Expert Viewpoint: William J. Gradishar, MD

Professor, Division of Hematology and Medical Oncology
Northwestern University
The Feinberg School of Medicine
Chicago, IL

William J. Gradishar, MD, is Professor of Medicine in the Division of Hematology and Medical Oncology at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois, and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. He also serves as director of Breast Medical Oncology, associate director of the Lynn Sage Comprehensive Breast Program, and program director of Northwestern University's Hematology/Oncology Fellowship Training Program. His research focuses on the development of novel therapeutics for the treatment of breast cancer. WebMD spoke recently with Dr. Gradishar about treatment options in patients with metastatic breast cancer previously untreated with chemotherapy. Specifically, Dr. Gradishar reviewed the factors in determining treatment regimens and the potential benefits of combination chemotherapy for appropriate patients. Following is a summary of this discussion.

WebMD: What are the primary factors that you consider when designing a treatment plan for patients with metastatic breast cancer who have not yet received chemotherapy in the metastatic setting (ie, those who may have received adjuvant chemotherapy and are not eligible for hormonal therapy either because they are hormonal receptor negative or refractory to hormonal therapy)?

DR. GRADISHAR: We look at each patient individually, of course. We look at the characteristics of their disease - hormone receptor positivity and HER-2 positivity. We take into account the extent of their disease, how much prior therapy they may have had in the adjuvant setting, and whether or not it included a taxane. We also take into account the interval from the completion of adjuvant therapy to the onset of metastatic disease. And, of course, we take into account the age of the patient, patient preferences, and their overall performance status. And we try and integrate those factors into making a decision.

In patients who have metastatic disease that is relatively endocrine-responsive, we may elect for those patients to preferentially use endocrine therapy until they're refractory. If they're not candidates for endocrine therapy, either because of the absence of estrogen receptor (ER) or progestin receptor (PR) positivity or they've become refractory to endocrine therapy, or they have bulky disease, where you only have one opportunity to really get a response, then we choose chemotherapy.

WebMD: What key patient and disease characteristics indicate poor prognosis in patients with metastatic disease?

DR. GRADISHAR: The things we think about are bulky, multi-organ involvement, ER-negative disease, patients who have what might be viewed as rapidly progressing disease, defined by a short interval from the time of the completion of their adjuvant therapy. And, to a certain degree, how much prior therapy they've had, as an indicator of potentially resistant disease.

WebMD: How does the presence of these factors influence your decisions about treatment?

DR. GRADISHAR: If a patient is ER negative, obviously it drives us towards chemotherapy. If they're HER-2 negative, it drives us towards therapeutic options that don't include trastuzumab. If a patient, you know, 3 months ago, completed their taxane-based chemotherapy, I may not necessarily choose as my first treatment choice to give them a taxane again.

If you have somebody that has extensive disease, you want to utilize whatever you think is going to have the highest probability of success. And most of the data today suggests that combination therapy is probably somewhat better than single-agent therapy in achieving that result.

WebMD: What do recent results with gemcitabine/paclitaxel(GT) show about the efficacy of this combination in patients with visceral metastases, lung and liver involvement, and progression within 6 months of adjuvant therapy?

DR. GRADISHAR: Clinical trials, including gemcitabine/paclitaxel versus single-agent paclitaxel, show the superiority of combination therapy, with better response rates, better times to disease progression, and probably improvements in overall survival. Combination gemcitabine/paclitaxel, although there is somewhat higher hematologic toxicity, is otherwise fairly similar to giving single-agent paclitaxel when you look at nonhematologic toxicity. So, it has a generally manageable toxicity profile. When considering combinations, GT is an appropriate therapy, because it is an effective therapy.

There are also data as to whether or not there are preferential sites of disease where therapies may or may not work. The data from the pivotal trial of GT versus paclitaxel alone have suggested that, regardless of whether a patient has visceral-dominant disease or not, or whether it's lung predominant or liver predominant, the GT combination is superior to single-agent therapy. And if you look at patients who developed metastatic disease less than versus more than 6 months from the time of completion of their adjuvant therapy, there remains an advantage for the GT regimen over paclitaxel.

WebMD: In patients who are appropriate for combination chemotherapy, what are the primary factors you use to determine the choice of agents?

DR. GRADISHAR: If you have things that are effective, but also at the same time have manageable toxicity profiles that would certainly rise to the top of your list of choices.

There are a lot of options for treating metastatic breast cancer with chemotherapy, both single-agent and combination therapy, and if one were choosing a combination regimen, the GT regimen would certainly be viewed as a standard that is a good treatment option due to its efficacy and safety profile.

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