Pancreatic cancer therapies emerge

Key Points

Patrick Swayze's recent pancreatic cancer diagnosis has raised public awareness about this lethal carcinoma. Pancreatic cancer poses a significant therapeutic dilemma for clinicians. A majority of the patients present with locally advanced or metastatic disease at the time of diagnosis, with the tumor often being chemoresistant. "Researchers are looking for drugs that will improve overall survival better than current treatments, which have shown to be only somewhat beneficial," Mohamed Muhsin, MSc, MBA, senior oncology analyst at market research firm Decision Resources in Waltham, Mass., said.

The standard chemotherapy for pancreatic cancer, gemcitabine (Gemzar, Eli Lilly), offers modest improvement of tumor-related symptoms and marginal advantage of survival. However, other treatments are emerging. They include:

Immunotherapy

Pharmexa's investigational vaccine, GV1001, recently suffered a setback in a phase III study, which compared it with gemcitabine in sequential combination to gemcitabine monotherapy in advanced pancreatic cancer. Preliminary data showed no survival benefit in the GV1001 group compared with gemcitabine. Despite these disappointing results, another study comparing gemcitabine, capecitabine, plus GV1001 therapy with gemcitabine and capecitabine alone is underway.

Another immunotherapy product in the pipeline is GVAX (Cell Genesys). Preliminary study results showed a median survival of 26.8 months in patients who received the immunotherapy after surgical resection of their tumor and standard chemotherapy. This compares favorably with published data from other studies in pancreatic cancer patients that have shown a median survival of 17 to 22 months.

Biological agents in pancreatic cancer

"Novel targeted agents that antagonize the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) pathways have recently been the focus of research in pancreatic cancer," Muhsin said.

Blockade of the EGFR pathway with the tyrosine kinase inhibitor erlotinib (Tarceva, Genetech/OSI), used in combination with gemcitabine, has shown to improve survival in several studies.

Axtinib (Pfizer), an investigational selective inhibitor of VEGFR, combined with gemcitabine, showed a trend toward prolonged overall survival in advanced pancreatic cancer patients in a phase II study. Based on these study results, a double-blind phase III trial is planned to determine further efficacy of axtinib.

The anti-VEGF antibody, bevacizumab (Avastin, Genentech/Roche), has been evaluated in several studies with patients with advanced pancreatic cancer. In a phase II study presented at the Gastrointestinal Cancers Symposium 2008 meeting, patients who received gemcitabine, capecitabine, and bevacizumab had a median progression-free survival and overall survival of 5.8 and 9.8 months, respectively.

More novel agents

Other investigational agents for pancreatic cancer include Genexol-PM (GPM), which is a micellar formulation of the chemotherapy agent paclitaxel. Preclinical and phase I studies have shown that GPM has lower toxicity and better efficacy than paclitaxel. Results of a phase II study demonstrated that GPM given every three weeks was well tolerated and resulted in progression-free survival similar to that seen historically with gemcitabine.

At the American Society of Clinical Oncology (ASCO) 2008 meeting, researchers announced that a study evaluating combined use of hyperthermia and chemotherapy in pancreatic cancer patients is underway. Prelimimary data indicated that one-year survival in patients treated with gemcitabine plus hyperthermia was 49 percent versus 30 percent for the gemcitabine monotherapy group.

PHY906, a traditional Chinese medicine botanical, is being evaluated in a study assessing the efficacy and quality of life in gemcitabine-refractory pancreatic cancer patients.

According to Decision Resources, several emerging therapies that had shown early promise have since failed to show improved survival over standard therapy in recent studies. Products that have fallen at this hurdle include oxaliplatin (Eloxatin, Aventis), pemetrexed (Alimta, Eli Lilly), irinotecan (Camptosar, Pfizer), and PANVAC-VF vaccine (Therion Biologics).

Catch it early

"Due to its late onset of symptoms, pancreatic cancer often goes undetected until it's too late," Joseph Geenen, MD, director of pancreatic and biliary services at Aurora St. Luke's Medical Center in Milwaukee, Wis., said. Because of the genetic nature of pancreatic cancer, Geenen recommends that those with a familial history or conditions, such as hereditary tumor syndrome, be screened.

To help kick off the Familial Pancreatic Cancer Initiative, actress and Milwaukee native Charlotte Rae was screened by Geenen. "It is my hope that with early detection, we can elevate the survival rate and give our patients a fighting chance to be a pancreatic cancer survivor," Geenen said.

MONICA SHAH is a writer and hospital pharmacist based in New Jersey.