Interactions of Herceptin® (trastuzumab) and Chemotherapeutic Agents
Interactions of Herceptin® (trastuzumab) and Chemotherapeutic Agents
Shortly after our team returned from ASCO in May, 2001, we summarized some information on the use of Herceptin® (trastuzumab) which was presented by Dr. Dennis Slamon of UCLA in an ASCO session on Sunday, 13 May 2001, in San Francisco. This information was also presented, with some additions, at a meeting of the Los Angeles Breast Cancer Alliance on Thursday, 20 June 2001. This essay does not contain information from other sources nor does it contain a description of the methods used to determine degree of synergy reported herein.
The important issue for patients is that some types of chemotherapeutic agents work better with Herceptin® than others and several have been found to be antagonistic when used with Herceptin. Additionally, radiation has been found to be profoundly synergistic.
Merriam-Webster shows synergistic as being derived from the Greek synergos which means working together. The Merriam-Webster definition in English is "a mutually advantageous conjunction or compatibility of distinct elements". In some sense, the idea is that for the synergistic chemos, 1 + 1 = something more 2 while for the antagonistic chemos, 1 + 1 = something less than 2.
In the context of patients' being treated for breast cancer with Herceptin®, this means that Herceptin® and the chosen chemotherapy should be given "together", meaning one immediately after the other, rather than the chosen chemotherapy being given in a series of cycles followed by Herceptin® given in a second series of cycles.
The information we have summarized is in the table below:
| Degree of synergy | Generic name | Brand (proprietary) name |
| Profoundly synergistic | Cisplatin
Carboplatin |
Platinol®, CDDP®
Paraplatin® |
| Synergistic | Docetaxel
Vinorelbine tartrate Vinblastine sulfate Etoposide |
Taxotere®
Navelbine® Velban® VP-16®, VePesid® |
| Additive | Pacletaxel
Gemcitabine Methotrexate sodium |
Taxol®
Gemzar® Methotrexate, Rheumatrex® |
| Antagonistic | 5-Fluorouracil
Capecitabine |
5-FU®, fluorouracil
Xeloda® |
| In addition to the chemotherapeutic agents listed above, radiation has been found to be profoundly synergistic with Herceptin® (trastuzumab). | ||
A related issue that has come up in discussions about the side effects of various chemotherapeutic agents, particularly when they are used with Herceptin®, is the matter of congestive heart failure (CHF) which sometimes occurs in patients who receive what are called anthracyline-containing regimens. Adriamycin (doxirubicin), Doxil (liposomal doxirubicin), and Ellence (epirubicin) are the primary anthracylines used to treat breast cancer.
From the data examined to date, it appears that not only does giving an anthracyline while receiving Herceptin® lead to an increased incidence of congestive heart failure, but also receiving Herceptin®after having received an anthracyline leads to an increased incidence of congestive heart failure. Two important points about this situation are:
Congestive heart failure (CHF) happens when a person's heart is not able to pump enough blood to get oxygen and glucose, among other things, out to the cells to properly nourish the cells. This also causes a back pressure in the lungs which may result in the buildup of fluid in the lungs,
At some point when they are being staged for treatment, most patients receive either a MUGA (multi-gated array) scan (see our list of abbreviations) or an echocardiogram as staging for their chemotherapy. Both of these tests tell the doctor what the patient's "ejection fraction" is. Sometimes this will be abbreviated as EF and sometimes as LVEF (the LV stands for left ventricular which is the bottom chamber on the left side of the patient's heart).
The LVEF is given in percentages based on the estimated amount of blood that the patient's heart should be pumping and for which the doctors have really good tables to figure out what it should be. In general, most incredibly fit people are often in the 70s while "regular" people are in the high 50s and in the 60s. It is very rare for oncologists to give additional chemotherapy containing anthracylines (the chemotherapeutic agents mentioned above) or Herceptin if the LVEF goes much below 50, except in unusual situations. The same applies to other medications that may cause CHF as a side effect.
One of the things that can be done to minimize anthracyline-related CHF is to give the patient Zinecard (or a similar cardio-protectant drug) along with the anthracycline, particularly if the LVEF starts showing up way before the patient gets near the lifetime limits of anthracylines. However, oncologists are debating whether patients who receive the cardio-protectant drug with their anthracyline may have a less effective result from their chemotherapy.
Characteristic symptoms of CHF are shortness of breath and retaining water. Shortness of breath is a fairly clear symptom of something's being wrong and should be checked out in any case. Retaining water may result in weight gain or puffiness in the legs (especially) or arms and should also be checked out with the patient's doctors.
WARNING: Not all shortness of breath is due to CHF. Neither is all water retention due to CHF. But, both conditions should be checked out with your doctors.
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