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    California Pacific Currents 2000

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    Oncology Clinical Trials: Key to New Cancer Therapies

    Although oncology clinical research is the key to improving cancer therapies, only about 3% of American adults with cancer enroll in clinical trials. Patients who fear becoming “guinea pigs” avoid participation. Some believe they will receive placebo when treatment is warranted. Additionally, many health care institutions lack access to protocols as well as dedicated staff to enroll patients and collect data.

    California Pacific Medical Center and the Research Institute have improved on this statistic. “In the last two years, enrollment in oncology clinical trials has tripled,” says Kathleen Grant, MD, chief of the division of Medical Oncology and Hematology. “The medical center and the research institute are directing more resources toward clinical research and have hired research coordinator Tess McGinn, who assists us with patient enrollment. Physician enthusiasm is increasing, and patients — savvy about emerging treatments — frequently request protocol therapy.”

    Physicians at California Pacific participate in National Cancer Institute (NCI) and pharmaceutical industry-sponsored studies through the Sutter Health Western Division Cancer Research Group, of which Grant serves as co-principal investigator. “Additionally, some California Pacific oncologists develop their own protocols, and others serve as principal investigators for industry-sponsored trials,” comments McGinn. “We now have over 70 oncology clinical trials available to our adult patients.”

    Lynne Day, manager of clinical research, adds, “With the closing of Mount Zion, several oncologists have joined our medical staff, expanding the availability of cancer protocols. The research institute, through its clinical trials office, is dedicated to supporting this effort.”

    Regulating Doses to Find the Most Effective Therapy
    Oncology clinical trials often use approved treatments but test different doses or new therapy combinations. In some instances, says Daniel Glaubiger, MD, chair of the department of Radiation Oncology, more may be better. He cites the ablation of malignant bone marrow cells followed by stem cell rescue for some leukemias. “But in situations with more favorable outcomes, like Hodgkin's disease, we study treatments with reduced doses, in order to maintain positive results while minimizing morbidity.”

    Identifying appropriate doses is also a challenge in hormonal therapy for prostate cancer, according to urologist Ira Sharlip, MD. The cornerstone of prostate cancer therapy is a combination of drugs that decrease levels of male hormones, which, if uncontrolled, may stimulate cancer growth. “We are completing one trial that compares different doses of an anti-androgen, as well as another trial studying a new agent,” notes Dr. Sharlip.

    Dr. Glaubiger and his colleague, Roy Abendroth, MD, observe that technology drives advances in radiation oncology. “We are currently upgrading to the newest equipment, which will allow us to participate in increasing numbers of clinical trials,” says Dr. Glaubiger.

    Other significant breakthroughs, explains medical oncologist Ari Baron, MD, are occurring with novel classes of agents like angiogenesis inhibitors, which block the development of new blood vessels. The rationale is to cut off the supply of oxygen and nutrients to the tumor, thereby limiting cancer growth and metastasis. “We have an ongoing study treating lung cancer with a matrix metalloproteinase inhibitor, and we hope to initiate a trial using vascular endothelial growth factor (VEGF) for colon cancer.”

    Medical oncologist David Minor, MD, shares Dr. Baron's interest. His protocol evaluating the effectiveness of the angiogenesis inhibitor thalidomide in the treatment of metastatic renal cell cancer was presented to the American Society of Clinical Oncology in May, 2000. Since thalidomide can cause serious birth defects, it is never given to pregnant women.

    Dr. Minor's colleague Alan Kramer, MD, is writing a protocol that adds VEGF to standard chemotherapy for metastatic breast cancer, which he hopes to initiate with the National Surgical Adjuvant Breast and Bowel Project, a cooperative group of the NCI. “In addition to these kinds of studies,” Dr. Kramer comments, “our community should develop links between basic science research and clinical trials.”

    Dr. Abendroth agrees. “As our understanding of the genetic basis of malignancy advances, we should explore how basic science can be translated into clinical research, and, ultimately, new treatment strategies.”

    Helping Those at High Risk
    “Another trend in cancer research,” says medical oncologist Bertrand Tuan, MD, “is cancer prevention.” California Pacific investigators recently completed a study using a retinoid, which is a Vitamin A-like compound, to prevent head and neck cancer recurrence. Two other prevention trials are in progress. The first compares
    tamoxifen, an approved breast cancer therapy, to raloxifene, a drug used to treat osteoporosis, in postmenopausal women at high risk for breast cancer. In the second, selenium is being studied in men with benign prostatic intraepithelial neoplasia, a condition which may be a precursor to prostate cancer.

    Pediatric Oncology Clinical Research
    Medical and radiation oncologists may struggle to enroll adult patients in research studies, but fully 80% of pediatric oncology patients are enrolled in clinical trials nationwide. Most receive treatment at pediatric oncology centers that are affiliated with one of two NCI-sponsored cooperative groups.

    Access to pediatric trials has been limited at California Pacific in recent years, according to Joan Battaini, RN, research coordinator for pediatric oncology. In response, Yung Yim, MD, medical director for the Sutter Children's Center Pediatric Oncology Group, and pediatric oncology colleagues Kent Jolly, MD and Yisheng Lee, MD, PhD, are bringing California Pacific on board.

    “Sutter is a full member of an NCI cooperative group and has a well-established pediatric oncology program,” says Dr. Yim. “Currently, the two national cooperative groups are merging to form the Children's Oncology Group (COG). By October 2000, California Pacific patients will have access to COG's full range of pediatric oncology clinical trials.”

    Pediatric cancer research is concentrated in the common childhood cancers such as leukemia, lymphoma, brain tumors, and other solid tumors. “We study approved chemotherapy and radiation therapy used in new ways,” says Dr. Yim, “and we look at new agents. It is more difficult obtaining approval for drugs such as angiogenesis inhibitors for the pediatric population, although some may become available for brain cancer research.”

    Dr. Lee describes the department's objectives. “We hope to complement the excellent children's cancer programs in the Bay Area. We envision a northern California-wide program that delivers patient-friendly service while providing comprehensive access to clinical trials.” The goal is to improve treatment outcomes while maintaining quality of life.

    Dr. Kathleen Grant shares her pediatric oncology counterparts' enthusiasm. “As we redefine the current best cancer therapies, communities that lack access to protocols look to research institutions like California Pacific to set new treatment standards.”

    Monitoring the Informed Consent Process
    Clinical trials, and much of drug development, would not be possible without the scores of patients who elect to be research volunteers. It is the job of the Institutional Review Board (IRB) to protect the rights of research volunteers. “The main focus for the IRB,” says Lynne Day, manager of Clinical Research, “is to ensure that patients receive the information they need to make a free and informed decision about their participation in research.”

    As the volume of clinical trials at the medical center continues to grow, and the regulatory burden on clinical research increases, how does an IRB monitor the informed consent process in a manner that does not violate patient confidentiality? Day and Paige Wycoff, IRB coordinator, in collaboration with Stuart Dick, MPH, RD, outcomes research specialist, developed a short, nine-question, anonymous survey to be completed by research volunteers.

    Patients are asked to respond to questions that assess how well they understand their role as a research volunteer and to provide information about how they experienced the informed consent process. Periodic monitoring of survey results will help guide the IRB and clinical research administration to focus efforts on areas that are not being well served in the consent process. “The survey tool fits nicely into the IRB's ongoing educational program for members, clinical investigators, and staff,” says Wycoff.