Between May 2003 and January 2005, 533 patients with previously untreated or cytological proven locally advanced/metastatic carcinoma of the pancreas were randomised to receive either gemcitabine treatment alone, or gemcitabine and capecitabine treatment. Treatment continued until the disease progressed or the side effects/toxicity effects became intolerable. The primary outcome was survival.
At the time of the interim analysis in May 2005, 70% of deaths had occurred. The median survival for gemcitabine alone and gemcitabine and capecitabine was 6 months and 7.4 months respectively but 1-year survival rates were 19% and 26% respectively. Toxicity effects recorded in both treatment groups included anaemia, neutropenia, thrombocytopenia, fever, diarrhoea and vomiting.
The investigators concluded there was a significant improvement in overall survival by the addition of capecitabine to gemcitabine over gemcitabine alone in advanced pancreatic cancer with acceptable levels of toxicity.
Dr Ian Chau from the Royal Marsden Hospital, UK, commented, ¡°The combination of gemcitabine and capecitabine confers a survival advantage over standard gemcitabine monotherapy and may be considered as a new standard of care in advanced pancreatic cancer. Patients will enjoy an improvement in survival with an acceptable level of side effects. This combination could form a new treatment platform to which novel molecular targeted therapy can be added.¡±
About pancreatic cancer
Pancreatic cancer is a very aggressive cancer with an extremely low survival rate. It is very difficult to detect and can be without symptoms until it has reached an advanced stage; most patients die within 6 months of diagnosis.1
Pancreatic cancer is the tenth most frequently occurring cancer in Europe.2 It is associated with smoking tobacco and does have a strong hereditary component.3 It does not usually appear before the age of forty. 3There are many types of cancer but the vast majority are exocrine type (affect the release of pancreatic enzymes for the digestive system), others affect the endocrine system, the release of hormones such as insulin.
Pancreatic cancer is difficult to treat and is often resistant to chemotherapy and radiotherapy. Normally surgical removal of the cancer is the best chance for patients and the most widely used surgical technique is called a pancreaticoduodenectomy (PD) or Whipple procedure. However, newer drugs in clinical trials and chemotherapy options such as the administration of gemcitabine and capectiabine are offering patients some treatment options.
1 www.cancer-info.com
2 www.startoncology.net
3 www.pancreaticcancer.org
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Abstract: Presidential symposium
Phase III randomised comparison of gemcitabine (GEM) versus gemcitabine plus capecitabine (GEM-CAP) in patients with advanced pancreatic cancer
D. Cunningham1, I. Chau1, D. Stocken2, C. Davies3, J. Dunn2, J. Valle4, D. Smith5, W. Steward6, P. Harper7, J. Neoptolemos8
1Royal Marsden Hospital, Medicine, Sutton, United Kingdom
2University of Birmingham, CRUK Trials Unit, Birmingham, United Kingdom
3Royal Liverpool University Hospital, CRUK Trials Office, Liverpool, United Kingdom
4Christie Hospital, Oncology, Manchester, United Kingdom
5Clatterbridge Centre for Oncology, Oncology, Liverpool, United Kingdom
6Leicester Royal Infirmary, Oncology, Leicester, United Kingdom
7Guy's Hospital, Oncology, London, United Kingdom
8Royal Liverpool University Hospital, Surgery, Liverpool, United Kingdom
Background:
Both gemcitabine and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This study was designed to compare the survival of gemcitabine (GEM) with gemcitabine plus capecitabine (GEM-CAP).
Methods:
Patients with previously untreated histological or cytological proven locally advanced/metastatic carcinoma of the pancreas and performance status ¡Ü2 were recruited. Patients were randomised to GEM (1000mg/m2 weekly X7 q8 weeks, then 1 week rest, thereafter weekly X3 q4 weeks) or to GEM-CAP (gemcitabine 1000mg/m2 weekly X3 q4 weeks and capecitabine 1660mg/m2/day for 21 days followed by 7 days' rest). Treatment continued until disease progression or intolerable toxicities. The primary outcome measure was survival.
Results:
Between May 02 and Jan 05, 533 patients were randomised to GEM (n=266) and GEM-CAP (n=267) arms. Baseline characteristics were well balanced (GEM/GEM-CAP) with regards to median age (62/62), stage IVB disease (71%/70%) and WHO performance status (PS) 0-1 (82%/81%). At the time of this interim analysis in May 05, 373 (70%) deaths have occurred. GEM-CAP significantly improved overall survival over GEM alone (Hazard Ratio [HR]: 0.80; 95% CI: 0.65-0.98; p=0.026). The median survival for GEM and GEM-CAP was 6 months and 7.4 months respectively and 1-year survival rates were 19% and 26% respectively. After adjusting for baseline stratification factors (disease extent and PS), the survival advantage for GEM-CAP remains (HR: 0.77; 95% CI: 0.63-0.95; p=0.014). The objective response rates were 7% (0CR, 19PRs) and 14% (3CRs, 35 PRs) in GEM and GEM-CAP respectively (p=0.008). Grades 3/ 4 toxicity episodes in GEM and GEM-CAP arms respectively were anaemia (2%/1%), neutropenia (11%/17%), thrombocytopenia (2%/3%), fever (1%/0%), diarrhoea (1%/1%), stomatitis (0%/0%), hand foot syndrome (0%/2%) and vomiting (2%/1%)
Conclusions:
With 70% death having occurred, these data show a significant improvement in overall survival by the addition of capecitabine to gemcitabine over gemcitabine alone in advanced pancreatic cancer with acceptable levels of toxicity.