Cancer Outcomes Research: A New Frontier
The Journal of the National Cancer Institute (JNCI) recently published Cancer Outcomes Research: The Arenas of Application. This monograph describes and evaluates the peer-reviewed literature in cancer outcomes research, identifies recent key contributions, and highlights challenges in applying scientific evidence to cancer care decision making. It also includes an assessment of the state of the science by NCI scientists and a discussion of future directions in this field.
Cancer outcomes research describes, interprets, and predicts the impact of interventions and other influences on final outcomes important to decision makers, including patients, clinicians, and policymakers. The monograph focuses on such patient-reported outcomes as health-related quality of life, perceptions of and satisfaction with health care, and the economic burden of cancer and its interventions, rather than more traditional outcomes such as survival and disease-free survival.
The monograph details how outcomes research enhances the knowledge base required for cancer care decision making and focuses on three areas of outcomes measurement: the macro-, meso-, and micro-levels. Macro-level studies explore trends in cancer-related outcomes and progress against cancer at the population level to inform policy and research. Meso-level studies include descriptive and analytical studies to better understand and improve cancer outcomes. Results of these studies influence decision making by patients, families, providers, payers, and organizations concerning safety, efficacy, and cost-effectiveness. Micro-level studies use patient-reported outcomes to improve patient-clinician communication and decision making and the overall quality of cancer care.
St. John's wort, an over-the-counter treatment for depression, can cause unwanted side effects in cancer patients who are taking imatinib mesylate (Gleevec), according to a study in the October 2004 Clinical Pharmacology & Therapeutics. Researchers at the University of Pittsburgh and the University of Florida found that the plant derivative sped up imatinib metabolism and its removal from the blood by 44 percent, thereby weakening the standard and effective dose.
The study, funded in part by NCI, involved 12 healthy subjects between the ages of 20 and 51. They received 400 mg of imatinib on day 1 of the study, 300 mg of St. John's wort three times a day on days 4 through 17, and 400 mg of imatinib on day 15. After each dose of imatinib, serial blood samples were taken over a period of 72 hours to measure the drug's clearance from the blood stream.
Because of wide use of complementary and alternative medicines among cancer patients, the authors note that their results could have dire implications for patients on imatinib: Because the dose of imatinib in patients with chronic myelogenous leukemia is directly related to their response, St. John's wort could lead to treatment failure. "Concomitant use of any drugs that [stimulate CYP3A4]" - the liver enzyme that metabolizes imatinib - "may necessitate an increase in the imatinib dose to achieve therapeutic concentrations and to maintain clinical effectiveness," they wrote.
A particular type of stem cell may be an effective delivery vehicle for anticancer agents, targeting tumor cells while sparing healthy tissues, researchers from M.D. Anderson Cancer Center report. The researchers, funded in part by NCI, modified mesenchymal stem cells (MSCs) to carry interferon beta (IFN-β), a biologic agent that promotes cell death and slows tumor cell growth, but that is typically toxic at the levels needed to achieve these effects in patients. Intravenous delivery of these modified MSCs (MSC-IFN-β cells) in xenograft mouse models of breast cancer and melanoma prevented lung metastases and significantly extended survival compared with untreated control mice, the researchers reported in the November 3 JNCI. Treatment with standard IFN-β failed to prolong survival in either model.
The researchers noted several limitations of this use of MSCs. For example, although the researchers found no evidence of MSC-IFN-β cells engrafting in healthy tissues, because MSCs target wound sites, infused MSC-IFN-β cells could potentially engraft in any tissues that have been injured by recent surgery or other mechanisms. They advised that human clinical trials testing MSCs as targeted delivery agents should "exclude patients who have undergone surgery or invasive procedures or have had infections."