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Systemic Therapy

Photo of prescription pad with pills“Systemic therapy” refers to drugs that travel through the bloodstream to reach cancer cells throughout the body, and includes chemotherapy, targeted drugs and immunotherapy.

Chemotherapy kills all rapidly dividing cells, including tumors and normal cells in the blood, bone marrow, digestive tract and hair follicles. Depending on the particular drug, patients on chemotherapy may deal with a combination of fatigue, hair loss, depression of the immune system, nausea and damage to the heart, liver and kidneys. Targeted agents are drugs whose activity is intended to interfere with specific molecules involved in cancer progression. They may block cell growth signals, boost the immune system, stop the growth of blood vessels supporting tumors, deliver toxic drugs to cancer cells or fix cell processes that would normally suppress tumors. Typically, targeted agents are less toxic than chemotherapy. Immunotherapy encompasses various approaches to harnessing a patient’s immune system to attack tumor cells.

No systemic therapy has been approved by the U.S. Food and Drug Administration (FDA) for ACC because none has been effective yet across large groups of ACC patients. However, clearly-progressive ACC patients may have to resort to systemic therapy when dealing with growing tumors that are numerous or located near vital organs that are not treatable with surgery or radiation. Fortunately, there are many open clinical trials that are seeking better treatments for metastatic ACC patients.

Cancer is not one disease. Historically, tumor types were defined by location (breast, colon, lung, salivary glands, etc.) or by histology (the size, shape and patterns of tumor cells). The presumption was that the cause and response to any given treatment would be the same for each defined tumor group. However, the genomics revolution has shifted the framework, classifying tumors not only by location and histology, but also by the molecular pathways that drive a particular tumor. It turns out that there are many different ways in which tumors develop, even in the same location. Whereas all breast cancer patients used to cycle through the same chemotherapies, now they are divided into groups defined by how much estrogen, HER2 or other molecular targets are present in each tumor. Different targeted agents are prescribed according to the many different molecules that drive different cancers. By personalizing medicine, doctors are increasingly able to provide treatments to the patients who will benefit while sparing side effects and expenses for those who will not. Tumor profiling reports may be ordered by medical oncologists to help in selecting systemic therapies.

Since its inception, ACCRF has been organizing and supporting research to identify the molecular pathways that matter in ACC, the first step in trying to match patients with the appropriate targeted agents. A deeper understanding of the basic biology of ACC as well as preclinical drug screening in ACC animal models have permitted more promising clinical trials to move forward.

For the most current information on systemic therapies for ACC, refer to our review of past clinical trials at Completed Studies.

As the number of clinical trials and potential treatments for ACC patients has grown, medical oncologists are becoming more active in documenting their approaches to taking care of their patients. In 2021, the American Society of Clinical Oncology (ASCO) published its clinical guidelines for salivary gland cancer patients, including ACC. And at the end of 2022, the European Society for Medical Oncology (ESMO) published its similar clinical guidelines. In addition, the following journal articles focus more narrowly on ACC alone: