Peter Koo

Randomized Clinical Trial of the Effectiveness of a Self-Care Intervention to Improve Cancer Pain Management

PURPOSE This randomized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with standard care in decreasing pain intensity scores, increasing appropriate analgesic prescriptions, and increasing analgesic intake in oncology outpatients with pain from bone metastasis. PATIENTS AND METHODS Patients were randomly assigned to the PRO-SELF intervention (n = 93) or standard care (n = 81). Patients in the standard care arm were seen by a research nurse three times and were called three times by phone between the home visits. PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention, were taught how to use a pillbox, and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions. Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management. RESULTS Pain intensity scores decreased significantly from baseline (all P <.0001) in the PRO-SELF group (ie, least pain, 28.4%; average pain, 32.5%; and worst pain, 27.0%) compared with the standard care group (ie, least increased by 14.6%, average increased by 1.9%, and worst decreased by 1.2%). The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3% to 37.0% (P =.008) compared with a change from 29.6% to 32.5% in the standard care group. CONCLUSION The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain.

Putting cancer pain management regimens into practice at home

The purpose of this study was to describe the difficulties with pain management that patients and family caregivers bring to a nurses attention during a teaching and coaching intervention. Data were obtained from audiotaped and transcribed interactions between intervention nurses and patients (n = 52) and their family caregivers (n = 33) who were participating in a randomized clinical trial of a nursing intervention called the PRO-SELF Copyright Pain Control Program. Using qualitative content analysis, we found that patients had difficulty in seven areas when they attempted to put a pain management regimen into practice, namely: obtaining the prescribed medication(s), accessing information, tailoring prescribed regimens to meet individual needs, managing side effects, cognitively processing information, managing new or unusual pain, and managing multiple symptoms simultaneously. The findings from this study suggest that the provision of information about cancer pain management to patients and their family caregivers is not sufficient to improve pain control in the home care setting. Patients and their family caregivers require ongoing assistance with problem-solving to optimize their pain management regimen.

The Use of a Responder Analysis to Identify Differences in Patient Outcomes Following a Self-Care Intervention to Improve Cancer Pain Management

Abstract Previously, we demonstrated, in a randomized clinical trial, the effectiveness of a psychoeducational intervention to decrease pain intensity scores and increase patients’ knowledge of cancer pain management with a sample of oncology patients with pain from bone metastasis. In the present study, we evaluated for changes in mood states (measured using the Profile of Mood States), quality of life (QOL; measured using the Medical Outcomes Study Short Form‐36 (SF‐36)), and pain’s level of interference with function (measured using the Brief Pain Inventory (BPI)) from baseline to the end of the intervention first between the intervention and the standard care groups and then within the intervention group based on the patients’ level of response to the intervention (i.e., patients were classified as non‐responders, partial responders, or responders). No differences were found in any of these outcome measures between patients in the standard care and intervention groups. However, when patients in the intervention group were categorized using a responder analysis approach, significant differences in the various outcome measures were found among the three respondent groups. Differences in the physical and mental component summary scores on the SF‐36 and the interference items on the BPI, among the three respondent groups, were not only statistically significant but also clinically significant. The use of responder analysis in analgesic trials may help to identify unique subgroups of patients and lead to the development of more effective psychoeducational interventions.

Pain management autobiographies and reluctance to use opioids for cancer pain management.

Although pain management education results in improved pain control for some patients, it does not work for all patients because some patients remain reluctant or unwilling to use prescribed analgesics to their optimal effect. In a randomized clinical trial that tested the effectiveness of the PRO-SELF© Pain Control Program, 11 patients declined to increase their analgesic use despite moderate to severe pain. These patients were selected for a qualitative analysis of their audiotaped discussions about pain management with their intervention nurses. This analysis revealed that these patients often spontaneously provided detailed explanations about why they were reluctant or unwilling to take analgesics in general or opioids in particular. We termed these explanatory accounts pain management autobiographies because of their narrative character and multilayered, richly detailed quality. Pain management autobiographies included stories about (1) previous experience with chronic pain management, including stigmatizing interactions with clinicians and family members; (2) bad experiences with cancer pain management, including severe constipation; and 3) strongly held conventions about medication use, including the belief that all medications are “toxins” that should be avoided. The study findings suggest that a small subset of patients with cancer pain may need interventions such as individual or family counseling or alternative pain management strategies to augment education about opioids.

Evaluation of novel orthotopic nude mouse models for human small-cell lung cancer

Introduction: Although subcutaneous xenograft models have been widely used to evaluate the antitumor activity of new compounds, these models present a major disadvantage because the tumors do not accurately represent the cancer biology, especially with regard to metastasis and drug sensitivity. Effective murine models of small-cell lung cancer (SCLC) are needed. Methods: To provide strategies for studying new therapies and tumor biology, we developed three orthotopic models of human SCLC (H69A, a variant of the National Cancer Institute [NCI]-H69 cell line selected for invasiveness in vitro, NCI-H187, and NCI-N417) in nude mice. Tumor cells were injected into their lungs and new cell lines were established from these tumors (H69ALu, H187Lu, and N417Lu) to select for a reproducible tumor growth pattern and minimize variations in tumor size. Results: In all three models tumors started as a solitary mass in the left lung and spread to mediastinal and axillary lymph nodes and to the right lung in a pattern similar to that observed in human SCLC. To test the accuracy of this model in representing SCLC as seen in the clinic, we compared the efficacy of chemotherapeutic agents in each model. Irinotecan significantly inhibited the growth and progression of all three human SCLC tumors, and cisplatin, paclitaxel, and etoposide significantly inhibited the growth and progression of H69ALu tumors over the control agent. Conclusions: We have established three orthotopic murine models of human SCLC closely resembling the course of human SCLC seen in the clinic including metastasis to lymph nodes and distant organs. They provide a means for better understanding the biology of this disease and will enable evaluation of novel therapeutic strategies.

Targeting Vascular Endothelial Growth Factor in Patients With Squamous Cell Lung Cancer

Vascular endothelial growth factors (VEGFs) and their receptors are primary regulators of physiologic and pathologic angiogenesis and lymphangiogenesis. There are five members of the VEGF family, including VEGF-A (or VEGF), VEGF-B, VEGF-C, VEGF-D, and placental growth factor, and three structurally related receptors: VEGFR-1, VEGFR-2, and VEGFR-3. VEGF produced from tumor cells induces activation of VEGF/VEGFR signaling axis, triggering several signaling pathways in endothelial cells and cancer cells, which leads to neovascularization and tumor development. Targeting antiangiogenesis has become a key therapeutic strategy for cancer treatment. Angiogenesis is regulated mainly by the binding of VEGF to VEGFR-2, which causes autophosphorylation in several tyrosine residues at the kinase domain and C-terminal tail, with activation of downstream pathways leading to endothelial cell proliferation, survival, migration, and permeability (Fig 1). The major VEGFR-2 phosphorylation sites are Tyr and Tyr, with the former creating a binding site for phospholipase C , SH-2 domain-containing adaptor protein B, and SHC-related adaptor protein, whereas the latter is involved in the activation of guanosine triphosphate binding protein cell division cycle 42 and p38 mitogen-activated protein kinase (MAPK). Phospholipase C activates the MAPK pathway through protein kinase C and Raf, leading to cell proliferation. Binding of SH-2 domain-containing adaptor protein B to VEGFR-2 Tyr causes VEGF-dependent phosphatidylinositol 3 -kinase activation, which increases endothelial cell survival through inhibition of proapoptotic B-cell lymphoma protein 2–associated death promoter and caspase 9 by its downstream effector Akt and increases expression of the antiapoptotic