Pancreatic Cancer

The case of recurrent pancreatic cancer presented in this issue of ONCOLOGY by Dr. Dasari and colleagues illustrates the significant challenges faced by both medical and surgical oncologists in the management of pancreatic adenocarcinoma. This case describes an all-too-common clinical scenario: A thorough preoperative assessment indicating resectable disease, but with the initial medical oncology assessment revealing overt metastatic disease. The development of distant metastases in the short interval between pre-operative and post-operative staging reflects the aggressive underlying biology associated with a subset of patients with this malignancy. New insight into the genetic evolution of pancreas adenocarcinoma from Yachida and colleagues suggests that the latent period between initial development of pancreas adenocarcinoma and development of metastases is measured in years, however detection of the diagnosis at an early stage remains an ongoing challenge for clinicians.[1]

In this issue of ONCOLOGY, the case and discussion provided by Dasari and colleagues highlight a significant problem for many patients with potentially resectable pancreatic cancer (PC)-the rapid emergence of preexisting metastatic disease. The authors describe the case of a 57-year-old woman with a resectable tumor after staging evaluation and management which included an endoscopic ultrasound (EUS), CT imaging, and endoscopic retrograde cholangiopancreatography (ERCP) with insertion of an endobiliary stent. Although the results from EUS are not detailed in the report, there were apparently no preoperative features to suggest more advanced disease, and she underwent surgery. Four weeks later, she presented with advanced disease manifested by an elevated CA 19-9, bilobar liver metastases, and possible local recurrence. This case illustrates some important considerations in the management of PC as we discuss here.

The University of Colorado Denver School of Medicine faculty hold weekly second opinion conferences focusing on cancer cases that represent most major cancer sites. Patients seen for second opinions are evaluated by an oncologic specialist. Their history, pathology, and radiographs are reviewed during the multidisciplinary conference, and then specific recommendations are made. These cases are usually challenging, and these conferences provide an outstanding educational opportunity for staff, fellows, and residents in training.The second opinion conferences include actual cases from genitourinary, lung, melanoma, breast, neurosurgery, gastrointestinal, and medical oncology. On an occasional basis, ONCOLOGY will publish the more interesting case discussions and the resultant recommendations. We would appreciate your feedback; please contact us at second.opinion@uchsc.edu.

The search for a magic bullet against cancer historically has glowed bright then dimmed, depending on the stage of discovery. Developments surrounding monoclonal antibodies and angiogenesis inhibitors have followed this cycle, as exuberance for their potential has bowed to the nuances that underlie the complex mechanisms on which they depend.

In a large study of resected pancreatic cancer, overall survival did not differ whether patients received gemcitabine or 5-FU/folinic acid.

A novel IGF-receptor inhibitor stabilized disease in a majority of pancreatic cancer patients, according to a report at the 2010 GI Cancers Symposium.

Screening is the key to protecting those at risk for pancreatic cancer, according to presenters at the 2010 Gastrointestinal Cancers Symposium.

Although still relatively uncommon in Western countries, esophageal cancer is fatal in the vast majority of cases. In the United States, an estimated 16,470 new cases will be diagnosed in the year 2009, and 14,530 deaths will result from the disease. This high percentage of deaths rivals that of pancreatic cancer and is more than four times that of rectal cancer.

Pancreatic cancer is the fifth leading cause of cancer death in the United States. In the year 2009, an estimated 42,470 new cases are expected to be diagnosed, and 35,240 deaths are expected to occur.

GenVec, Inc, announced that the US Food and Drug Administration (FDA) has granted orphan drug designation to TNFerade for the treatment of pancreatic cancer.

In patients with resected pancreatic cancer, adjuvant cisplatin, 5-FU, and interferon chemoradiation produces a median survival of 27 months, according to initial results of the ACOSOG Z05031 trial. However, nearly all patients experience grade 3 or 4 toxicities.

Metformin reduces an individual’s risk of developing pancreatic cancer by 62%, according to research from Houston’s M.D. Anderson Cancer Center. Metformin is the most commonly prescribed drug for patients with type 2 diabetes, who are often obese and/or have insulin resistance.

Common variants of the gene that determines human blood type are associated with an increased risk of pancreatic cancer, according to a study by scientists at the National Cancer Institute (NCI) and colleagues from many universities and research institutions. The study, published online August 2, 2009, in Nature Genetics, is consistent with an observation first made more than 50 years ago.

Young adults who are overweight or obese have an increased risk of pancreatic cancer, according to a study out of M.D. Anderson Cancer Center. In addition, the Houston-based researchers found that obesity at an older age is associated with a lower overall survival rate for patients with pancreatic cancer.

Pfizer announced results from a randomized phase III trial of sunitinib malate (Sutent) in patients with advanced pancreatic islet cell (neuroendocrine) tumors

A phase III clinical trial of sunitinib (Sutent) has been stopped early after the drug showed significant benefit in patients with advanced pancreatic neuroendocrine tumors. An independent data monitoring committee recommended halting the trial after concluding that sunitinib demonstrated greater progression-free survival compared with placebo plus best supportive care in these patients.

In this case report, we discuss the presentation, workup, and therapeutic management of a 40-year-old man who presented with borderline resectable, periampullary pancreatic cancer and underwent a margin-negative resection following neoadjuvant chemoradiotherapy.

The authors describe the case of a 40-year-old man with an adenocarcinoma of the pancreatic head with involvement of the superior mesenteric vein–portal vein (SMV-PV) confluence resulting in limited occlusion.

STOCKHOLM-A novel anti-neovascular therapy substantially extended survival time over standard gemcitabine (Gemzar) therapy in pancreatic cancer patients, according to the results of a phase II study presented at ESMO 2008 (abstract LBA7).

Localized pancreatic cancer, whether resectable or unresectable, is a separate entity from metastatic pancreatic cancer. Multiple studies have demonstrated that even in the setting of unresectable disease, the progression-free and overall survival of patients with localized pancreatic cancer exceeds that associated with metastatic pancreatic 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.

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.

Between YouTube and MySpace, it doesn’t take much to become an Internet sensation. But Randy Pausch, PhD, may have been one of the few Web stars who deserved the attention.

CHICAGO-Compared with observation, adjuvant gemcitabine (Gemzar) reduces the risk of recurrence by 45% and the risk of death by 28% in patients with resected pancreatic cancer, according to final results of the CONKO-001 trial.

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.

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).

Last month, ONI reported evidence from two retrospective studies and one phase II trial for the use of adjuvant chemoradiation in resected pancreatic cancer patients (Feb. 2008, pages 1 and 31). Now, RTOG investigators report a strong trend toward improved survival in patients with resected cancer of the pancreatic head with gemcitabine (Gemzar) plus fluorouracil (5-FU)-based chemoradiation, compared with standard 5-FU chemoradiation (JAMA 299:1019-1026, 2008).

Patients who undergo complete resection of invasive adenocarcinoma of the pancreas are roughly two-thirds more likely to be alive at 5 years if they receive adjuvant chemotherapy and radiation therapy, compared with no adjuvant therapy, according to the 30-year Mayo Clinic experience.

Overall survival after pancreatic resection can be markedly improved with adjuvant chemoradiation therapy, according to investigative groups who presented encouraging data on two different regimens at the 2008 Gastrointestinal Cancers Symposium.