Pancreatic Cancer: Still Grim Reaper

Pancreatic cancer is the 10th most common oncological diagnosis, but the third leading cause of cancer mortality in the United States today. Each year approximately 30,000 people in this country are diagnosed as having this lethal neoplasm. And what's even more disturbing is that a majority of these patients will have expired by the end of the first year. "Despite tremendous endeavors in the past few decades, conventional therapeutic modalities have had minimal effect on the course of this aggressive disease," said Maya Shah, M.D., an oncologist at Newark Beth Israel Medical Center in New Jersey.

Chemo for pancreatic cancer For most pancreatic cancer patients, available treatment options are limited. More than 30 chemotherapeutic agents have been investigated over the past 20 years with frustrating results; response rates below 10% and a median survival of less than six months have been reported. For metastatic disease, chemotherapy is never curative, and its potential palliative benefit must be carefully weighed against toxic side effects.

"In an effort to improve the response rates, combination regimens with gemcitabine and other chemotherapy agents have also been investigated," stated Shah. Results of three different randomized trials of gemcitabine-based combinations were reported at the 2003 meeting of the American Society of Clinical Oncology (ASCO). First, while the combination of gemcitabine and irinotecan (Camptosar, Pfizer) demonstrated a response rate superior to gemcitabine alone, this did not translate into improvement in time-to-disease progression or overall survival.

Another study, comparing gemcitabine plus oxaliplatin (Eloxatin, Sanofi-Aventis) with gemcitabine alone, showed that combination therapy produced a better clinical response rate and a benefit in time-to-disease progression. One promising regimen, combining gemcitabine and cisplatin, has demonstrated an advantage over gemcitabine alone for both progression-free and overall survival in patients with metastatic or locally advanced disease.

Demonstrating synergistic cytotoxicity against pancreatic cancer cells is the GTX regimen, which comprises the three chemotherapy drugs, gemcitabine, docetaxel (Taxotere, Aventis), and capecitabine (Xeloda, Roche). In a study presented at ASCO's 2004 meeting, the median survival for all 35 patients treated with the GTX regimen was at least 8.6 months and 10.5 months for patients who completed three cycles. "The GTX regimen demonstrates an excellent response rate and superior survival of a group of patients with an extremely poor prognosis," concluded Robert L. Fine, M.D., the lead study investigator, Columbia University Medical Center.

Other agents in the pipeline Threshold Pharmaceuticals' lead product candidate, glufosfamide, is in clinical development for the treatment of pancreatic cancer. Glufosfamide combines the active part of an approved alkylator, ifosfamide, with a glucose molecule.