Peter C. Trask

Phase II Study of Axitinib in Sorafenib-Refractory Metastatic Renal Cell Carcinoma

PURPOSE To investigate the efficacy and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 in patients with metastatic renal cell carcinoma (mRCC) refractory to prior therapies that included, but were not limited to, sorafenib. PATIENTS AND METHODS In this multicenter, open-label, phase II study, patients with sorafenib-refractory mRCC received a starting dose of axitinib 5 mg orally twice daily. A one-arm, single-stage design was used to estimate the primary end point of objective response rate (ORR), defined by RECIST (Response Evaluation Criteria in Solid Tumors). Secondary end points included safety, duration of response, progression-free survival (PFS), overall survival (OS), and patient-reported outcomes. RESULTS Of 62 patients recruited, 100% had received prior sorafenib, and 74.2% had received two or more prior systemic treatments. The axitinib dose was titrated to greater than 5 mg twice daily in 53.2% of patients, and 35.5% of patients had the dose modified to less than 5 mg twice daily. In 62 patients evaluable for response, the ORR was 22.6%, and the median duration of response was 17.5 months. Median PFS and OS times were 7.4 months (95% CI, 6.7 to 11.0 months) and 13.6 months (95% CI, 8.4 to 18.8 months), respectively. All-causality grade 3 to 4 adverse events included hand-foot syndrome (16.1%), fatigue (16.1%), hypertension (16.1%), dyspnea (14.5%), diarrhea (14.5%), dehydration (8.1%), and hypotension (6.5%). CONCLUSION Axitinib has antitumor activity in patients with mRCC refractory to prior VEGF-targeted therapy, including sorafenib. Toxicities were mild to moderate and were manageable. A randomized, phase III trial to compare axitinib with sorafenib in patients who have mRCC refractory to one prior first-line therapy regimen is underway.

Psychiatric Side Effects of Interferon Therapy: Prevalence, Proposed Mechanisms, and Future Directions

The increasing use of interferon (IFN) in treating a variety of disorders including, malignant melanoma and hepatitis C, has resulted in the identification and increasing concern about the psychiatric side effects that can result from treatment. These effects can occur either shortly after beginning IFN therapy or later as a result of continued treatment. Studies have reported the incidence of later side effects, which include symptoms of depression, anxiety, and occasional suicidal ideation, to be from 0% to 70%. Case studies have demonstrated that pharmacologic interventions are beneficial in reducing iatrogenic psychiatric symptoms while allowing patients to maintain IFN therapy. The present article provides an overview of the psychiatric effects of IFN therapy, the proposed mechanisms of these side effects, and case studies that provide mechanistic support. In addition, limitations of the current literature are provided with suggestions for treating physicians and a discussion of possible future research directions.

Psychosocial Characteristics of Individuals With Non–Stage IV Melanoma

PURPOSE Melanoma is the fastest growing solid tumor among men and women and accounts for 79% of skin cancer-related deaths. Research has identified that distress is frequently associated with a diagnosis of cancer and may slow treatment-seeking and recovery, increasing morbidity and even mortality through faster disease course. Given that the 5-year survival rates for individuals with melanoma are determined primarily by the depth and extent of spread, distress that interferes with seeking treatment has the potential to be life-threatening. PATIENTS AND METHODS The current study was designed to identify levels of distress present in individuals seeking treatment at a large, Midwestern, multidisciplinary melanoma clinic. It also focused on determining the quality of life, level of anxiety, and coping strategies used by individuals with melanoma before treatment. Given that the course of treatment and outcome for patients with stage IV disease is vastly different from that of patients with stages I to III disease, they were excluded from the study. RESULTS Results indicated that most individuals who are presenting to a melanoma clinic do not report a clinically significant level of distress. However, there is some variability in this, with 29% of patients reporting moderate to high levels of distress. Moreover, analyses suggest that distressed individuals are more likely to use maladaptive coping strategies, such as escape-avoidance coping, and to have poorer quality of life. CONCLUSION Although most individuals do not present with significant levels of distress, a significant minority are distressed and rely more heavily on coping strategies that do not benefit them. Such individuals would likely benefit most from psychological intervention.

Ruminating and Distracting: The Effects of Sequential Tasks on Depressed Mood

Response styles theory (Nolen-Hoeksema, 1987)provided the impetus for recent research effortsinvestigating the effects of rumination and distractionon depressed mood. This study elaborates on previous research by examining the sequential effects ofengaging in ruminating and distracting tasks. Resultsfrom two studies indicated that initially engaging in aruminating task maintained postinduction levels of dysphoric mood, whereas initially engagingin a distracting task reduced levels of dysphoric mood.More important, however, were the effects of task orderon mood. When participants engaged in a distracting taskfollowing aruminating task, dysphoric mood, which had been maintainedwith a ruminating task, was reduced to premoodinductionlevels. Of equal importance, individuals who ruminatedafter distracting maintained their current mood and did not report an increase in depressedmood. In the second study, engaging in sequentialrumination tasks further prolonged depressed mood,whereas engaging in sequential distraction tasks reduceddepressed mood. The results suggest that, althoughengaging in a rumination task maintains depressed moodand engaging in a distraction task reduces it, the orderin which these tasks are performed is also important. The implications of these results for responsestyles theory are discussed.

Personality predictors of mortality in cardiac transplant candidates and recipients

OBJECTIVES Emotional factors are generally recognized as impacting the care of end-stage heart disease and mortality following cardiac transplants. Equally important, however, are predictors of pretransplant mortality. The current study examined the utility of the Millon Behavioral Health Inventory (MBHI) as a predictor of pre- and posttransplant mortality. METHODS A total of 103 cardiac transplant candidates were assessed with the MBHI as part of a pretransplant evaluation that included baseline demographic variables and cardiac status. Time to transplant and mortality status at 1 and 5 years was also obtained. RESULTS Cluster analysis of MBHI response scores elicited two clusters characterized by high and low distress. Cluster membership predicted survival status at 1-year and 5-year follow-up, with high distress cluster patients having significantly higher mortality in both the total sample and a subgroup of patients who did receive a heart transplant. CONCLUSIONS These results support the value of the MBHI for assessing personality attributes that may dispose toward unfavorable outcome in heart transplant candidates. Further understanding of psychosocial contributions to illness course and outcome may enable more effective selection of treatment interventions with cardiac patients.

Understanding Chest Pain: What Every Psychologist Should Know

Chest pain is one of the most frequent presenting complaints in Emergency Rooms and other medical settings. A considerable number of these patients do not have significant coronary artery disease. This led to plausible alternative explanations for these presenting symptoms and these patients tend to have unremarkable cardiac outcomes. Nevertheless, many studies have also documented that symptoms and related disability persist in the face of reassurances about benign cardiac status. Given the implied threat of chest pain (e.g., myocardial infarction) and the presence of chest pain symptoms in other noncardiac conditions (including anxiety and panic), it is not surprising that many of these patients present with considerable emotional distress. Consequently, chest pain symptoms represent diagnostic and treatment dilemmas for physicians and psychologists alike. The extent to which cardiac and noncardiac factors contribute to all forms of chest pain remains unknown. The function of this review is to provide mental health professionals with a primer on relevant clinical issues in chronic chest pain. We examine several common medical and psychiatric causes of chronic chest pain and selectively review (1) the relevant medical and psychiatric diagnostic and treatment considerations for chest pain and (2) the hypothetical biobehavioral mechanisms relevant to psychological intervention, (3) while expanding on existing conceptual models for understanding chest pain, and (4) offering some suggestions for future research.

An exercise in cost-effectiveness analysis: Treating emotional distress in melanoma patients

This study presents a retrospective assessment of a psychological intervention examined for its potential cost-effectiveness if implemented into standard care. It discusses (1) the cost of instituting a psychological intervention for distressed melanoma patients, (2) the effectiveness of that intervention for reducing distress when compared with a standard care group, and (3) the costs of providing the treatment as compared to costs of physician time to answer distress-driven questions as part of standard care. Although the per-minute cost of providing the psychological intervention was marginally greater than standard care, providing the intervention was significantly cheaper in terms of distress reduction. Inclusion of 60% payer reimbursement rates for the intervention further suggested that incorporating a psychological intervention into standard medical care for melanoma patients would potentially generate revenue.

Minimal Contact Intervention with Autologous BMT Patients: Impact on QOL and Emotional Distress

Bone marrow transplantation (BMT) is often a last treatment option for individuals who have experienced relapse or treatment failure and is often accompanied by increased levels of distress and reductions in quality of life (QOL). Despite this, few studies have been designed to improve post-BMT QOL and reduce distress. The current study examined the course of distress and QOL in 26 autologus BMT patients and the effect on distress and QOL of providing a minimal contact workbook intervention. Physical well-being decreased following the BMT, but increased at 2- and 6-month follow-up assessments, and distress did not significantly vary over the course of the study for patients in the standard care and workbook intervention groups. Examination of the reasons for the lack of group differences revealed that approximately half of the individuals randomized to the workbook intervention did not look at the material; with those that did reporting higher QOL, decreased anxiety, more adaptive coping, and decreased religiosity. The results argue for the importance of targeting patients at need prior to the transplant procedure, triaging them based on specific characteristics, and providing treatments that match these characteristics.

Comparison of headache parameters using headache type and emotional status

OBJECTIVE The literature on the impact of headache has traditionally focused on the relationship of subject variables to specific headache types. Recently, increasing attention is being paid to the impact on disease of emotional distress. The current study was designed to determine whether differences in subject variables arose when comparing them by headache type vs. empirically derived emotional distress clusters. METHOD A review of responses to measures of headache impact (e.g., duration, medication use) and emotional distress (Brief Symptom Inventory, BSI) completed by 292 patients attending a headache clinic was conducted. Patient responses were analyzed by headache type and emotional distress cluster. RESULTS Comparison by headache type revealed that combined headaches were of longer duration, used more medications, and were more likely to have seen a chiropractor. Comparison by distress cluster revealed high-distress patients to have missed more days of work, have legal involvement, have sought psychological services, and to be male. CONCLUSION The results suggest that clinically useful information can be obtained by using both headache diagnosis and emotional status. In addition, this information may be useful by providing additional knowledge that may lead to different clinical protocols in headache management.

Coping and sensitivity to aversive events

To test further the sensitivity to aversive events hypothesis, males and females varying in level of depressed mood listened to positive, negative, and neutral social scenes while psychophysiological measurements were obtained. In addition, the relations among response styles, coping strategies, and psychological adjustment were examined. Results indicated that only dysphoric females responded in ways consistent with the sensitivity hypothesis, exhibiting greater electrodermal responses to negative social scenes compared to nondysphoric females. No differences in psychophysiological sensitivity were found between dysphoric and nondysphoric males. Dysphoric students engaged in more ruminative type responses in reaction to their depressed mood and reported using more avoidant coping strategies in response to stress. In particular, females utilized more ruminative strategies in response to a depressed mood and more emotion-focused coping strategies in response to stressful events in general. The implications for these results are discussed within a diathesis-stress framework.