J. Cogswell

Prediction of Survival for Advanced Cancer Patients by Recursive Partitioning Analysis: Role of Karnofsky Performance Status, Quality of Life, and Symptom Distress

We performed an exploratory recursive partitioning analysis (RPA) in 429 metastatic cancer patients who had completed a Functional Assessment of Cancer Therapy–General (FACT-G) and a Memorial Symptom Assessment Scale–Short Form (MSAS-SF) to define survival prognostic groups. The Cox model analysis also was performed. Both RPA and Cox models included Karnofsky performance status (KPS), age, FACT-G subscales, and MSAS-SF subscales as survival predictors. Of 429 patients, 348 patients (81.1%) had expired at time of analysis. The median age was 67 years (27–89), with median length of survival of 147 days. The RPA identified four distinct survival groups (p < .0001) with three variables: KPS, physical well-being, and physical symptom distress. The most significant split was KPS of 50%, followed by physical well-being score of 25 and physical symptom distress score of 0.6. The median survival time was 29 days for patients with KPS < 50%; 146 days for patients with KPS ≥ 50% and physical well-being < 25; 292 days for patients with KPS > 50%, physical well-being ≥ 25, and physical symptom distress score > 0.6; and 610 days for patients with KPS ≥ 50%, physical well-being ≥ 25, and physical symptom distress score ≤ 0.6. The Cox model found, in addition to KPS (p < .0001) and physical well-being (p = .08), different predictors: psychological symptom distress (p = .0007), global distress index (p = .02), and age (p < .0001). We concluded that the KPS, quality of life, and symptom distress scores can be combined to define prognostic groups. Such models may be helpful for clinical decision making.

Phase I Study of Flavopiridol in Combination with Paclitaxel and Carboplatin in Patients with Non-Small-Cell Lung Cancer

PURPOSE The aim of this study was to evaluate the safety and tolerability of escalating doses of flavopiridol/ paclitaxel/carboplatin in patients with advanced-stage non-small-cell lung cancer (NSCLC) as well as the pharmacokinetics and activity of flavopiridol when used in combination with paclitaxel/carboplatin. PATIENTS AND METHODS Eligible patients aged 18-75 years with previously untreated stage IIIB/IV NSCLC received paclitaxel 175 mg/m2 over 3 hours followed by carboplatin area under the curve (AUC) 5 over 1 hour and flavopiridol 30-85 mg/m2 over 24 hours every 3 weeks for 3 cycles. RESULTS Eighteen patients were enrolled at 4 sites in the United States and received flavopiridol 30 mg/m2 (n = 3), 50 mg/m2 (n = 6), 70 mg/m2 (n = 3), or 85 mg/m2 (n = 6). No dose-limiting toxicities (DLTs) occurred at the 50-mg/m2 or 70-mg/m2 dose levels. Two patients treated at the 85-mg/m2 dose level experienced cardiovascular events that did not meet the criteria for DLT but were fatal in 1 case, prompting no further flavopiridol dose escalations and establishment of 70 mg/m2 as the maximum tolerated dose. The most frequently reported adverse events across all dose levels combined were nausea (89%), asthenia (67%), and diarrhea (56%). Flavopiridol concentrations increased rapidly, reached a plateau, and showed a multiphasic decline after the 24-hour infusion. Of 12 patients evaluable for efficacy, 8 achieved a partial response, and 4 had stable disease. CONCLUSION Flavopiridol in doses <or= 70 mg/m2 in a 24-hour infusion can safely be combined with a 3-hour infusion of paclitaxel 175 mg/m2 and a 1-hour infusion of carboplatin AUC 5.

Study of Hormone Refractory Prostate Cancer: Hospital Care and Palliative Care Resource Use at a VA Medical Center

Palliative care plays a central role in the management of hormone refractory prostate cancer patients (HRPC), yet little is known about palliative care resource use. Computerized medical records of a retrospective cohort of 89 consecutive HRPC patients seen at a VA medical center from 1994 to 1999 were reviewed for hospital and palliative care resource use in the last 6 months of life. There were 51 Caucasian and 38 African American patients; 95% of patients were admitted to the hospital for symptom management (median of 2 admissions); 98% visited clinics (median 19 visits); 35% went to the emergency room (median of 1 visit); 60% died in the hospital (median length of last hospitalization of 22 days); 49% received palliative radiation; 52% used rehabilitation; 57% received blood transfusion (median 2 units). Thirty-five patients (40%) received hospice care (median stay 35 days). The most frequently prescribed medications included opioids (90%), laxatives (89%), H2-blockers (57%), antiemetics (55%), diuretics (49%), and corticosteroids (43%). The prevalence of patients receiving opioids, as well as the dose of opioids increased over time. There was no difference in categories of palliative care resource use or survival by race. The median survival for all patients was 13 months. The results begin to highlight the extent of care and resources needed by patients with end-stage HRPC. This information will be of importance in planning palliative care for patients with HRPC and in designing future prospective studies.

Survival of patients who had salvage castration after failure on bicalutamide monotherapy for stage (D2) prostate cancer

Abstract Patients with hormone-naive stage D2 prostate cancer often benefit from castration, This treatment, however, frequently produces many unacceptable physical and psychological side effects, especially in younger and sexually active patients. Bicalutamide is an oral antiandrogen with excellent tolerance and preservation of sexual function. Three institutions participated in phase II and III trials of bicalutamide monotherapy (50 mg daily) as primary therapy in hormone-naive patients with stage D2 prostate cancer. Upon bicalutamide failure, all patients underwent castreation and were followed until death. Fifty-four patients received bicalutamide 50 mg orally once a day. One patient (2%) had complete response, 9 patients (17%) had partial response, and 27 patients (50%) had stable disease. Seventeen patients (31%) had progressive disease. The median time to bicalutamide failure was 47.4 weeks, 70.5 weeks for the responders vs. 25.4 weeks for the nonresponders (p < 0.001). The median survival time after the sequential use of bicalutamide and castration was 119.2 weeks for all 54 patients, 162.0 weeks for the responders, and 73.5 weeks for nonresponders (p < 0.0001). The median survival time after initiation of castration was 71.1 weeks for all 54 patients, 91.4 weeks for bicalutainide responders, and 42.1 weeks for nonresponders (p < 0.01). In hormone-naive patients with stage D? prostate cancer, sequential treatment with bicalutamide monotherapy followed by castration upon failure may produce survival time within the range reported for initial treatment with castration. Thus, considering the favorable quality of life profile of bicalutamide, further studies are needed to define the role of sequential hormonal therapy in younger sexually active patients.

Processes as predictors of outcomes of EOL care at a VA medical center

20646 Background: The objective of the study is to find quality indicators that predict outcomes of EOL care. Methods: Items from performance measures proposed by Earle et al (Int J Qual Health Care 2005;17:505) were used to develop multivariate logistic regression models for the outcomes 1) whether a patient enters into Hospice, 2) dies in an acute care institution, and 3) is admitted into the ICU within one month of death. We analyzed data from a cohort of veteran patients. Process variables included the type of underlying disease, whether pain or symptom medications were administered, whether psychological support was given, and whether patients were admitted to the MICU. Analyses were done with SAS. Conclusions: Supportive care measures, such as pain and symptom medications are associated with increased likelihood of entering Hospice, and support counseling increases the likelihood of dying in an acute care institution and being admitted to the ICU within the last month of life. These findings should ...

A phase II study of erythropoietin (EPO) with low dose dexamethasone (Dexa) for cancer related (CR) fatigue (F)

8046 Background: Fatigue remains the most difficult symptom to treat in pts with advanced cancer. EPO and Dexa are active agents in palliating F, and may have synergistic effects on erythropoesis i...

Phase II trial of docetaxel (D) and high-dose celecoxib (C) in patients (Pts) with hormone resistant prostate cancer (HRPC)

4616 Background: COX-2 is an inducible enzyme, which converts arachidonic acid to prostaglandins. COX-2 is over expressed in 89.3% of our pts with prostate cancer and is an independent predictor of survival (Cogswell et al; Proc ASCO 2003, #1675). Both D and C are angiogenesis inhibitors and induce apoptosis; their combination could be synergistic. In an ongoing pilot trial we determined the effects on PSA, Overall Response(OR), toxicity, and survival. METHODS Eighteen (18) pts with HRPC progressing by rising PSA and radiographic manifestations were treated with D 30mg/m2 IV over 30min,weekly for 3 wks and C 400mg po bid daily of each 4wk cycle. All pts were assessed by PSA and radiological tests every 2 cycles. Dose modifications for hematologic, hepatic and renal toxicity were made. Detailed renal function tests were assessed by a nephrologist. The RECIST criteria and PSA decline by ≥50% were used. Sample size was determined by Simons Optimal Two-Stage design. RESULTS The median age was 73.5 years(55-94), ECOG PS 1(0-1),LDH 180.5 U/L(125-899 ), Hgb 11.9g/dL (8.6-14.6), PSA 215.8 ng/dL (28.5-2675). The median number of cycles was 3(2-6).The median follow up was 6 mos (2-11+). Soft tissue metastases were present in 15 pts (83.3%) and bone metastases in 17 pts (94.4 %). Seventeen(17)pts are evaluable for response. Of these, 11 pts(64.7%) had PSA responses and the PSA normalized in 4pts (23.5%).Soft tissue responses were seen in 5(2CRs + 3PRs)pts(29.4%)and SD in 5pts(29.4%). One pt(5.9%) had an impressive bone scan response. The OR for 11pts was 64.7%. One pt withdrew due to abdominal pain, 2pts(11.7%) had grade III diarrhea and one had grade III nail changes. There was excellent renal tolerance (Yudd et al; Proc ASCO 2004 subm ). CONCLUSIONS The combination of D and C is well tolerated. The OR rate was 64.7%. PSA decline by≥50%, PSA normalization, soft tissue, and bone scan responses were demonstrated. Further accrual and longer follow up will determine its full impact in pts with HRPC. (Supported by Aventis and Pfizer). [Table: see text].