Enhancing Quality of Life an Important Treatment Endpoint

VIENNA, Austria—When cure or prolongation of survival is no longer a reasonable possibility, enhancing the cancer patient’s quality of life becomes the preeminent objective of treatment, Ian Tannock, MD, of the Princess Margaret Hospital, Toronto, said at the 10^th European Cancer Conference (ECCO 10). “Quality of life is not a soft endpoint and, when measured appropriately, is every bit as reproducible as so-called objective measures such as tumor response,” he said.

Dr. Tannock challenged the tendency of clinical trials to concentrate on the endpoints of tumor response and survival, even in advanced metastatic disease where improvement in survival is unlikely. “If the goal of treatment is palliation, we should try to measure palliation directly,” he said.

Tumor response is not an endpoint of benefit to the patient, Dr. Tannock argued, noting that response may reflect patient selection, performance status, selection of response criteria, errors in measurement, and other methodologic issues. “If we shrink the patient as rapidly as we shrink the tumor, we haven’t gained much,” he said.

There are certain principles about measuring quality of life, he said, “and my own bias is that, in most clinical trials, including some of those that are still ongoing, it is done extremely badly.” He stressed that quality of life must be assessed not by physicians or family members but, rather, by patients themselves.

Dr. Tannock also criticized trials that compare mean quality of life at baseline with mean quality of life at a fixed point after randomization and then compare the mean changes between the two treatment arms.

In contrast, he said, clinical investigators measure tumor size for each patient at baseline, specify an a priori reduction in size and duration for which it must be maintained in order for a patient to be designated a responder, and then calculate the proportion of patients in each study arm who satisfy these criteria.

“Surely the analogy is the same with quality of life—it is an individual property of the patient,” Dr. Tannock said. “You have to measure a predefined quality of life for each patient at baseline and decide which quality of life endpoint is relevant. You specify a priori improvement in quality of life and the duration for which it must be maintained in order for the patient to have a palliative response. You measure quality of life repeatedly and determine the proportion of patients in each arm who satisfy the criteria and for how long.”

Dr. Tannock suggested that this approach could be applied in studies of hormone-refractory prostate cancer, where chemotherapy may well decrease PSA or improve bone scans while at the same time worsening quality of life. He and his colleagues have validated a simple, disease-specific questionnaire called PROSQOLI (Health-Related Quality of Life Instrument for Prostate Cancer), which consists of a six-point present pain intensity scale; an analgesic diary; and linear analog scales that measure pain, physical activity, fatigue, walking, appetite, constipation, and urination.

Using this instrument, the investigators found that prednisone plus mitoxan-trone (Novantrone) was superior to prednisone alone in either decreasing the pain score by at least 2 points or permitting a decrease in analgesic dose without increased pain, and that the combination produced a longer duration of response.

“We did not generate a pain improvement at the expense of other aspects of quality of life,” Dr. Tannock said, citing positive changes in the linear analog scales. Importantly, a substantial number of patients experienced an improvement in quality of life despite a rise in PSA levels or, conversely, showed no palliative response despite a fall in PSA.