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Pancreas cancer main Resources Pancreatic cancer news  

Advances in pancreatic cancer treatment


Introduction
Gemcitabine is the standard first line therapy for pancreatic cancer. Several gemcitabine based chemotherapy combinations were studied for the treatment of pancreatic cancer, but none of these combination chemotherapies showed any significant benefit over single agent gemcitabine in the treatment of pancreatic cancer. Targeted therapies have recently entered in to the treatment of pancreatic cancer.

Erlotinib (Tarceva) and pancreatic cancer
Findings from a study combination of small molecule EGFR Tyrosine kinase inhibitor erlotinib with gemcitabine in pancreatic cancer was presented at 2005 ASCO gastro-intestinal Cancer symposium that was held in Hollywood, FL. The study was presented by researchers form the National Cancer Institute of Canada. This is a phase III trial comparing the combination of erlotinib plus gemcitabine to gemcitabine plus placebo in advanced pancreatic cancer. Overall survival was the endpoint of the study.

Patients who participated in the study had advanced pancreatic cancer and had not received any prior chemotherapy except that was given with radiation therapy. EGFR over-expression was not required as a condition for enrollment in to the study.

Gemcitabine dose was 1000mg/m2/week IV for 7 of first 8 weeks as first cycle. From the second cycle onwards gemcitabine was given weekly for 3 weeks in four-week cycles at the same dose. Patients were randomized to receive placebo, 100mg/day or erlotinib or 150mg/day of erlotinib.

The following are the highlights from the study:

  • A total of 569 patients were treated with gemcitabine plus erlotinib (including both dose levels)
  • Total of 284 patients were treated with gemcitabine plus placebo
  • Gemcitabine plus erlotinib arm Vs gemcitabine plus placebo arm showed the following results respectively
  • No significant increase in objective response rate (8% Vs 9%)
  • Increased overall survival (6.37 months Vs 5.9 months) p=.025
  • Improved one-year survival (24% Vs 17%)
  • Median time to progression (3.75 months Vs 3.55 months) p=.003
  • Skin rash increased (6% Vs 1%)
  • Diarrhea increase (6% Vs 2%)
Overall grade 3 to 4 adverse events were not significantly increased with the addition of erlotinib to gemcitabine.

Erbitux (cetuximab) and pancreatic cancer
Cetuximab is a chimeric monoclonal antibody that binds to EGFR and has been approved for treatment of relapsed refractory metastatic colon cancer. In a recent phase II clinical trial patients who had locally advanced or metastatic pancreatic cancer has been treated with a combination of cetuximab and gemcitabine. Patients who participated in the study did not get any prior chemotherapies, and had immuno-histo-chemical evidence for EGFR expression. Patients received an initial dose of 400mg/m2 followed by a weekly maintenance dose of 250mg/m2 of cetuximab. Patients also received gemcitabine. Gemcitabine was given at a dose of 1000mg/m2 IV initially weekly for 7 weeks, followed by one-week rest. After the first cycle gemcitabine was given once week for three weeks of a four-week cycle.

The following are the highlights of the study:
  • Total patients 41
  • Partial response 5 (12%)
  • Stable disease 26 (63%)
  • Overall survival 7.1 months
  • Median time to progression 3.8 months
  • One-year progression free survival 12%
  • One-year overall survival 32%
  • Most frequent side effects: neutropenia, asthenia, abdominal pain, and thrombocytopenia
Bevacizumab (Avastin) and pancreatic cancer
Bevacizumab is an anti-angiogenic drug directed against VEGF receptor. A phase II study using a combination of bevacizumab and gemcitabine in advanced pancreatic cancer has been reported in the 2004 meeting of the American Society of Clinical Oncology (ASCO).

The following are the highlights from the study:
  • Total of 52 evaluable patients
  • Partial response 10 (19%)
  • Stable disease 25 (48%)
  • Median survival 8.7 months
  • One-year survival 29%
A randomized phase III clinical trial CALGB 80303 is ongoing to validate the results of this study.

Tipifarnib in pancreatic cancer
Tipifarnib is a drug that inhibits farnesylation of the Ras protein. A phase III compared combination of Tipifarnib plus gemcitabine against gemcitabine plus placebo in previously untreated patients with advanced pancreatic cancer.

The following are the highlights from the study:
  • Overall survival not improved (193 days Vs 182 days)
  • Time to progression not improved (202 days Vs 136 days)
  • Grade 3 to 4 neutropenia (40% Vs 30%)
  • Febrile neutropneia (14% Vs 6%)


Cancer terms:
Relapse: Relapse is used interchangeably with recurrence. See Recurrence aboveSee cancer terms for more cancer related terms.

Medicineworld.org: Advances in pancreatic cancer treatment

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