal tumor. We report a case of a patient who developed Guillain-Barré syndrome after initial treatment with sunitinib, with recurrent symptoms upon reintroducing the drug. This is the first report of such an effect. The literature on chemotherapy-induced Guillain-Barré syndrome is also reviewed. Oncology providers should be aware of this rare but potentially serious possible adverse effect of sunitinib.

multicenter, open-label, randomized phase III trial recently published in the New England Journal of Medicine (357:2040-2048, 2007) demonstrated that cetuximab (Erbitux) as a single agent significantly improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to approved chemotherapy agents.

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.