how does herceptin affect the heart?!
Question: I had a MUGA scan that dropped from 60% to 48%
Answers:
Here is an excerpt from the warning letter sent to physicians from the manufacturer of Herceptin:
"Dear Healthcare Provider:
Genentech, Inc. wishes to inform you of updated cardiotoxicity information related to the use of HERCEPTIN® (trastuzumab), obtained from the National Surgical Adjuvant Breast and Bowel Project (NSABP) study (B-31), a randomized, Phase III trial that was conducted in 2043 women with operable, HER2 overexpressing breast cancer (IHC 3+ or FISH+).
This study demonstrated a significant increase in cardiotoxicity in patients who were randomized to the HERCEPTIN-containing arm as compared to patients who received chemotherapy alone.
A preliminary analysis of the safety data from Study NSABP B-31 was presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in May 2005, during the presentation of a joint analysis of Study NSABP B-31 and the North Central Cancer Treatment Group (NCCTG) study (N9831). Study NSABP B-31 was intended, in part, to characterize cardiotoxicity associated with HERCEPTIN use and to assess the value of serial cardiac monitoring during HERCEPTIN therapy as a predictor of cardiotoxicity and as an aid to early identification of cardiac toxicity.
Study NSABP B-31 evaluated the addition of HERCEPTIN to standard adjuvant chemotherapy. The chemotherapy regimen
consisted of four cycles of doxorubicin and cyclophosphamide (AC) followed by four cycles of paclitaxel every 3 weeks; patients were randomized to receive 1 year of HERCEPTIN, at the approved dose and schedule, during and following paclitaxel (Arm 2) or to paclitaxel alone (Arm 1). Patients in this study were required to have a baseline assessment of cardiac function with either multigated acquisition scan (MUGA) or echocardiogram and to have follow-up assessments at the completion of AC and at 6, 9, and 18 months after the initiation of paclitaxel with or without HERCEPTIN.
Eligible patients had a left ventricular ejection fraction (LVEF) measurement at baseline (prior to any therapy) that was within normal limits and no history of or active cardiac disease, including cardiomyopathy, congestive heart failure, prior myocardial infarction, or arrhythmia.
Prior to initiation of HERCEPTIN (Arm 2), LVEF measurements were required to be at or above the radiology facility's lower limit of normal (LLN) and be no more than 15 points below baseline measurements.
For patients randomized to Arm 2 with asymptomatic decrease in LVEF, the following table lists the guidelines that were employed for dose modification of HERCEPTIN [table unable to be produced here].
HERCEPTIN was permanently discontinued in patients with symptomatic cardiac toxicity. In the event that HERCEPTlN
administration was withheld or discontinued because of cardiotoxicity, paclitaxel was administered at the investigator's discretion.
A total of 1019 patients were randomized to the HERCEPTIN-containing arm (Arm 2). Based on preliminary data and analyses through April 2005, 6.8% of patients were unable to initiate HERCEPTlN per the protocol because of decreased LVEF or symptoms of cardiac toxicity experienced during the AC portion of therapy. Among the evaluable patients who had adequate cardiac function and initiated HERCEPTIN, 30.5% required at least one dose delay because of asymptomatic decrease in LVEF or cardiac symptoms.
In 18.6% of patients, HERCEPTIN was discontinued prior to the completion of 1 year of therapy because of asymptomatic decrease in LVEF (14.3%) and symptomatic cardiac dysfunction/other cardiac toxicity (4.3%).
In addition, a statistically significant increase in the 3-year cumulative incidence of New York Heart Association Class III and IV congestive heart failure and cardiac death was observed in patients who received the HERCEPTIN-containing regimen (4.1%) compared with control (0.8%).
There were no cardiac deaths observed in patients who received the HERCEPTIN-containing regimen and 1 cardiac death was observed in the control arm.
Final analysis of the cardiac safety data collected in Studies NSABP B-31 and NCCTG N9831 is ongoing.
Risk factors for cardiac dysfunction will be analyzed with data from both the NSABP B-31 and NCCTG N9831 trials, when
available. A preliminary exploratory analysis performed by NSABP investigators suggests that age and LVEF following AC
chemotherapy may identify patients at greatest risk for symptomatic cardiac dysfunction.
Should you need any further information on HERCEPTIN-related cardiotoxicity, please contact our Medical Communication Department at 1-800-821-8590 or at the “Contact Us” section of the Genentech corporate website
(http://www.gene.com/gene/contact/).
Healthcare professionals should report any serious adverse events suspected to be associated with the use of HERCEPTIN to Genentech at 1-888-835-2555. Alternately, this information may also be reported to the FDA's MedWatch reporting system by telephone (1-800-FDA-1088), facsimile (1-800-FDA-0178), online (https://www.accessdata.fda.gov/scripts/medwatch/)," title="https://www.accessdata.fda.gov/scripts/medwatch/),">https://www.accessdata.fda.gov/scripts/m. or
mailed, using the MedWatch form FDA 3500 to the FDA Medical Products Reporting Program, 5600 Fishers Lane, Rockville,
MD 20852-9787."
There is an additional warning on Genentech's site that states:
"Treatment with Herceptin has been associated with cardiac dysfunction, severe hypersensitivity reactions (including anaphylaxis), infusion reactions, and pulmonary events. Rarely, these have been fatal.(1)
In clinical trials, the incidence and severity of cardiac dysfunction was highest in patients receiving Herceptin in combination with anthracyclines and cyclophosphamide.(1) Most patients responded to medical therapy, including discontinuation of Herceptin. However, some patients were successfully managed while continuing Herceptin therapy.(3) Patients receiving Herceptin should be monitored for deteriorating cardiac function.(1)
In clinical trials, approximately 40% of patients experienced symptoms such as chills and fever during the first infusion. These and other symptoms, including nausea, vomiting, and pain, occurred infrequently with subsequent infusions.(1)
In clinical trials, the incidence of moderate to severe neutropenia and of febrile neutropenia was higher in patients receiving Herceptin plus myelosuppressive chemotherapy versus chemotherapy alone.(1)
There was an increased incidence of anemia, leukopenia, diarrhea, and infection when Herceptin was used in combination with chemotherapy.(1)"
The full prescribing info, which states in part that "HERCEPTIN administration can result in the development of ventricular dysfunction and congestive heart failure. Left ventricular function should be evaluated in all patients prior to and during treatment with HERCEPTIN. Discontinuation of HERCEPTIN treatment should be strongly considered in patients who develop a clinically significant decrease in left ventricular function. The incidence and severity of cardiac dysfunction was particularly high in patients who received HERCEPTIN in combination with anthracyclines and cyclophosphamide," is available online at:
http://www.gene.com/gene/products/information/oncology/herceptin/insert.jsp
Hope that helps, and good luck to you.
Answers: