Sloan, Jeffrey A.

Abstract Background: Several randomized trials had shown the benefits of palliative care interventions in patients with metastatic cancer. However, there is a paucity of data evaluating the benefit of palliative care in racially diverse patient populations, and no systematic analysis of the effect of race/ethnicity on these interventions have been done. Recently, our group completed a randomized clinical trial showing that an Advanced Registered Nurse Practitioner (ARNP)-directed palliative care intervention for patients with metastatic cancer leads to improvement in the patients' emotional quality of life (EQoL) as determined by a validated quality of life tool, the FACT-G (PAL-1 study, Dyar et al: J Palliative Medicine 15: 890, 2012). The PAL-2 pilot study reported herein evaluated the feasibility of this program in underserved racially diverse patient populations. PAL-2 incorporated PAL-1 interventions of advanced directives discussions, hospice services education and assessment of QoL using the FACT-G tool. In addition, the PAL-2 program incorporated home visits and implementation of FACT-G driven palliative interventions. Aims: The primary endpoint was to assess the feasibility of an ARNP-directed palliative care intervention trial for racially diverse cancer patients. The ultimate goal was to use the data from this pilot study to plan for a subsequent larger randomized trial. Secondary end points included evaluation of the effects of the intervention on the patient's QoL and emotional well-being as determined by a change in FACT-G , EQoL scores, as well as measurement of knowledge about hospice as determined by changes in a hospice knowledge questionnaire (HKQ) scores. Methods: 25 adult patients with metastatic cancer were recruited. All patients completed a FACT-G and a HKQ at baseline, had an ARNP consultation, and a home visit whenever feasible, with a second ARNP consultation visit 4 weeks later. Results: Of 25 patients who participated (16 males, 9 females, mean age 57, age range 33-89, 16 Caucasians (C), 8 African Americans (AA), 1 Asian), 15 patients (8C, 7AA) completed their first and second ARNP consultation visits and 12 (5C, 7AA) completed all questionnaires and were available for secondary endpoint analysis. The main reason for failure to complete the study was disease progression. The most common interventions implemented were advanced directives discussions, assessment of family support, stress management education, assessment of psychological status, spirituality assessment, financial assistance programs, and pain and symptom management. Interventions offered but not selected by most patients included: use of computer based social networking tools, psychological interventions, occupational training and cancer support group participation. Home visits were completed in 11 patients and provided significant insight into the patients' needs and their available support. The palliative care intervention and the FACT-G tool were well accepted by patients. There was no significant change in the EQoL as a result of the intervention ( EQoL change, mean (SD)= -1.2 (13.52), median 3.7, p=0.6719). A trend was observed towards improvement in HKQ results (n=8, change from baseline score mean (SD)= 21.2 (29.58), median 15.4, p= 0.0938). Conclusions: The FACT-G tool was well received by the patients and providers, and its use can be incorporated into clinical care to direct palliative care interventions and assess their impact on patients' QoL. A nurse practitioner-directed palliative care intervention is well accepted by patients of diverse race. Significant attrition of participants due to disease progression (40%) will need to be considered in planning larger randomized trials. Randomized clinical trials evaluating the impact of race, ethnicity and socio-economic status on the benefits of different palliative care interventions in patients with metastatic cancer are feasible and needed. Citation Format: Gerardo Colon-Otero, Mary Lesperance, Fauzia Rana, Robert Shannon, Jeffrey Sloan. A nurse practitioner-directed palliative care intervention trial in racially diverse patients with metastatic cancer. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A42.

Dieser zweiteilige Artikel stützt sich auf ein vergleichendes und beschreibendes Modell, anhand dessen sich die Wahrnehmungen der Symptombelastung von Lungenkrebspatientinnen und -patienten und die Einschätzungen der sie hauptsächlich pflegenden Angehörigen im familiären Rahmen untersuchen lassen. Der zweite Teil beschreibt die Resultate der qualitativen Komponente dieser Untersuchung. Eine Auswahl von 37 Paaren, die aus Patient/in und pflegendem Familienmitglied bestanden, füllte die McCorkle and Young Symptom Distress Scale (SDS) aus. Die Gesamtresultate der pflegenden Angehörigen korrelierten mäßig1 mit jenen der Patienten (r = 0.71; P < 0.001). Bei 10 der 13 Symptome fanden sich keine bedeutsamen Unterschiede in der Einstufung. Pflegende sollten sich daher bewußt sein, daß die pflegenden Angehörigen die Symptombelastung von Lungenkrebspatienten bei mindestens 10 der 13 auf der SDS aufgeführten Symptome zuverlässig einschätzen. Dies ist vor allem dann von großer Bedeutung, wenn der Patient oder die Patientin selbst nicht in der Lage ist, über seine/ihre Symptombelastung zu sprechen.

Abstract Purpose: Flavopiridol, a cyclin-dependent kinase inhibitor, transcription inhibitor, and DNA-interacting agent, was combined with cisplatin or carboplatin to establish toxicities, evaluate pharmacokinetics, and examine its effects on patient cancers and levels of selected polypeptides in patient peripheral blood mononuclear cells (PBMC). Experimental Design: Therapy was given every 3 weeks. Stage I: cisplatin was fixed at 30 mg/m2 with escalating flavopiridol. Stage II: flavopiridol was fixed at the stage I maximum tolerated dose (MTD) with escalation of cisplatin. Stage III: flavopiridol was fixed at the stage I MTD with escalation of carboplatin. Results: Thirty-nine patients were treated with 136 cycles of chemotherapy. Neutropenia was seen in only 11% of patients. Grade 3 flavopiridol/CDDP toxicities were nausea (30%), vomiting (19%), diarrhea (15%), dehydration (15%), and neutropenia (10%). Flavopiridol combined with carboplatin resulted in unexpectedly high toxicities and one treatment-related death. Stable disease (&gt;3 months) was seen in 34% of treated patients, but there were no objective responses. The stage II MTD was 60 mg/m2 cisplatin and 100 mg/m2/24 hours flavopiridol. As given, CDDP did not alter flavopiridol pharmacokinetics. Flavopiridol induced increased p53 and pSTAT3 levels in patient PBMCs but had no effects on cyclin D1, phosphoRNA polymerase II, or Mcl-1. Conclusions: Flavopiridol and cisplatin can be safely combined in the treatment of cancer patients. Unexpected toxicity in flavopiridol/carboplatin-treated patients attenuates enthusiasm for this alternative combination. Analysis of polypeptide levels in patient PBMCs suggests that flavopiridol may be affecting some, but not all, of its known in vitro molecular targets in vivo.

Abstract Objective: Predictors of quality of life (QOL) in patients with metastatic colorectal cancer are lacking. The insulin-like growth factor (IGF) family of proteins is associated with QOL in noncancer populations. We sought to study whether these proteins are associated with QOL in patients with colorectal cancer. Method: We used a cohort of 526 patients with metastatic colorectal cancer treated with combination chemotherapy. Plasma samples of IGF-I, IGF-II, IGF binding protein-3, and C-peptide were collected before initiation of chemotherapy. QOL was measured by the uniscale instrument and the Symptom Distress Scale at baseline and throughout treatment. Results: Baseline plasma levels of IGF-I and IGF-II before initiation of chemotherapy were significantly associated with several important baseline QOL measures in patients with metastatic colorectal cancer. Patients with lower levels of IGF-I reported increased distress with regard to appearance, appetite, cough, and nausea intensity after adjustment for potential confounders. Similarly, decreased levels of IGF-II were predictive of worse quality related to appearance, appetite, fatigue, nausea frequency and intensity, pain frequency, and composite Symptom Distress Scale score. IGF binding protein-3 and C-peptide were not predictive of baseline QOL. Baseline biomarkers were not associated with subsequent changes in QOL during treatment. Higher body mass index was significantly associated with superior baseline QOL in several areas; nonetheless, the association of IGF-I and IGF-II with baseline QOL measures remained significant even after controlling for baseline body mass index. Conclusion: Baseline plasma IGF-I and IGF-II are significantly associated with symptom distress. Whether this association is simply reflective of patient nutritional status and/or disease burden or represents an independent biological effect of IGFs on QOL remains uncertain. Nonetheless, these data suggest that molecular biomarkers may be useful predictors of QOL in cancer patients.

Purpose: We sought to determine the maximum-tolerated dose (MTD) and evaluate the toxicities and clinical activity of two irinotecan (CPT-11), fluorouracil (FU), leucovorin (LV), and oxaliplatin schedules in patients with advanced solid tumors. Additionally, we investigated the effect of CPT-11 on oxaliplatin pharmacokinetics. Patients and Methods: Thirteen patients (cohort 1) received intravenous CPT-11 (infusion) and FU/LV (bolus) on days 1, 8, 15, and 22 and oxaliplatin (infusion) on days 1 and 15 every 6 weeks for a total 37 courses (median, three courses) at three dose levels. Twenty-two cohort 2 patients received intravenous CPT-11/oxaliplatin (infusion, day 1) and FU/LV (90-minute bolus infusion, days 2 to 5) every 3 weeks for a total of 122 courses (median, four courses) at three dose levels. Pharmacokinetic and neurotoxicity assessments were performed at the cohort 2 MTD. Results: Dose-limiting toxicity (DLT) seen in both cohorts at the starting dose required dose de-escalation. Cohort 1 DLT included diarrhea and neutropenia. In cohort 2, diarrhea, vomiting, dehydration, neutropenia, febrile neutropenia, and paresthesias were DLTs. Antitumor activity was seen in both cohorts. In cohort 2, the total platinum area under the curve of patients increased 17% in cycle 2 (P = .048), but objective neurotoxicity was not seen. Conclusion: The toxicities resulting from the addition of oxaliplatin to CPT-11/FU/LV are significant but manageable. The MTDs for the weekly schedule are CPT-11 (75 mg/m2), oxaliplatin (50 mg/m2), FU (320 mg/m2), and LV (20 mg/m2); and, for the 3-weekly schedule, the MTDs are CPT-11 (175 mg/m2), oxaliplatin (85 mg/m2), FU (240 mg/m2), and LV (20 mg/m2). Second-cycle platinum accumulation raises the possibility for enhanced cumulative neurotoxicity with CPT-11/oxaliplatin combinations.