Jimmie C. Holland

Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B

PURPOSE Patients with high-risk myelodysplastic syndrome (MDS) have high mortality from bone marrow failure or transformation to acute leukemia. Supportive care is standard therapy. We previously reported that azacitidine (Aza C) was active in patients with high-risk MDS. PATIENTS AND METHODS A randomized controlled trial was undertaken in 191 patients with MDS to compare Aza C (75 mg/m(2)/d subcutaneously for 7 days every 28 days) with supportive care. MDS was defined by French-American-British criteria. New rigorous response criteria were applied. Both arms received transfusions and antibiotics as required. Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C. RESULTS Responses occurred in 60% of patients on the Aza C arm (7% complete response, 16% partial response, 37% improved) compared with 5% (improved) receiving supportive care (P <.001). Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care (P =.007). Transformation to acute myelogenous leukemia occurred as the first event in 15% of patients on the Aza C arm and in 38% receiving supportive care (P =.001). Eliminating the confounding effect of early cross-over to Aza C, a landmark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care (P =.03). Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to Aza C. CONCLUSION Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care. Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study.

Screening for psychologic distress in ambulatory cancer patients : A multicenter evaluation of the distress thermometer

Based on evidence that psychologic distress often goes unrecognized although it is common among cancer patients, clinical practice guidelines recommend routine screening for distress. For this study, the authors sought to determine whether the single‐item Distress Thermometer (DT) compared favorably with longer measures currently used to screen for distress.

Depression in hospitalized cancer patients.

&NA; The study of depression in cancer patients has been hampered by difficulty in establishing diagnostic criteria, since neurovegetative signs and symptoms may be attributable either to depression or physical illness. Confusion has also arisen in defining the boundary between “normal” grieving with illness, and “abnormal” clinical depression. We studied 62 oncology inpatients applying DSM‐III diagnostic criteria, patient self‐report, and interview report rating scales. Forty‐two percent met criteria for nonbipolar major depression: 24% with severe and 18% with moderately severe symptoms. Fourteen percent of the sample had depressive symptoms that did not meet criteria for a major depression. Forty‐four percent had no depressed affect. Medical and demographic variables were evaluated for relationship to depression; only greater degree of physical disability was clearly associated. Other negative life events and poor quality of social supports were additionally associated with depression in the less disabled patients. The use of clearly defined criteria for diagnosis of depression in cancer patients provides a basis for the study and implementation of specific therapeutic interventions.

Single-Agent Versus Combination Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The Cancer and Leukemia Group B (study 9730)

PURPOSE We compared the efficacy of combination chemotherapy versus single-agent therapy in patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS A total of 561 eligible patients were randomly assigned to receive paclitaxel alone or in combination with carboplatin. RESULTS The response rate was 17% in the paclitaxel arm and 30% in the carboplatin-paclitaxel arm (P < .0001). Median failure-free survival was 2.5 months in the paclitaxel arm and 4.6 months in the carboplatin-paclitaxel arm (P = .0002). Median survival times were 6.7 months (95% CI, 5.8 to 7.8) and 8.8 months (95% CI, 8.0 to 9.9), and 1-year survival rates were 32% (95% CI, 27% to 38%), and 37% (95% CI, 32% to 43%), respectively. The overall survival distributions were not statistically different: hazard ratio = 0.91 (95% CI, 0.77 to 1.17; P = .25). Hematological toxicity and nausea were more frequent in the combination arm, but febrile neutropenia and toxic deaths were equally low in both arms. There was no significant survival difference in elderly patients. Performance status 2 patients treated with combination chemotherapy had a better survival rate than those treated with single-agent therapy (P = .019). CONCLUSION Combination chemotherapy improves response rate and failure-free survival compared with single-agent therapy, but there was no statistically significant difference in the primary end point of overall survival. The results in elderly patients were similar to younger patients. Performance status 2 patients had a superior outcome when treated with combination chemotherapy.

Impact of Azacytidine on the Quality of Life of Patients With Myelodysplastic Syndrome Treated in a Randomized Phase III Trial: A Cancer and Leukemia Group B Study

PURPOSE The impact of azacytidine (Aza C) on the quality of life of 191 patients with myelodysplastic syndrome was assessed in a phase III Cancer and Leukemia Group B trial (9221). PATIENTS AND METHODS One hundred ninety-one patients (mean age, 67.5 years; 69% male) were randomized to receive either Aza C (75 mg/m(2) subcutaneous for 7 days every 4 weeks) or supportive care, with supportive care patients crossing over to Aza C upon disease progression. Quality of life was assessed by centrally conducted telephone interviews at baseline and days 50, 106, and 182. Overall quality of life, psychological state, and social functioning were assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the Mental Health Inventory (MHI). RESULTS Patients on the Aza C arm experienced significantly greater improvement in fatigue (EORTC, P =.001), dyspnea (EORTC, P =.0014), physical functioning (EORTC, P =.0002), positive affect (MHI, P =.0077), and psychological distress (MHI, P =.015) over the course of the study period than those in the supportive care arm. Particularly striking were improvements in fatigue and psychological state (MHI) in patients treated with Aza C compared with those receiving supportive care for patients who remained on study through at least day 106, corresponding to four cycles of Aza C. Significant differences between the two groups in quality of life were maintained even after controlling for the number of RBC transfusions. CONCLUSION Improved quality of life for patients treated with Aza C coupled with significantly greater treatment response and delayed time to transformation to acute myeloid leukemia or death compared with patients on supportive care (P <.001) establishes Aza C as an important treatment option for myelodysplastic syndrome.

Developing a cancer-specific geriatric assessment: A feasibility study

As the U.S. population ages, there is an emerging need to characterize the “functional age” of older patients with cancer to tailor treatment decisions and stratify outcomes based on factors other than chronologic age. The goals of the current study were to develop a brief, but comprehensive, primarily self‐administered cancer‐specific geriatric assessment measure and to determine its feasibility as measured by 1) the percentage of patients able to complete the measure on their own, 2) the length of time to complete, and 3) patient satisfaction with the measure.

Comparative studies of psychological function in patients with advanced cancer--I. Self-reported depressive symptoms.

&NA; Depressive symptoms assessed by the Beck Depression Inventory were compared in 97 cancer patients, 66 next‐of‐kin of cancer patients, and 99 physically healthy persons who attempted suicide. Less than a fourth of the cancer patients and a fifth of their next‐of‐kin but over half of the psychiatric patients were moderately or severely depressed. The two patient groups were indistinguishable in somatic depressive symptoms, both scoring higher then the next‐of‐kin. The cancer patients and the next‐of‐kin were indistinguishable in nonsomatic (psychological) depressive symptoms, both scoring lower than the suicide attempters. Younger patients reported more nonsomatic symptoms than older ones. Beck scores and nearness to death were not associated in 57 cancer patients who expired. Vegetative depressive symptoms in cancer patients may reflect advanced disease, but nonsomatic symptoms should be reason for psychiatric consultation.

Long-term adjustment of survivors of early-stage breast carcinoma, 20 years after adjuvant chemotherapy†

The long‐term impact of breast carcinoma and its treatment was assessed in 153 breast carcinoma survivors previously treated on a Phase III randomized trial (Cancer and Leukemia Group B [CALGB 7581]) a median of 20 years after entry to CALGB 7581.

The memorial pain assessment card. A valid instrument for the evaluation of cancer pain

Effective evaluation and treatment of cancer pain require valid and independent measurement of pain intensity, pain relief, and psychological distress. The Memorial Pain Assessment Card (MPAC) is a simple instrument designed to provide rapid evaluation of these subjective experiences. On the 8.5 by 11 inch card are printed the eight pain intensity descriptors, and three visual analog scales which measure pain intensity, pain relief, and mood. Experienced patients can complete it in less than 20 seconds. The authors administered the MPAC to 50 hospitalized cancer patients within 48 hours of referral to the Pain Service for inadequate pain control, together with standard measures: The McGill Pain Questionnaire, Profile of Mood States, Hamilton Depression Scale, and Zung Anxiety Scale. Correlational and multiple regression analyses revealed that the MPAC can distinguish pain intensity from pain relief and from general psychological distress, and it can provide multidimensional assessment that is practically equivalent to the full assessment battery. We conclude that the MPAC is valid and effective for clinical use, and recommend it for the assessment of individual patients, and as an outcome measure in clinical trials.

History of psycho-oncology: overcoming attitudinal and conceptual barriers.

The formal beginnings of psycho-oncology date to the mid-1970s, when the stigma making the word “cancer” unspeakable was diminished to the point that the diagnosis could be revealed and the feelings of patients about their illness could be explored for the first time. However, a second stigma has contributed to the late development of interest in the psychological dimensions of cancer: negative attitudes attached to mental illness and psychological problems, even in the context of medical illness. It is important to understand these historical underpinnings because they continue to color contemporary attitudes and beliefs about cancer and its psychiatric comorbidity and psychosocial problems. Over the last quarter of the past century, psycho-oncology became a subspecialty of oncology with its own body of knowledge contributing to cancer care. In the new millennium, a significant base of literature, training programs, and a broad research agenda have evolved with applications at all points on the cancer continuum: behavioral research in changing lifestyle and habits to reduce cancer risk; study of behaviors and attitudes to ensure early detection; study of psychological issues related to genetic risk and testing; symptom control (anxiety, depression, delirium, pain, and fatigue) during active treatment; management of psychological sequelae in cancer survivors; and management of the psychological aspects of palliative and end-of-life care. Links between psychological and physiological domains of relevance to cancer risk and survival are being actively explored through psychoneuroimmunology. Research in these areas will occupy the research agenda for the first quarter of the new century. At the start of the third millennium, psycho-oncology has come of age as one of the youngest subspecialties of oncology, as one of the most clearly defined subspecialties of consultation-liaison psychiatry, and as an example of the value of a broad multidisciplinary application of the behavioral and social sciences.