A promising new melanoma liver cancer treatment directs therapy directly at the liver. The procedure, percutaneous hepatic perfusion, or PHP, targets tumors with a dose of chemotherapy 10 times stronger than patients could tolerate intravenously. Doctors use a specially designed system of catheters and filters to apply the cancer-fighting drug only to the liver, reducing the risk of damaging nearby organs and minimizing possible side effects.

The liver is resilient and unlike other organs can tolerate large amounts of chemotherapy. It is one of the largest organs in the body and is essential for general health. The liver removes harmful material from the blood, aids in digestion of food and converts food into nutrients for a healthy and active life. However, cancer can severely impair the liver's ability to perform these crucial functions, and often times when cancer originates in or spreads to the liver, the tumors in the liver can lead to death. When cancer originates in the liver it is called primary liver cancer. Cancer that has spread to the liver from other parts of the body is called secondary, or metastatic, cancer in the liver.

Doctors say PHP is an important step because people who have melanoma liver cancer usually don't live very long. Slightly fewer than 70,000 new cases of this type of cancer will be diagnosed this year in the United States, according to the American Cancer Society. Although it is not the most common of all skin cancers, it is the most deadly. Ocular melanoma is much rarer, with about 2,500 new cases detected each year. The cancer is often lethal if it spreads to the liver, which is the most common site for it to metastasize.

During the procedure, patients receive doses of a drug called melphalan for 30 minutes every four weeks. The treatment takes place in an operating room while the patient is under an anesthetic. The chemo drug is delivered by a catheter that is threaded up a major artery in the patient's groin into the main artery that goes into the liver. Another catheter is placed in the major vein behind the liver, and balloons on the catheter are inflated to direct all the blood flowing out of the liver into a filter outside the body. This filter system removes almost 90 percent of the chemotherapy from the blood, and the blood is then given back to the patient through a catheter placed in a large vein in the neck.

For more information on the clinical trial please see: http://www.livercancertrials.com/

Labels: cancer, clinical trials, Liver, melanoma, percutaneous, php

On June 11, 2009, the FDA altered healthcare professionals a clinical trial suggests sirolimus may be associated with an increased morality rate. The study compared the mortality rate of stable liver transplant patients who converted from a calcineurin inhibitor (CNI)-based immunosuppressive regimen to sirolimus (Rapamune) to those who remained on a CNI regimen.

The trial was conducted by sirolimus’ manufacturer, Wyeth. After one year, the overall treatment failure rates were significantly higher for the patients converted to sirolimus compared to those that continued on CNIs. Treatment failure is measured by the occurrence of acute rejection or premature discontinuation for any reason. Patients on sirolimus discontinued its use due to an adverse event more often than CNI patients. Sirolimus’s most frequent adverse events were peripheral edema, stomatitis, rash, and mouth ulceration.

Currently, Sirolimus is approved for treating prophylaxis of organ rejection in patients aged 13 years or older receiving kidney transplants. The safety and efficacy of this drug in liver or lung transplant patients have not been established by the FDA.

The current Boxed Warning of sirolimus indicates that the use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant patients. Many of these patients had evidence of infection at or near the time of death.

The FDA is examining this information and will make the appropriate recommendations. The FDA is determining whether a labeling change for sirolimus is needed. In the interim, physicians should continue to use the drug’s professional labeling as a guide to therapy.

At this time, FDA has not made any changes to the professional label for sirolimus.
Any adverse events associated with Sirolimus should be reported to the FDA.

The FDA can be contacted via:
Online at www.fda.gov/medwatch/report.htm
Phone at 1-800-FDA-1088
Fax at 1-800-FDA-0178, using the MedWatch Form 3500
(available at www.fda.gov/medwatch/ getforms.htm)
Mail, using the postage-paid MedWatch Form 3500 (see above), to MedWatch, 5600
Fishers Lane, Rockville, MD 20852-9787
For information please see: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm165015.htm

Labels: CNI, death, kidney failure, Liver, Rapamune, sirolimus, transplant, Wyeth

Propylthiouracil (PTU) treats hyperthyroidism (including Graves disease) by decreasing the amount of thyroid hormone produced by the thyroid gland. Its notable side effects include a risk of agranulocytosis. Agranulocytosis is a rare, drug-induced blood disorder that is characterized by a severe reduction in the number of white blood cells in the circulating blood.

Propylthiouracil is only available in the United States as a generic medication. Some manufacturers include Actavis Elizabeth, LLC of New Jersey and West-Ward Pharmaceutical Corp, also, of New Jersey.

Recently on June 3, 2009, the FDA alerted healthcare professionals of the seriousness of hepatic reactions related to PTU. It poses a risk of serious liver injury, including liver failure and death in adult and pediatric patients.

Reports to FDA’s Adverse Event Reporting System suggest there is an increased risk of hepatotoxicity with PTU when compared to methimazole. Metimazole is another treatment option for thyroid disorders. FDA has identified 32 cases (22 adult and 10 pediatric) of serious liver injury associated with PTU use. Although both PTU and Metimazole are treatments of hyperthyroidism due to Graves’ disease, healthcare professionals should carefully consider which drug to initiate in a patient recently diagnosed with Graves’ disease.

Physicians should closely monitor patients on PTU therapy for symptoms and signs of liver injury, especially during the first six months of treatment.

PTU should not be used in pediatric patients as a last resort. The FDA suggests that PTU only be used in pediatric patients who are allergic to or intolerant of Metimazole, and there are no other treatment options available.

West-Ward’s label from September 2007 does warn of agranulocytosis and of severe hepatic reactions. It is generally perceived the treatment of hyperthyroidism and not the disease itself causes these serious side effects.

Reports of adverse events associated with Propylthiouracil, including liver failure, should be reported to the FDA.


The FDA can be contacted via:
Online at www.fda.gov/medwatch/report.htm
Phone at 1-800-FDA-1088
Fax at 1-800-FDA-0178, using the MedWatch Form 3500
(available at www.fda.gov/medwatch/ getforms.htm)
Mail, using the postage-paid MedWatch Form 3500 (see above), to MedWatch, 5600
Fishers Lane, Rockville, MD 20852-9787

For more information please see: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm

Labels: children, death, FDA, hepatic, Liver, PTU

On April 16, 2009, the Drug Safety Oversight Board briefly discussed orlistat and the potential risk of hepatotoxicity.

Orlistat is the active ingredient in anti-obesity drugs such as the prescription drug Xenical and the over-the-counter drug Alli.

Xenical is manufactured by Roche, which is headquartered in Nutley, N.J. Alli is manufactured GlaxoSmithKline, which is headquartered in England.

Sue Sutter of Scrip News in her May 21, 2009 article "US FDA examining reports of liver damage with orlistat" gives more details on the relationship between Orlistat and hepatotoxicity.

"Orlistat was discussed in the context of both non-prescription and prescription versions and the potential risk of hepatotoxicity based on several post marketing reports," the FDA told Scrip.

The agency said it was still reviewing the case reports to determine the extent of orlistat's contribution, if any, to the development of liver damage. The FDA declined to provide the number of post marketing reports it has received and said any action would depend upon results of its ongoing analysis....

Roche said more than 35 million patients have been exposed to orlistat therapy, and obesity is a high risk factor for hepatic injury. "The available information – post marketing spontaneous reports, clinical trial data and published literature as well as epidemiology data for drug-induced liver disease – does not suggest that orlistat is causally related to hepatic events."

Currently in Xenical’s package insert there are only rare reports of hepatic, or liver, injury.

The FDA has investigated Orlistat over concerns of rectal bleeding. See: Potential Signals of Serious Risks/New Safety Information Identified from the Adverse Event Reporting System (AERS) between April - June 2008

Any adverse reactions, such as hepatitis, liver injury or liver failure experienced with the use of Xenical or Alli should be reported to the FDA’s MedWatch Program

by phone at 1-800-FDA-1088,
by fax at 1-800-FDA-0178,
by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787,
or on the MedWatch website at www.fda.gov/medwatch.

Labels: Alli, FDA, hepatic, Hepatotoxicity, Liver, MedWatch, Orlistat, Xenical