Biliary tract cancer (BTC) afflicts 8,000 patients in the US each year. It is separated into intrahepatic (within the liver) and extrahepatic (gallbladder and common duct). For years, there was no treatment beyond 5-fluorouracil (5-FU). Response rates were low, and there were no cures in advanced disease.
Biliary tract cancer (BTC) afflicts 8,000 patients in the US each year.
Biliary Cancer: Miraculous Response
In the 1990s, our laboratory discovered activity for cisplatin plus gemcitabine in upper gastrointestinal tract cancers. One response was so remarkable that it resulted in an article in the Scientific American (In Focus, Pretesting Tumors, February 1999, E. Strauss, PhD).
This article described a miraculous response in a patient with metastatic upper gastrointestinal cancer using cisplatin plus gemcitabine selected for him in the laboratory, which lasted years.
Fast forward 10 years: the American Society of Clinical Oncology “discovers” cisplatin and gemcitabine for biliary cancer, as reported to great fanfare at the ASCO meeting, and Cisplatin plus Gemcitabine becomes the “new” standard-of-care for the disease.
Yet, 16 years later, there has been no substantive advance. Since our discovery of this doublet, there’s been no evidence that the addition of immune therapy, a third drug, or other combinations have meaningfully improved outcomes for patients with this lethal disease.
A recent article in the Journal of Clinical Oncology (Wang X, Oncology Grand Rounds, January 7th, 2025) reviews the data and comes to a disturbing conclusion: “After screening 8,797 studies, 17 randomized controlled trials were selected encompassing a total of 4,584 patients… Collectively, this data indicates that recent efforts to intensify therapy whether through triplet chemotherapy regimens or the addition of checkpoint inhibitors have resulted in only modest improvements in OS (overall survival).”
For anyone afflicted with this lethal disease, it should be obvious that the medical oncology community has failed them. No matter how sophisticated the analytical tools, the oncology community cannot define the right treatment. Clinical trials are not answering these critical questions fast enough to save lives.
So, let’s examine what these investigators have discovered.
1) The most active backbone for treatment is the one that our laboratory platform found 26 years ago.
2) The highly synergistic interaction between cisplatin and gemcitabine, the subject of our textbook (Deoxynucleoside Analogs in Cancer Therapy, Humana Press 2006) used patient tumor testing to discover this combination’s profound clinical activity.
3) The lesson these doctors are absolutely unwilling to learn is that to explore human cancer biology, you must study human cancer biology.
4) Biological phenomena are so complex that no genomic, transcriptomic, or proteomic profile can possibly answer these life and death questions.
Indeed, for patients with biliary tract cancer, selecting between: gemcitabine plus cisplatin, gemcitabine plus cisplatin and nab-paclitaxel, cisplatin plus gemcitabine and 5-FU, FOLFOX, FOLFIRINOX, pemigatinib or ivosidenib, or other combinations turns out to be quite easy. We do it every day!
Biliary tract cancer patients - or for that matter, all cancer patients - must throw off the yoke of contemporary clinical trials and insist that their surgeons submit tissue for drug response analysis.
The only way forward for cancer patients is to get the right treatment the first time, every time.
This can only be accomplished by studying each patient’s tissue. No other approach is working.