Test All Chemo Patients for Hepatitis B, Says NCCN Presenter

[Guest guest]

http://www.medscape.com/viewarticle/739169

From Medscape Medical News > Oncology

Test All Chemo Patients for Hepatitis B, Says NCCN Presenter

Nick Mulcahy

March 17, 2011 (Hollywood, Florida) ¡ª Every cancer patient undergoing

chemotherapy should be tested for hepatitis B virus (HBV) infection, said a

presenter here at the National Comprehensive Cancer Network (NCCN) 16th Annual

Conference.

Chemotherapy and its related immunosuppression can cause a reactivation of HBV

¨C " a potentially fatal and preventable disease, " said Emmy Ludwig, MD, from

Memorial Sloan-Kettering Cancer Center in New York City.

" Reactivation may complicate cancer therapy, " said Dr. Ludwig, explaining that

delays in treatment can result.

Testing allows infected patients ¡ª those with chronic infection or past

exposure ¡ª to be treated with prophylactic antiviral oral therapy, which is an

" extremely effective " means of preventing reactivation, she said. Dr. Ludwig

also told the NCCN audience that 5% to 40% of reactivation cases will die of

liver failure.

Currently, cancer patients treated with rituximab are routinely screened for

HBV, said Dr. Ludwig. In 2004, the US Food and Drug Administration issued a

warning that there was a risk for HBV-reactivation-related fatal fulminant

hepatitis with rituximab.

However, the need to screen for HBV is often associated only with " high-risk "

groups, said Dr. Ludwig, especially natives of Asia. But " profiling patients by

country of birth misses patients ¡ª about half of them, " she said.

Furthermore, she said that the HBV problem is " enormous " and that an estimated

one third of the world has been " exposed " to HBV, meaning that they have a core

antibody (HBcAb+), and that about 350 million people have chronic infection,

meaning that they have a surface antigen (HBsAg+).

In the United States, an estimated 15 million people (5% of population) have

been exposed and about 1 million have chronic infection.

Interestingly, the NCCN does not recommend universal testing for patients

undergoing chemotherapy.

Instead, the NCCN says in its Prevention and Treatment of Cancer-Related

Infections guideline, that, " in patients undergoing intensive immunosuppressive

therapy, evaluation of HBV surface antigen, core antibody, and surface antibody

should be considered at baseline. " Patients with a surface antibody only

(HBsAb+) are effectively immunized against HBV, noted Dr. Ludwig.

The NCCN also recommends evaluation in hematopoietic stem cell transplantation

recipients and donors.

However, at least 2 NCCN institutions routinely test all chemotherapy patients

for HBV. Memorial Sloan-Kettering does, said Dr. Ludwig. Their testing protocol

was outlined at the American Society of Clinical Oncology (ASCO) 2010 Annual

Meeting.

Stanford Comprehensive Cancer Center in Palo Alto, California, also tests for

HBV, Carlson, MD, told Medscape Medical News. Dr. Carlson is a breast

cancer expert from Stanford who attended the NCCN meeting.

Another meeting attendee, Suzanne Cole, MD, from ton, West Virginia, was

inspired by Dr. Ludwig's presentation. " I plan to personally screen all patients

I am placing on chemotherapy for hepatitis B, " she told Medscape Medical News.

" It is not difficult or expensive to screen for patients at risk for

reactivation ¡ª I currently screen everyone who receives rituximab chemotherapy

for hepatitis B, " she added.

Dr. Cole also said that her group at the ton Area Medical Center might

perform an observational study " to see how many patients we identify at risk for

hep B reactivation. "

" I hope we see more data emerge on the true risk of hepatitis B reactivation

during chemotherapy, " she said.

Dr. Ludwig said that the hepatitis C virus (HCV) is not comparable to the B

virus with regard to activation. Immunosuppression from chemotherapy can

increase HCV RNA levels, but related flares are " rare " and are " not

preventable, " she said.

Limited Data

The NCCN guideline says that the data are " limited " in support of antiviral

therapy for active HBV infection in the context of cancer treatment.

Dr. Ludwig said that the data in support of prophylaxis have " major

limitations. " She cited a systematic review of 14 studies (2 randomized

controlled trials, 8 prospective cohort studies, 4 retrospective cohort

studies). Despite various shortcomings, the data collectively indicated that

none of the patients in the studies receiving prophylactic lamivudine developed

HBV©\related hepatic failure (0 of 108 patients vs 21 of 162 patients who

received placebo).

The options for HBV treatment include lamivudine (which is no longer in favor

because of drug-resistant viral mutations that occur with long-term therapy),

entecavir (which is used at Memorial Sloan-Kettering), adefovir, tenofovir, and

telbivudine.

Also, prevention is better than treatment after reactivation, according to the

results of one study, said Dr. Ludwig.

In that study, 30 HBsAg+ lymphoma patients were randomized to either lamivudine

treatment before chemotherapy (prophylaxis) or lamivudine treatment during

chemotherapy if HBV DNA polymerase chain reaction levels increased. There was no

HBV reactivation in the prophylaxis group, but in the delayed treatment group,

53% reactivated. Furthermore, there was no HBV acute hepatitis or liver failure

in the prophylaxis group, whereas there was 47% in the delayed treatment group.

" Screening and prophylaxis appear to work, " said Dr. Ludwig.

A number of organizations endorse universal screening for immunosuppressive

therapy. The list includes the American Association for the Study of Liver

Diseases, the European Association for the Study of the Liver, the American

Gastroenterology Association, the World Gastroenterology Organization, the

Asian©\Pacific Association for the Study of the Liver, the American College of

Rheumatology, the Infectious Disease Society of America, the French Society of

Rheumatology, and the Centers for Disease Control and Prevention.

ASCO does not recommend universal screening and says that randomized controlled

trials are needed to establish reactivation rates and HBV-related complications,

said Dr. Ludwig.

Dr. Ludwig argued that such trials might not be possible, that " other evidence

of effectiveness is good, " and that the potential benefits are " large. "

" There are no randomized controlled trials to show that parachutes work, " she

argued.

Since instituting screening at Memorial Sloan-Kettering in 2006, the center has

had only 3 reactivations, all of which were related to a failure to adhere to

the treatment, said Dr. Ludwig.

National Comprehensive Cancer Network (NCCN) 16th Annual Conference. Presented

March 10, 2011.

Authors and Disclosures

Journalist

Nick Mulcahy

Nick Mulcahy is a senior journalist for Medscape Hematology-Oncology. Before

joining Medscape, Nick was a freelance medical news writer for 15 years, working

for companies such as the International Medical News Group, MedPage Today,

HealthDay, McMahon Publishing, and Advanstar. He is also the former managing

editor of breastcancer.org. He can be contacted at nmulcahy@....

[Guest guest]

http://www.medscape.com/viewarticle/739169

From Medscape Medical News > Oncology

Test All Chemo Patients for Hepatitis B, Says NCCN Presenter

Nick Mulcahy

March 17, 2011 (Hollywood, Florida) ¡ª Every cancer patient undergoing

chemotherapy should be tested for hepatitis B virus (HBV) infection, said a

presenter here at the National Comprehensive Cancer Network (NCCN) 16th Annual

Conference.

Chemotherapy and its related immunosuppression can cause a reactivation of HBV

¨C " a potentially fatal and preventable disease, " said Emmy Ludwig, MD, from

Memorial Sloan-Kettering Cancer Center in New York City.

" Reactivation may complicate cancer therapy, " said Dr. Ludwig, explaining that

delays in treatment can result.

Testing allows infected patients ¡ª those with chronic infection or past

exposure ¡ª to be treated with prophylactic antiviral oral therapy, which is an

" extremely effective " means of preventing reactivation, she said. Dr. Ludwig

also told the NCCN audience that 5% to 40% of reactivation cases will die of

liver failure.

Currently, cancer patients treated with rituximab are routinely screened for

HBV, said Dr. Ludwig. In 2004, the US Food and Drug Administration issued a

warning that there was a risk for HBV-reactivation-related fatal fulminant

hepatitis with rituximab.

However, the need to screen for HBV is often associated only with " high-risk "

groups, said Dr. Ludwig, especially natives of Asia. But " profiling patients by

country of birth misses patients ¡ª about half of them, " she said.

Furthermore, she said that the HBV problem is " enormous " and that an estimated

one third of the world has been " exposed " to HBV, meaning that they have a core

antibody (HBcAb+), and that about 350 million people have chronic infection,

meaning that they have a surface antigen (HBsAg+).

In the United States, an estimated 15 million people (5% of population) have

been exposed and about 1 million have chronic infection.

Interestingly, the NCCN does not recommend universal testing for patients

undergoing chemotherapy.

Instead, the NCCN says in its Prevention and Treatment of Cancer-Related

Infections guideline, that, " in patients undergoing intensive immunosuppressive

therapy, evaluation of HBV surface antigen, core antibody, and surface antibody

should be considered at baseline. " Patients with a surface antibody only

(HBsAb+) are effectively immunized against HBV, noted Dr. Ludwig.

The NCCN also recommends evaluation in hematopoietic stem cell transplantation

recipients and donors.

However, at least 2 NCCN institutions routinely test all chemotherapy patients

for HBV. Memorial Sloan-Kettering does, said Dr. Ludwig. Their testing protocol

was outlined at the American Society of Clinical Oncology (ASCO) 2010 Annual

Meeting.

Stanford Comprehensive Cancer Center in Palo Alto, California, also tests for

HBV, Carlson, MD, told Medscape Medical News. Dr. Carlson is a breast

cancer expert from Stanford who attended the NCCN meeting.

Another meeting attendee, Suzanne Cole, MD, from ton, West Virginia, was

inspired by Dr. Ludwig's presentation. " I plan to personally screen all patients

I am placing on chemotherapy for hepatitis B, " she told Medscape Medical News.

" It is not difficult or expensive to screen for patients at risk for

reactivation ¡ª I currently screen everyone who receives rituximab chemotherapy

for hepatitis B, " she added.

Dr. Cole also said that her group at the ton Area Medical Center might

perform an observational study " to see how many patients we identify at risk for

hep B reactivation. "

" I hope we see more data emerge on the true risk of hepatitis B reactivation

during chemotherapy, " she said.

Dr. Ludwig said that the hepatitis C virus (HCV) is not comparable to the B

virus with regard to activation. Immunosuppression from chemotherapy can

increase HCV RNA levels, but related flares are " rare " and are " not

preventable, " she said.

Limited Data

The NCCN guideline says that the data are " limited " in support of antiviral

therapy for active HBV infection in the context of cancer treatment.

Dr. Ludwig said that the data in support of prophylaxis have " major

limitations. " She cited a systematic review of 14 studies (2 randomized

controlled trials, 8 prospective cohort studies, 4 retrospective cohort

studies). Despite various shortcomings, the data collectively indicated that

none of the patients in the studies receiving prophylactic lamivudine developed

HBV©\related hepatic failure (0 of 108 patients vs 21 of 162 patients who

received placebo).

The options for HBV treatment include lamivudine (which is no longer in favor

because of drug-resistant viral mutations that occur with long-term therapy),

entecavir (which is used at Memorial Sloan-Kettering), adefovir, tenofovir, and

telbivudine.

Also, prevention is better than treatment after reactivation, according to the

results of one study, said Dr. Ludwig.

In that study, 30 HBsAg+ lymphoma patients were randomized to either lamivudine

treatment before chemotherapy (prophylaxis) or lamivudine treatment during

chemotherapy if HBV DNA polymerase chain reaction levels increased. There was no

HBV reactivation in the prophylaxis group, but in the delayed treatment group,

53% reactivated. Furthermore, there was no HBV acute hepatitis or liver failure

in the prophylaxis group, whereas there was 47% in the delayed treatment group.

" Screening and prophylaxis appear to work, " said Dr. Ludwig.

A number of organizations endorse universal screening for immunosuppressive

therapy. The list includes the American Association for the Study of Liver

Diseases, the European Association for the Study of the Liver, the American

Gastroenterology Association, the World Gastroenterology Organization, the

Asian©\Pacific Association for the Study of the Liver, the American College of

Rheumatology, the Infectious Disease Society of America, the French Society of

Rheumatology, and the Centers for Disease Control and Prevention.

ASCO does not recommend universal screening and says that randomized controlled

trials are needed to establish reactivation rates and HBV-related complications,

said Dr. Ludwig.

Dr. Ludwig argued that such trials might not be possible, that " other evidence

of effectiveness is good, " and that the potential benefits are " large. "

" There are no randomized controlled trials to show that parachutes work, " she

argued.

Since instituting screening at Memorial Sloan-Kettering in 2006, the center has

had only 3 reactivations, all of which were related to a failure to adhere to

the treatment, said Dr. Ludwig.

National Comprehensive Cancer Network (NCCN) 16th Annual Conference. Presented

March 10, 2011.

Authors and Disclosures

Journalist

Nick Mulcahy

Nick Mulcahy is a senior journalist for Medscape Hematology-Oncology. Before

joining Medscape, Nick was a freelance medical news writer for 15 years, working

for companies such as the International Medical News Group, MedPage Today,

HealthDay, McMahon Publishing, and Advanstar. He is also the former managing

editor of breastcancer.org. He can be contacted at nmulcahy@....