Here is what I get from the presentation title " Treatment of biliary tract and Gallbladder Cancer" by Dr. Jordan Berlin MD.
There are about 7,500-8,000 new cases per year. ( I believed he means in the States,but I am not 100% sure.)
Currently Gemzar+the platins(cisplatin,Oxaliplatin and Carpoplatin) provide the highest response rate(RR=22-48%);time to disease progress(TTP 7-13months) and overall survival(OS=7-13months).
A 5FU pooled analysis shown RR=22.6%;TTP=4.1 months & OS=8.2months.
Other chemo agents like irinotecan and the Taxanes (ie: docetaxel, Paclitaxel) ;the RR=20%;TTP=6months and OS=8months for a study done for docetaxel involved 25 patients; and there were no RR in a study done for Paclitaxel which involved only 15 patients.
He indicated that there may be biological and pathological differences in biliary cancers; and we are near the limit of where the cytoxic agents can do(ie: traditional chemo agents. );therefore we have look beyond the cytoxics and into the targeted therapies.
For target therapies,we have to look at the pathways first in order to determine where to start ;biliary cancer is a rare cancer and therefore it may be impossible to test every pathways to find new drugs;so we have to choose the pathways wisely. Currently there are overexpression in biliary cancer in MAP kinase pathways like EGFR;C-met(ICC=20% overpressed and ECC=16%);Kras mutation is about 50% in ECC and less in other sites.
Erlotinib(single agent study,42patients,RR=7%,17% of patients is PFS=6months ,benefit is modest at best) , cetuximab and panitumumab are EGFR inhibitor examples under study too.
MEK pathway is another pathway. In a study involved 28 patients ,using Selumetinib as a SINGLE agent in the 28 pts study;RR=12% PFS=3.7month and OS=9.8months; another MEK inhibitor under study is MEK 162 in phase I.
Other pathways are BRAF,PI3kinase;TGF beta etc. currently studies are in development to explore these pathways in order to search for new drugs to combat the biliary cancer;but due to the fact that there are biological and pathological differences in biliary cancer(ie:ICC vs ECC);we should approach the problems by targeting on different tumor sites, the disease as well as targeting the mutations.
Cell cycling is another pathway since our body cells are cycling all the time,and that is why it is dangerous since the cells keep growing.Examples of the cell cycling factors are p27,BcI2.p53 etc. the abnormality are different by site(ie: ICC,distal,Hilar). the agents that potentially useful are WEE1,CHK1etc.
The site of recurrence of biliary cancer in ICC patients : intrahepatic =54%; extrahepatic=24% and Intra+Extra =22%. Overall the recurrence rate is >75%.
Conclusions: The future belong to targeted therapy;currently chemotherapy is still the standard of biliary treatment . The Level 1 evidence standard treatment is GEM/CIS. In treating biliary cancer,we have to target the disease as well as the mutations in research and treatment of biliary disease.
Adjuvant therapies provide NO definitive evidence that will benefit the patients.It depends on the site of the Primary(ie:ICC,Hilar or distal).
It is possible that adjuvant treatment like radiation will have differential effect depending on site of the primary
Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.