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Pancreatic Cancer

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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 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.

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.

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).

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.

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).