Phase I versus palliative care: striking the right balance.

DOI: 10.1200/JCO.2008.20.7803 Freireich and Kurzrock highlight the extraordinary promise of investigational therapies through two patient case presentations of a rare disease, known as “the disease with hope,” that accounts for just 0.62 patient cases per 100,000 person-years. They chose the patient cases of young, fit, and resourceful men diagnosed with hairy cell leukemia, years before effective therapies were available or known. Both of these individuals drew tremendous personal benefit from participating in early-phase clinical trials. The authors correctly ask the key question, “When is it too soon to abandon the prospects for a favorable outcome from investigational therapy?” They go on to note that many oncologists have dismissed the option of referring patients for investigational therapies because of a low likelihood of personal benefit. Even though they acknowledge that when a patient receives a “hopeless” diagnosis it is important for the physician to discuss palliative care, they emphasize the need to be “knowledgeable about...options for participating in clinical research at major research centers.” Oncologists are rightly trained to refer patients for whom there is no effective standard therapy to seek care at major cancer centers and explore the option of treatment on a clinical trial. All of us have rejoiced in the formidable breakthroughs in oncology and celebrate the discoveries of platinum compounds in the treatment of testicular cancer, or the great advances in the use of targeted therapies that help patients live longer and better quality lives. This is our passion. These anecdotes, however, do not address the harsher reality experienced by the vast majority of patients with advanced metastatic malignancy. It is important to acknowledge that solid epithelial cancers are, at present, different from hematologic malignancies. The more typical clinical scenario involves an individual with a solid tumor who has tried more than one chemotherapeutic regimen and has experienced little benefit and considerable toxicity in the process. The patient may, for many reasons, avoid asking the physician to explain his or her prognosis, even as the oncologist may be reluctant to provide details of expected outcomes. Physicians commonly fail to provide vital prognostic information as a result of multiple factors, including a lack of training in communication skills, and the perceived desire to avoid “removing hope.” Such patients are often more comfortable receiving treatment near home, and perhaps cannot afford a trip to a distant city for consideration of a novel treatment. For such individuals, having access to early palliative care represents an opportunity to maintain the hopes of avoiding undue toxicity and fulfilling whatever tasks are important as they near the end of their lives. Failure to prepare patients for death deprives them and their survivors of meaningful interactions that can never be replaced. Recent research shows quite clearly that talking about imminent death does not lead to despair or depression and allows for appropriate care near the end of life— avoiding futile chemotherapy, intubations, and hospitalizations, and leading to longer enrollment in hospice. Other research also shows clearly that patients who overestimate their prognosis do not live longer, but rather just have more chemotherapy, intubations, and deaths in the hospital. Honest communication between patients and their oncologists as to the underlying prognosis and the potential risks and benefits of standard or experimental therapies is essential to clarify goals and options specific to individual patients and their current circumstances. This serves to strengthen the therapeutic alliance. We need improved assessments that include a patient’s performance status, comorbid illnesses, goals and desires, and ability to understand the investigational nature and uncertain benefit of receiving treatment on an early-phase clinical trial. Oncologists need the skills to convey this information in a supportive and empathetic fashion, but also need to recognize when standard treatments no longer hold any promise of improved outcome, be it cure, longevity, or symptom relief. Addressing opportunities for treatment on early-phase clinical trials should be part of routine conversations between eligible cancer patients and their physicians. Ideally, referrals should be made as early as possible in the course of the disease, and not in the last weeks of life. JOURNAL OF CLINICAL ONCOLOGY T H E A R T O F O N C O L O G Y: When the Tumor Is Not the Target VOLUME 27 NUMBER 2 JANUARY 1