Sorafenib:A New Treatment For Primary Liver Cancer

A presentation this afternoon at ASCO’s annual meeting this afternoon in Chicago  is going to discuss the effectiveness of an oral targeted therapeutic drug called sorafenib (Nexavar) in the treatment of primary liver cancer.


(We need to distinguish primary liver cancer—which originates in the liver and is known by its medical name hepatocellular carcinoma—from cancers that spread to the liver from other organs, such as breast, lung and colon cancer.)


The report is important because up until now there have been no really effective chemotherapeutic agents to treat this form of cancer.  In addition, this treatment is given by mouth, and the side effects were relatively modest.  In fact, the same level of side effects occurred both in the patients who took the drug, and those who took a placebo.


The researchers are going to report that the patients who took sorafenib lived a median of 10.7 months, while those who took the placebo (or dummy pill) lived a median of 7.9 months.  (Median is a statistical measure that means half of the patients lived longer than a particular time, while half the patients died before that time).


Looked at another way, the patients who took sorafenib took about 5.5 months until their disease showed that it was progressing.  Those on the placebo had evidence of disease progression at 2.8 months.


In essence, the drug increased the survival of the typical patients with primary liver cancer about 2.8 months.


That doesn’t sound like much, but it is likely a real finding.  In fact, if you understand what median means, some of the patients in this trial probably lived longer than the 10.7 months. 


And, if you have read my blog previously, you have seen me write that the history of improvements in the treatment of cancer happen much more often in small increments and not in big “one-time” gains.


This report is also important for some of the other considerations beyond extending life for 2.8 months.


First, if you read the information above correctly, you will note that in this particular international clinical trial, the drug was compared to a placebo.   A placebo, more commonly called a “dummy pill” or a “sugar pill” is essentially a pill with no active ingredient and not intended to have a beneficial therapeutic effect.


I am not aware of many clinical trials in cancer that compare a new drug for treating a cancer against a placebo.  You just don’t see that happen very often in cancer research these days.  


So why a placebo?  After all, although liver cancer is less common in the United States, there MUST be a standard treatment to offer.


I checked my trusted resource on the topic—the National Comprehensive Cancer Network website—to see what they recommended for standard chemotherapy treatment.


In fact, for metastatic or recurrent or unresectable primary liver cancer, there IS no standard chemotherapy listed.  Nothing at all.


They do recommend clinical trials or best supportive care (that is medical language for making someone comfortable but not actively treating them with chemotherapy or other modalities) if someone can’t be treated with standard methods or has recurrent disease.


So the bottom line is that we don’t have much to offer patients in these circumstances.


That is not to say we don’t have treatments to offer patients with liver cancer.  But those treatments are more surgically oriented such as surgically removing the cancer when possible, or even transplanting the liver in a patient with liver cancer who meets certain criteria.


There are other techniques as well where doctors can “ablate” the cancer by using freezing techniques, microwave or what is called radiofrequency ablation, for example.


Liver cancer is becoming more common in the United States with 19,160 new cases expected to be diagnosed in the United States according to the American Cancer Society’s Cancer Facts and Figures 2007.  The large majority of patients with this cancer are men, and in 2007 we estimate that 16,780 people in this country will die from this disease.


This is, according to one of my colleagues, one of the cancers that is increasing most rapidly in the United States in men.


This is a cancer that is known to primarily be caused by infection with Hepatitis B and Hepatitis C.


Fortunately, in this country, we have a decreasing incidence of hepatitis, in no small part because we are able to offer immunization against hepatitis B to our children.  We have also significantly improved our ability to test blood transfusions for these viruses, which used to be a significant means of transmission on this virus.


But we also must keep in mind that primary liver cancer is a significant world-wide health risk, in no small part due to the fact that immunization is not widely practiced, and personal and medical hygiene habits are much worse in many developing countries than they are here in the United States.


In fact, in 2005, my colleagues at the American Cancer Society who write Cancer Facts and Figures provided an entire special section of this valued reference book devoted to the topic of infectious causes of cancer in the world.  Liver cancer was the lead topic of discussion.


That monograph contained some interesting statistics:


In 2005, it was estimated there would be 667,000 cases of primary liver cancer throughout the world, making liver cancer the 6th most common cancer in the world.  It is the 18th most common cancer in the United States.


83% of the new cases of liver cancer occur in developing countries., but in the United States the incidence of liver cancer has been occurring for the past 20 years.


In the developing countries, 37% of the new cases of liver cancer are attributable to hepatitis B infection, 25% to hepatitis C, and 10% to liver fluke infections.


Sharing of needles, poor personal hygiene and direct person-to-person transmission account for many of the hepatitis B and hepatitis C infections.


In the United States, we are able to offer treatment for chronic hepatitis infections, but we don’t know how much of an impact this has on the transformation to liver cancer.  In the developing world, these types of treatments are far less available.


So what does all of this mean?


We are fortunate to have a new drug that is clearly effective—albeit modestly—in the treatment of this previously untreatable disease.  That offers some hope, but more importantly signals the opportunities for real advances in the treatment of primary liver cancer.


We also need to understand this is a disease that, although certainly of concern in the United States, is a major health threat throughout the world especially in developing countries.


Liver cancer is a disease that would occur less frequently if we had an effective international immunization strategy and an educational strategy focused on good health and hygiene behaviors and improvements in medical care delivery systems (such as avoiding the reuse of needles in medical settings).


But this is difficult to accomplish, and many barriers are in place which prevent the adoption of these simple, inexpensive and effective approaches to reducing these infections and in turn reducing the incidence of primary liver cancer.


How we are going to be able to get the benefits of this new drug to developing countries where it is most needed remains the unanswerable question.  This drug is expensive, and probably far beyond the means of those who need it most.


And that raises the larger issue that I have discussed previously, namely how are we going to be able to afford our miracles.


We need to develop a sustainable economic/business model that works for everyone: the companies that discover, market and manufacture these drugs; the insurers and governments who pay for the drugs; and, most importantly, the patients who need the drugs.


Finding a solution to that conundrum is, in my personal opinion, probably one of the most important issues we face in cancer treatment today.

14 thoughts on “Sorafenib:A New Treatment For Primary Liver Cancer

  1. hi dr len, my dad has recently been diagnosed with liver cancer. he currently resides in malaysia. i’m wondering how he can probably gain access to sorafenib?? i tried the company website without much luck.

    would u happen to know if there’s gonna be any trials being set up in the south east asian region? cuz really, it’ll be a real shame to miss out on sorafenib given the amazing results that’s bringing our hopes up.

    thanks, daisy

  2. Hello Daisy, Dr. Len regrets that he is not able to respond to individual requests regarding clinical trials. You may want to start with Also, please call our National Cancer Information Center (NCIC)at 1-800-ACS-2345 to get answers to questions about cancer-related issues. The NCIC is open 24 hours a day, 7 days a week.

  3. Hi Dr. Len, I appreciate your thoughtful summary of the ASCO sesion on Sorafenib. It is clear that this represents a breakgthrough in liver cancer treatment. However, many questions remain unanswered, e.g. whether Sorafenib will be safe in patients with advanced liver dysfunction (the majority of patients). I would also like to point you to a very comprehensive database on new drugs in oncology: . I hope you find this helpful. Henry

  4. Dr. Len. I am searching for information on treatments for hepatocellular cancer that is not in the liver but has metatisized to the lungs. Approx 6 years ago my niece had a liver tumor during preganancy in which small section was maglignant. That was removed and she has just recently had diagnosis of hepatocellular tumor in lung. One spot in lung (2.5) and potentially one lymph node outside the lung. These have shown up after second pregnancy. No other common factors. All information that I have found is concerning patients with advanced stage of liver cancer thru hepatitis or cirrohsis. She is a healthy 33 yr old with no other health issues. Can you provide any information that could help our search for treatments.

  5. Hello Michelle, our National Cancer Information Center (NCIC)at 1-800-ACS-2345 can help you get answers to questions about hepatocelluar cancer and other cancer-related issues. The NCIC is open 24 hours a day, 7 days a week.

  6. My father has to decide on sorafenib for his liver cancer. PET scans show that it is confined to the liver and is primary in nature. He is a diabetic with a history of congestive heart failure, renal failure and an insulin-dependent diabetic and 84 years old. How does this medication compare to any other technique? Specifically, to a “technique” that destroys blood vessels to the tumor?

  7. Cells are the most basic structure of the body. Cells make up tissues, and tissues make up organs, such as the lungs or liver. Each cell is surrounded by a membrane, a thin layer that separates the outside of the cell from the inside. For a cell to perform necessary functions for the body and respond to its surroundings, it needs to communicate with other cells in the body. Communication occurs through chemical messages in a process called signal transduction. The purpose of these signals is to tell the cell what to do, such as when to grow, divide into two new cells, and die. The “targets” that the new molecular drugs go after can be located on the “inside” or “outside” of a cancer cell. The most common targets on the outside are receptors, proteins that help relay chemical messages. And many targets on the inside are enzymes, proteins that help speed up chemical reactions in the body. What Nexavar, Iressa, Tarceva, Sutent and Tykerb have in common is that they are small molecule drugs. Exciting results have come from studies of multitargeted tyrosine kinase inhibitors, small molecules that act on multiple receptors in the cancerous cells. Targeted cancer therapies use drugs that block the growth and spread of cancer by interfering with specific molecules involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than current chemotherapy treatments, but not necessarily less toxic. So it doesn’t matter if there is a “target” molecule in the cell that the “targeted” drug is going after, if the drug either won’t “get in” in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, drug “resistance” is multifactorial, and could cause more toxicity. What may work in some patients, may not work in other patients. What’s good for the group may not be good for the individual, affirms that in the tactic of using “fresh” biopsied cells to predict which cancer treatments will work best for the individual patient, this or any other molecular drug has to get inside the cells in order to “target” anything. If a drug works extremely well for a certain percentage of cancer patients, identify which ones. If one drug or another is working for some people (not average populations) then obviously there are others out there who would also benefit. Drug sensitivity tests support the idea that a marginal benefit in terms of overall survival is observed in cancer patients with normal prognoses, but there are “marked survival benefits” for cancer patients with poor prognoses. What is needed is to sort out what’s the best profile in terms of which patients benefit from this drug or any other drug. Can they be combined? What’s the proper way to work with these new drugs? Each of these new targeted drugs are not for everybody. The study of cell function analysis tells us that even when the disease is the same type, different patients’ tumors respond differently to the same agents.

  8. Dr Len,
    My father was diagnosed in Sept 2005 with primary liver cancer. He died in January of 07. How and why he contracted this is driving me crazy. He never had hepatitis of any kind, rarely drank anything but red wine and even that only a few times a year. He had high cholesterol and had a heart attack in 1998. He had been on Zocor (80mg) since that time. Is there any direct link between the statin drugs and this type of cancer?
    I would sincerely appreciate any insight you may have.
    Thank you

  9. My husband has been on Nexavar for the last 7 months. He was diagnosed with primary liver cancer in November 2007. The cancer has disminished with about 10% on the ct-scans. He wasn’t and isn’t very well though. Unable to eat anything better than drinkable stuff like yoghurt, milkshakes, soups and the hated prosure/ensure. Nothing solid, not even bread. The moment his salivaru gland starrts working, het gets very sick and puking.His weight has dropped to 60 kilos, but he isn’t very large (1.65 m)and it is more or less stable now. He has had all the side-effects like blisters on hands and feet and he is mostly very tired.
    Any suggestions to liven him up are welcomed!

  10. My husband was given chronic HEP C in blood transfusions
    in the mid 90’s. In 2009, he was diagnosed with liver cancer. He was put on Nexavar and it did not work. It allowed the cancer to grow and begin to spread into his nodes in his stomach. We went to Yawkey Cancer Center in Boston,Mass to see Dr. Andrew Zhu. He recommended a clinical trial because the tumors on my husbands liver were very large and very involved, and he believed that the traditional chemo or radiation would not work. As long as my husband responds to treatment, he will live.
    This is so sad. But, I want to help others: IF YOU OR A LOVED ONE ARE DIAGNOSED WITH LIVER CANCER, RUN DO NOT WALK, TO YAWKEY CANCER CENTER IN BOSTON MASS.If you have any gastrointestinal cancer, go there! MAY GOD BLESS YOU.

  11. Has there been any research regarding immunotherapy vs chemo therapy for primary liver cancer.? My Aunt was recently diagnosed with advanced stage liver cancer and is being treated with Sorafenib but the side effects are horrible for her. I’ve recently heard of two different success stories with use of immunotherapy, inwhich the patients are now “cancer free”. I do not know what type of cancer these individuals were diagnosed with.

    Thank you.

    1. Your aunt should be seen at a center that does clinical research into the treatment of liver cancer (which sometimes can start in the liver, or spread from elsewhere in the body. The fact that she is on sorafenib suggests this was primary liver cancer). Our cancer information specialists at 800 227 2345 can help her find her center, however the best place to start for information would be with the team currently treating her. Immunotherapy has shown benefits in some cancers, but not all. Each situation is unique. However there may be other trials that she could consider.

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