Perioperative Medicine Summit

SCOTTSDALE, ARIZ. – Patients on targeted cancer therapies require special handling in the perioperative period, according to oncologist Sunil K. Sahai.

In addition to the known cardiotoxic side effects of DNA-damaging chemotherapy drugs such as anthracyclines and alkylating agents, newer drugs directed toward specific molecular targets on cancerous tumors have their own side effects that can complicate surgery or recovery, said Dr. Sahai of the University of Texas M.D. Anderson Cancer Center in Houston.

It can be a challenge even for oncologists to stay current with new cancer therapies and their side effect profiles, Dr. Sahai said at a meeting on perioperative medicine sponsored by the University of Miami.

"When M.D. Anderson was founded in the 1940s as the Texas Tumor Institute, there were three chemotherapy drugs on the market. Last year our formulary had 150 different chemotherapy drugs, " he said.

There are four major classes of targeted agents, each with its own associated adverse effects:

• Selective estrogen receptor modulators, such as tamoxifen and toremifene.

• Aromatase inhibitors – letrozole, anastrozole, and exemestane.

• Monoclonal antibodies – cetuximab, bevacizumab, trastuzumab, and others.

• Tyrosine kinase inhibitors (TKIs) – imatinib, dasatinib, sunitinib, and others.

Dr. Sahai presented case examples to illustrate the challenges of perioperative management of patients on targeted therapies. When a 67-year-old morbidly obese woman taking tamoxifen for the prevention of breast cancer presents with acute cholecystitis requiring urgent laparoscopic surgery, for example, Dr. Sahai said he would recommend 30 days of postoperative low-molecular-weight heparin injections to prevent venous thromboembolic events (VTEs).

"Patients who are on tamoxifen have a [baseline] relative risk of a VTE of between 3 and 7," he noted.

The combination of tamoxifen, obesity, and a history of breast cancer in a patient undergoing abdominal surgery suggests a high risk for VTE and a need for prophylaxis, he said.

He said he would not, however, recommend stopping tamoxifen without a documented discussion between the oncologist and the patient.

"Most oncologists are okay with stopping tamoxifen for 5-7 days during a procedure, but most of them are not willing to go for more than 14 days of stopping it," he said.

There are no data to support the practice; rather, it’s a matter of personal preference, he added.

Cardiotoxic agents

The cardiotoxic effects of older chemotherapy agents such as the anthracycline doxorubicin are well known, but newer agents, such as the monoclonal antibody trastuzumab (Herceptin) also have documented cardiotoxicities, although their long-term effects will not be known until the drugs have been on the market longer, Dr. Sahai pointed out.

Thus, a patient with colorectal cancer treated with an anthracycline is at increased risk for cardiomyopathy and heart failure, and if he receives a monoclonal antibody, he is at increased risk for ischemic cardiomyopathy. The combination of an anthracycline and trastuzumab (also used to treat gastric cancers) can increase the risk for heart failure by up to 28%, Dr. Sahai noted.

He also advised his colleagues to monitor patients receiving TKIs (most frequently prescribed for hematologic malignancies) for cardiac rhythm disturbances and drug interactions.

TKIs can prolong the QTc interval, predisposing patients to torsades de pointes, a form of ventricular tachycardia that can cause sudden death.

In addition, TKIs can cause pleural effusions, and are associated with difficult-to-control hypertension, Dr. Sahai said.

Decisions, decisions

If patients treated for cancer present for evaluation before noncardiac surgery with symptoms of cardiovascular disease such as chest pain, shortness of breath, or dyspnea on exertion, the clinician should first determine whether the symptoms appeared before, during, or after cancer therapy.

If the symptoms appeared before treatment, the patients should be evaluated for cardiovascular disease according to 2007 American College of Cardiology/American Heart Association perioperative evaluation guidelines, Dr. Sahai said.

If the cancer therapy included radiation or chemotherapy known to have cardiovascular side effects, patients should be tested for conditions that are most likely associated with their treatment history, whether myocardial ischemia, cardiomyopathies, arrhythmias, valvular disease, or a combination, he advised.

Dr. Sahai reported having no relevant financial disclosures.

SCOTTSDALE, ARIZ. – Patients on targeted cancer therapies require special handling in the perioperative period, according to oncologist Sunil K. Sahai.

In addition to the known cardiotoxic side effects of DNA-damaging chemotherapy drugs such as anthracyclines and alkylating agents, newer drugs directed toward specific molecular targets on cancerous tumors have their own side effects that can complicate surgery or recovery, said Dr. Sahai of the University of Texas M.D. Anderson Cancer Center in Houston.

It can be a challenge even for oncologists to stay current with new cancer therapies and their side effect profiles, Dr. Sahai said at a meeting on perioperative medicine sponsored by the University of Miami.

"When M.D. Anderson was founded in the 1940s as the Texas Tumor Institute, there were three chemotherapy drugs on the market. Last year our formulary had 150 different chemotherapy drugs, " he said.

There are four major classes of targeted agents, each with its own associated adverse effects:

• Selective estrogen receptor modulators, such as tamoxifen and toremifene.

• Aromatase inhibitors – letrozole, anastrozole, and exemestane.

• Monoclonal antibodies – cetuximab, bevacizumab, trastuzumab, and others.

• Tyrosine kinase inhibitors (TKIs) – imatinib, dasatinib, sunitinib, and others.

Dr. Sahai presented case examples to illustrate the challenges of perioperative management of patients on targeted therapies. When a 67-year-old morbidly obese woman taking tamoxifen for the prevention of breast cancer presents with acute cholecystitis requiring urgent laparoscopic surgery, for example, Dr. Sahai said he would recommend 30 days of postoperative low-molecular-weight heparin injections to prevent venous thromboembolic events (VTEs).

"Patients who are on tamoxifen have a [baseline] relative risk of a VTE of between 3 and 7," he noted.

The combination of tamoxifen, obesity, and a history of breast cancer in a patient undergoing abdominal surgery suggests a high risk for VTE and a need for prophylaxis, he said.

He said he would not, however, recommend stopping tamoxifen without a documented discussion between the oncologist and the patient.

"Most oncologists are okay with stopping tamoxifen for 5-7 days during a procedure, but most of them are not willing to go for more than 14 days of stopping it," he said.

There are no data to support the practice; rather, it’s a matter of personal preference, he added.

Cardiotoxic agents

The cardiotoxic effects of older chemotherapy agents such as the anthracycline doxorubicin are well known, but newer agents, such as the monoclonal antibody trastuzumab (Herceptin) also have documented cardiotoxicities, although their long-term effects will not be known until the drugs have been on the market longer, Dr. Sahai pointed out.

Thus, a patient with colorectal cancer treated with an anthracycline is at increased risk for cardiomyopathy and heart failure, and if he receives a monoclonal antibody, he is at increased risk for ischemic cardiomyopathy. The combination of an anthracycline and trastuzumab (also used to treat gastric cancers) can increase the risk for heart failure by up to 28%, Dr. Sahai noted.

He also advised his colleagues to monitor patients receiving TKIs (most frequently prescribed for hematologic malignancies) for cardiac rhythm disturbances and drug interactions.

TKIs can prolong the QTc interval, predisposing patients to torsades de pointes, a form of ventricular tachycardia that can cause sudden death.

In addition, TKIs can cause pleural effusions, and are associated with difficult-to-control hypertension, Dr. Sahai said.

Decisions, decisions

If patients treated for cancer present for evaluation before noncardiac surgery with symptoms of cardiovascular disease such as chest pain, shortness of breath, or dyspnea on exertion, the clinician should first determine whether the symptoms appeared before, during, or after cancer therapy.

If the symptoms appeared before treatment, the patients should be evaluated for cardiovascular disease according to 2007 American College of Cardiology/American Heart Association perioperative evaluation guidelines, Dr. Sahai said.

If the cancer therapy included radiation or chemotherapy known to have cardiovascular side effects, patients should be tested for conditions that are most likely associated with their treatment history, whether myocardial ischemia, cardiomyopathies, arrhythmias, valvular disease, or a combination, he advised.

Dr. Sahai reported having no relevant financial disclosures.

SCOTTSDALE, ARIZ. – Patients on targeted cancer therapies require special handling in the perioperative period, according to oncologist Sunil K. Sahai.

In addition to the known cardiotoxic side effects of DNA-damaging chemotherapy drugs such as anthracyclines and alkylating agents, newer drugs directed toward specific molecular targets on cancerous tumors have their own side effects that can complicate surgery or recovery, said Dr. Sahai of the University of Texas M.D. Anderson Cancer Center in Houston.

It can be a challenge even for oncologists to stay current with new cancer therapies and their side effect profiles, Dr. Sahai said at a meeting on perioperative medicine sponsored by the University of Miami.

"When M.D. Anderson was founded in the 1940s as the Texas Tumor Institute, there were three chemotherapy drugs on the market. Last year our formulary had 150 different chemotherapy drugs, " he said.

There are four major classes of targeted agents, each with its own associated adverse effects:

• Selective estrogen receptor modulators, such as tamoxifen and toremifene.

• Aromatase inhibitors – letrozole, anastrozole, and exemestane.

• Monoclonal antibodies – cetuximab, bevacizumab, trastuzumab, and others.

• Tyrosine kinase inhibitors (TKIs) – imatinib, dasatinib, sunitinib, and others.

Dr. Sahai presented case examples to illustrate the challenges of perioperative management of patients on targeted therapies. When a 67-year-old morbidly obese woman taking tamoxifen for the prevention of breast cancer presents with acute cholecystitis requiring urgent laparoscopic surgery, for example, Dr. Sahai said he would recommend 30 days of postoperative low-molecular-weight heparin injections to prevent venous thromboembolic events (VTEs).

"Patients who are on tamoxifen have a [baseline] relative risk of a VTE of between 3 and 7," he noted.

The combination of tamoxifen, obesity, and a history of breast cancer in a patient undergoing abdominal surgery suggests a high risk for VTE and a need for prophylaxis, he said.

He said he would not, however, recommend stopping tamoxifen without a documented discussion between the oncologist and the patient.

"Most oncologists are okay with stopping tamoxifen for 5-7 days during a procedure, but most of them are not willing to go for more than 14 days of stopping it," he said.

There are no data to support the practice; rather, it’s a matter of personal preference, he added.

Cardiotoxic agents

The cardiotoxic effects of older chemotherapy agents such as the anthracycline doxorubicin are well known, but newer agents, such as the monoclonal antibody trastuzumab (Herceptin) also have documented cardiotoxicities, although their long-term effects will not be known until the drugs have been on the market longer, Dr. Sahai pointed out.

Thus, a patient with colorectal cancer treated with an anthracycline is at increased risk for cardiomyopathy and heart failure, and if he receives a monoclonal antibody, he is at increased risk for ischemic cardiomyopathy. The combination of an anthracycline and trastuzumab (also used to treat gastric cancers) can increase the risk for heart failure by up to 28%, Dr. Sahai noted.

He also advised his colleagues to monitor patients receiving TKIs (most frequently prescribed for hematologic malignancies) for cardiac rhythm disturbances and drug interactions.

TKIs can prolong the QTc interval, predisposing patients to torsades de pointes, a form of ventricular tachycardia that can cause sudden death.

In addition, TKIs can cause pleural effusions, and are associated with difficult-to-control hypertension, Dr. Sahai said.

Decisions, decisions

If patients treated for cancer present for evaluation before noncardiac surgery with symptoms of cardiovascular disease such as chest pain, shortness of breath, or dyspnea on exertion, the clinician should first determine whether the symptoms appeared before, during, or after cancer therapy.

If the symptoms appeared before treatment, the patients should be evaluated for cardiovascular disease according to 2007 American College of Cardiology/American Heart Association perioperative evaluation guidelines, Dr. Sahai said.

If the cancer therapy included radiation or chemotherapy known to have cardiovascular side effects, patients should be tested for conditions that are most likely associated with their treatment history, whether myocardial ischemia, cardiomyopathies, arrhythmias, valvular disease, or a combination, he advised.

Dr. Sahai reported having no relevant financial disclosures.