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Goals Of Work: Fatigue, pain, and emotional distress are common symptoms among patients with cancer. We sought to learn about patient perceptions of these symptoms and their treatment.Materials and Methods: At a baseline assessment and two monthly follow-up assessments, we asked a diverse sample of patients with solid tumor or lymphoma (N = 99) about their fatigue, pain and distress, their treatment for these symptoms, and their satisfaction with treatment via standardized questionnaires and semistructured interviews.Main Results: In this observational study, patients reported fatigue, pain, emotional distress, and general quality of life at expected levels. Across all assessments, at least half of our sample experienced at least some fatigue, pain, or distress. On the whole, patients and providers do communicate about these concerns, and at least 75% of patients found these discussions helpful when they occurred.Conclusions: Improved symptom identification and communication may optimize the detection of those at risk of morbidity and decreased quality of life because of excess symptom burden. [ABSTRACT FROM AUTHOR]

Purpose: Deleterious germline/somatic homologous recombination repair mutations (HRRm) are present in ∼25% of patients with metastatic castration-resistant prostate cancer (mCRPC). Preclinically, poly(ADP-ribose) polymerase (PARP) inhibition demonstrated synergism with androgen receptor pathway (ARP)-targeted therapy. This trial evaluated the efficacy of ARP inhibitor versus PARP inhibitor versus their combination as first-line therapy in patients with mCRPC with HRRms., Patients and Methods: BRCAAway is a biomarker preselected, randomized, phase 2 trial. Patients with BRCA1/2 and/or ATM alterations were randomized 1:1:1 to Arm1: abiraterone (1,000 mg)/prednisone (5 mg BID) (Abi/pred), Arm2: olaparib (300 mg BID) (Ola), or Arm3: abiraterone/prednisone + olaparib (Abi/pred + Ola). Single-agent arms could cross over at progression. Exploratory Arm4 patients with other HRRms received olaparib alone. The primary endpoint was progression-free survival (PFS), and secondary endpoints were objective response, PSA response, and safety., Results: Sixty-one of 165 eligible patients had BRCA1/2 or ATM mutations: median age: 67 (IQR, 62-73) years. Mutations: BRCA1 n = 3, BRCA2 n = 46, ATM n = 11, and multiple n = 1; 33 germline and 28 somatic mutations. Median PFS [95% confidence interval (CI)]: Abi/pred, 8.6 months (m; 2.9, 17), Ola, 14 m (8.4, 20), and Abi/pred + Ola, 39 m [22, not reached (NR)]. There were no G4/5 adverse events; 8/19 patients on Abi/pred treatment crossed over to Ola, and 8/21 vice versa. Median PFS (95% CI) from crossover: Ola-after-Abi/pred, 8.3 m (5.5, 15) and Abi/pred-after-Ola, 7.2 m (2.8, NR). Median PFS (95% CI) from randomization: Ola-after-Abi/pred, 16 m (7.8, 25) and Abi/pred-after-Ola, 16 m (11, NR). Seventeen of 165 patients with other HRRms received olaparib: median PFS (95% CI): 5.5 m (2, 11)., Conclusions: In patients with mCRPC with BRCA1/2 or ATM HRRm, Abi/pred + Ola was well tolerated and demonstrated longer PFS versus either agent alone or sequentially., (©2024 American Association for Cancer Research.)

Purpose: Patients with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy and a short PSA doubling time are at risk for distant metastases. Apalutamide, an androgen receptor antagonist, and abiraterone acetate plus prednisone (AAP) prolong survival in the metastatic setting. We evaluated whether intensification of androgen-deprivation therapy (ADT) improves outcomes in BRPC., Patients and Methods: PRESTO is a randomized phase III, open-label trial in patients with BRPC and PSA doubling time ≤9 months (ClinicalTrials.gov identifier: NCT03009981). Patients were randomly assigned 1:1:1 to receive a finite 52-week treatment course with ADT control, ADT + apalutamide, or ADT + apalutamide + AAP. The primary end point was PSA progression-free survival (PSA-PFS), defined as serum PSA >0.2 ng/mL after treatment completion., Results: Five hundred three patients were enrolled. The median PSA was 1.8 ng/mL (IQR, 1.0-3.6). At the first planned interim analysis, both experimental arms significantly prolonged PSA-PFS compared with the control arm (median, 24.9 months for ADT + apalutamide v 20.3 months for ADT; hazard ratio [HR], 0.52 [95% CI, 0.35 to 0.77]; P = .00047; median, 26.0 months for ADT + apalutamide + AAP v 20.0 months for ADT; HR, 0.48 [95% CI, 0.32 to 0.71]; P = .00008). Median time to testosterone recovery did not differ across treatment arms. The most common grade ≥3 adverse event was hypertension (7.5%, 7.4%, and 18% in ADT, ADT + apalutamide, and ADT + apalutamide + AAP arms, respectively)., Conclusion: Intensified AR blockade for a finite duration prolongs PSA-PFS with a manageable safety profile, without adversely affecting time to testosterone recovery. The addition of apalutamide to ADT should be considered in patients with high-risk BRPC.

Background: E3805 (CHAARTED) is a phase 3 trial demonstrating improved survival for men with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to treatment with docetaxel (D) and androgen-deprivation therapy (ADT) versus ADT alone. We assessed the association of baseline body mass index (BMI) and metformin exposure with quality of life (QOL) and prostate cancer outcomes including survival in patients enrolled in the CHAARTED study., Methods: We performed a posthoc exploratory analysis of the CHAARTED trial of men with mHSPC randomized to treatment with ADT with or without D between 2006 and 2012. Cox proportional hazards models and Kruskal-Wallis test were used to evaluate the association between BMI with QOL and prostate cancer outcomes and between metformin exposure and survival., Results: In 788 of 790 enrolled patients with prospectively recorded baseline BMI and metformin exposure status, lower BMI was not associated with survival, but was associated with high volume disease (p < 0.0001) and poorer baseline QOL on functional assessment of cancer therapy-prostate (p = 0.008). Only 68 patients had prevalent metformin exposure at baseline in the CHAARTED trial. Four groups were identified: ADT + D + metformin (n = 39); ADT + D (n = 357); ADT + metformin (n = 29); and ADT alone (n = 363). Baseline clinicopathologic characteristics were similar between groups. In this small exploratory multivariable analysis, metformin exposure was not associated with survival (hazard ratio: 1.15; 95% confidence interval: 0.81-1.63, p = 0.44)., Conclusions: There was no link between baseline BMI and survival, but lower baseline BMI was associated with features of greater cancer burden and poorer QOL., (© 2022 Wiley Periodicals LLC.)

Purpose: Although androgen deprivation therapy (ADT) and androgen receptor (AR) signaling inhibitors are effective in metastatic prostate cancer, resistance occurs in most patients. This phase I/II trial assessed the safety, pharmacokinetic impact, and efficacy of the glucocorticoid receptor (GR) antagonist mifepristone in combination with enzalutamide for castration-resistant prostate cancer (CRPC)., Patients and Methods: One hundred and six patients with CRPC were accrued. Phase I subjects were treated with enzalutamide monotherapy at 160 mg per day for 28 days to allow steady-state accumulation. Patients then entered the dose escalation combination portion of the study. In phase II, patients were randomized 1:1 to either receive enzalutamide alone or enzalutamide plus mifepristone. The primary endpoint was PSA progression-free survival (PFS), with radiographic PFS, and PSA response rate (RR) as key secondary endpoints. Circulating tumor cells were collected before randomization for exploratory translational biomarker studies., Results: We determined a 25% dose reduction in enzalutamide, when added to mifepristone, resulted in equivalent drug levels compared with full-dose enzalutamide and was well tolerated. However, the addition of mifepristone to enzalutamide following a 12-week enzalutamide lead-in did not delay time to PSA, radiographic or clinical PFS. The trial was terminated early due to futility., Conclusions: This is the first prospective trial of dual AR-GR antagonism in CRPC. Enzalutamide combined with mifepristone was safe and well tolerated but did not meet its primary endpoint. The development of more specific GR antagonists combined with AR antagonists, potentially studied in an earlier disease state, should be explored., (©2022 American Association for Cancer Research.)

Aim: To validate the total illness burden index for prostate cancer (TIBI-CaP) in castration-resistant prostate cancer (CRPC) patients., Patients & Methods: Baseline comorbidity scores collected using the TIBI-CaP were compared with the baseline patient-reported health-related quality of life using the SF-12v2 and FACT-P questionnaires in 302 patients enrolled in the Treatment Registry for Outcomes in CRPC Patients (TRUMPET)., Results: Baseline TIBI-CaP scores were negatively correlated with all baseline SF-12v2 domain/composite (p < 0.001) and FACT-P subscale/total (p < 0.020) scores. There was a significant decreasing linear trend in SF12v2 and FACT-P scores over the categories based on TIBI-CaP quartiles of comorbidity burden (from 'least' to 'severe')., Conclusion: The TIBI-CaP is a valid measure of comorbidity burden in patients with CRPC in the real world.

Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database ( ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/mL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/mL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/mL compared with > 4 ng/mL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/mL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/mL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/mL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival.

Objective: To conduct a phase II trial of the combination of carboplatin, prednisone, and everolimus in metastatic castrate-resistant prostate cancer (mCRPC) as mTOR inhibition can overcome resistance to chemotherapy in prostate cancer., Methods: Patients with progressive mCRPC pretreated with docetaxel-based regimen were eligible. Performance status of 0-1 and adequate bone marrow, renal, and liver function were required. Primary end point was time to progression. Treatment consisted of carboplatin (starting dose equal to area under the curve (AUC of 5) intravenously every 21 days along with oral everolimus 5 mg once daily and prednisone 5 mg twice daily., Results: Twenty-six patients were enrolled with median age of 69 years with 8 patients of African American origin. Grade 3 or 4 thrombocytopenia or neutropenia in 4 of 6 initial patients required dose adjustment of carboplatin to AUC of 4 for subsequent patients. There were no pharmacokinetic interactions between carboplatin and everolimus. The median time to progression was 2.5 months (90% confidence interval [CI], 1.8-4.3 months), and median overall survival was 12.5 months (90% CI, 7.7-18.7 months). Of 10 patients, 8 that demonstrated positive nuclear phosphorylated AKT (pAKT) staining on immunohistochemistry progressed within 9 weeks, whereas 2 patients with negative staining continued without progression for prolonged durations of 30 and 48 weeks. TSC1 gene mutations did not correlate with clinical outcome., Conclusion: The addition of the mTOR inhibitor everolimus to carboplatin demonstrated minimal clinical efficacy in metastatic prostate cancer. pAKT testing warrants further evaluation as a predictive marker of response to everolimus therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone., Methods: We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone., Results: A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%., Conclusions: Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.).

Purpose: Intermittent androgen deprivation therapy in patients with prostate specific antigen progression after localized prostate cancer treatment is an alternative to standard continuous androgen deprivation therapy. Intermittent androgen deprivation therapy allows for testosterone recovery during off cycles. This stimulates regrowth and differentiation of the regressed prostate tumor, lessens the side effects of continuous androgen deprivation therapy and potentially prolongs survival. Previously intermittent androgen deprivation therapy coupled with finasteride was shown to prolong survival in animals bearing androgen sensitive prostate tumors when the off cycle duration was not prolonged but rather fixed at 10 to 14 days. Regressed prostate tumor xenografts with testosterone replacement were initially responsive to 5α-reductase inhibition but growth resumed after several days. In shorter off cycles of testosterone recovery 5α-reductase inhibition might maximize tumor growth inhibition during intermittent androgen deprivation therapy and perhaps increase survival., Materials and Methods: We used the LNCaP xenograft tumor model to evaluate the effectiveness of short off cycles of 4 days coupled with 5α-reductase inhibition on survival and tumor regrowth while on intermittent androgen deprivation therapy., Results: Dutasteride inhibited initial testosterone induced tumor regrowth off cycles 1 and 2, and significantly increased survival., Conclusions: These results further support the potential for intermittent androgen deprivation therapy combined with 5α-reductase inhibition to improve survival in patients with prostate cancer when off cycle duration is short or very short., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The androgen receptor pathway remains active in men with prostate cancer whose disease has progressed following surgical or medical castration. Orteronel (TAK-700) is an investigational, oral, nonsteroidal, selective, reversible inhibitor of 17,20-lyase, a key enzyme in the production of androgenic hormones., Experimental Design: We conducted a phase I/II study in men with progressive, chemotherapy-naïve, metastatic castration-resistant prostate cancer, and serum testosterone <50 ng/dL. In the phase I part, patients received orteronel 100 to 600 mg twice daily or 400 mg twice a day plus prednisone 5 mg twice a day. In phase II, patients received orteronel 300 mg twice a day, 400 mg twice a day plus prednisone, 600 mg twice a day plus prednisone, or 600 mg once a day without prednisone., Results: In phase I (n = 26), no dose-limiting toxicities were observed and 13 of 20 evaluable patients (65%) achieved ≥50% prostate-specific antigen (PSA) decline from baseline at 12 weeks. In phase II (n = 97), 45 of 84 evaluable patients (54%) achieved a ≥50% decline in PSA and at 12 weeks, substantial mean reductions from baseline in testosterone (-7.5 ng/dL) and dehydroepiandrosterone-sulfate (-45.3 μg/dL) were observed. Unconfirmed partial responses were reported in 10 of 51 evaluable phase II patients (20%). Decreases in circulating tumor cells were documented. Fifty-three percent of phase II patients experienced grade ≥3 adverse events irrespective of causality; most common were fatigue, hypokalemia, hyperglycemia, and diarrhea., Conclusions: 17,20-Lyase inhibition by orteronel was tolerable and results in declines in PSA and testosterone, with evidence of radiographic responses., (©2014 AACR)

Objectives: To examine the concordance between clinicians and men diagnosed with prostate cancer on a clinician-derived pathophysiological classification of the following self-reported urinary complications: storage (irritative), voiding (obstructive), and leakage/incontinence., Materials and Methods: Fourteen urology experts classified 37 urinary function questionnaire items into 3 primary conceptual dimensions (e.g., storage [irritative], voiding [obstructive] and urinary leakage/incontinence) that would best reflect each item's content. In addition, 218 patient participants provided responses to the 37 items. Using classifications by experts to develop the conceptual framework, the structure was tested using confirmatory factor analyses with patient data., Results: Expert consensus was achieved in the classification of 31 out of 37 items. Using the 3-factor conceptual framework and patient data, the fit indices for the overall correlated factor model suggested an acceptable overall model fit. The analyses of the separate domains showed acceptable fit for the storage/irritative domain and the leaking/incontinence domain. The dimensionality of the voiding/obstructive domain was too difficult to estimate., Conclusions: Our analysis found items that conceptually and psychometrically support 2 constructs (leaking/incontinence and storage/irritative). The consistency of this support between the groups suggests a clinical relevance that is useful in treating patients. We have conceptual support for a third hypothesis (voiding/obstructive), although there were too few items to assess this psychometrically. Relative motivating factors of bother and urinary complaints were not addressed and remain an unmet need in this field., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Owing to the spectrum of symptoms, side effects, and concerns in clinically advanced prostate cancer (PC), effective symptom assessment is imperative. In line with recent regulatory guidance on the development of patient-reported outcomes, we undertook a multistep/multistudy approach to develop and test a new symptom index (NCCN FACT-Prostate Symptom Index-17 that can be used to examine the effectiveness of noncurative treatments in advanced PC., Methods: This included significant input from two waves of expert medical providers (n=66 and 11, respectively) and two waves of patient engagement and testing (n=50 and 24, respectively). The resulting 17-item symptom index for advanced PC was then divided into sets or categories based on whether the symptoms are predominantly disease or treatment related., Results: Preliminary reliability estimates suggest good internal consistency (α=0.86) and relationships with expected outside validity criteria are moderate to strong., Conclusions: This new tool may help clinicians and researchers quickly target and measure important symptoms and concerns in advanced PC, leading to increased knowledge of treatment effectiveness of noncurative therapies and improvements in the quality of patient care. Copyright © 2010 John Wiley & Sons, Ltd., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background: Intermittent androgen deprivation therapy (IADT) was developed to improve the quality of life and retard prostate cancer progression to castration resistance. IADT involves regrowth of the tumor during the off cycle upon testosterone recovery. Our previous studies showed that testosterone is more potent than dihydrotestosterone (DHT) in the induction of a subset of androgen-responsive genes during rat prostate regrowth. However, it is not clear if the same phenomenon would occur during androgen-induced regrowth of prostate tumors. Understanding the differences between testosterone and DHT in inducing androgen-responsive genes during prostate tumor regrowth may provide new insight for improving IADT., Methods: Nude mice bearing androgen-sensitive LNCaP xenograft were castrated and followed up for 7-10 days before being randomized into various androgen manipulations, consisting of continuous castration (C) or testosterone replacement (T) in the absence or presence of dutasteride (D), a 5alpha-reductase inhibitor that blocks the conversion of testosterone to DHT. Testes-intact animals in the absence or presence of D were used as controls. The expression of five androgen-responsive genes, including the tumor suppressor U19/Eaf2, was determined using real-time RT-PCR, 3 days after randomization., Results: In LNCaP tumors, the expression of U19/Eaf2 was higher in the T+D group as compared with T alone (2.87-fold, P < 0.05). In contrast, dutasteride treatment in testes-intact animals inhibited the expression of U19/Eaf2., Conclusions: Inhibition of 5alpha-reductase during LNCaP tumor regrowth enhanced the expression of U19/Eaf2, an androgen-regulated tumor suppressor. This finding suggests that off cycle 5alpha-reductase inhibition may enhance the efficacy of IADT., ((c) 2010 Wiley-Liss, Inc.)

Background: We have previously reported that finasteride administration in intermittent androgen deprivation therapy (IADT) can improve survival of nude mice bearing LNCaP xenograft tumors when the duration of off-cycle in IADT was fixed. A recent retrospective study showed that addition of finasteride doubled the duration of the off-cycle, without changing progression to castration resistance. In view of the above difference, we attempted to investigate the relationship of 5alpha-reductase inhibition with the off-cycle interval and overall survival in a murine model., Methods: Subcutaneous LNCaP tumors were established in nude mice (Balb/C-Nu). After the tumors reached a size of 0.5 cm in diameter, the mice were castrated and followed up for 2 weeks after which they were randomized to continuous androgen deprivation (CAD), CAD plus finasteride, IADT, and IADT plus finasteride. The off-cycle was discontinued when the tumor volume was doubled. Subsequent cycles were carried out similarly., Results: Use of finasteride during the off-cycle of IADT doubled the first off-cycle duration. However, prolongation of the off-cycle by finasteride did not translate into an increase in overall survival., Conclusions: The survival advantage of IADT + finasteride over IADT that we previously reported was lost when the off-cycle prolongation by finasteride was allowed. Maximum possible lengthening of the off-cycle by 5alpha-reductase inhibition is not associated with survival improvement in this animal model.

Purpose: Docetaxel is standard of care for androgen-independent prostate cancer (AIPC). Doxercalciferol (1 alpha-hydroxyvitamin D2) had modest activity in phase I/II trials. Preclinical data support combining vitamin D analogues with docetaxel to treat AIPC., Experimental Design: Chemotherapy-naive men with metastatic AIPC were randomized 1:1 to receive, on a 4-week cycle, docetaxel (35 mg/m2 i.v., days 1, 8, and 15) with or without doxercalciferol (10 microg orally, days 1-28). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were progression-free survival, overall survival, objective response, and toxicity. Survival was analyzed as intent to treat., Results: Seventy patients were randomized. Median follow-up was 17.6 months (range, 3.3-45.2). PSA response rate was 46.7% [95% confidence interval (95% CI), 30-64] in the doxercalciferol arm and 39.4% (95% CI, 25-56) with placebo (P = 0.560). Median progression-free survival in the doxercalciferol arm was 6.17 months (95% CI, 4.20-10.7) versus 6.20 months (95% CI, 4.83-9.07) with placebo (P = 0.764). Median overall survival in the doxercalciferol arm was 17.8 months (95% CI, 14.9-23.6) versus 16.4 months (95% CI, 11.9-23.8) with placebo (P = 0.383). Twenty-four patients in the doxercalciferol arm and 23 in the placebo arm were evaluable for objective response. No complete responses were observed. Partial objective response rate was 12.5% with doxercalciferol versus 8.7% with placebo (P = 0.672). Rate of grade > or =3 toxicity was 46% with doxercalciferol versus 42% with placebo (P = 0.785)., Conclusions: Daily doxercalciferol with weekly docetaxel did not enhance PSA response rate or survival. Toxicity was similar between arms. Despite the disappointing results of this study, other vitamin D analogues remain under active investigation.

Fatigue, pain, distress, and anorexia are four commonly encountered symptoms in cancer. To evaluate the usefulness of a single-item screening for these symptoms, 597 ambulatory outpatients with solid tumors were administered a self-report screening instrument within the first 12 weeks of chemotherapy. Patients rated the severity of each symptom on a 0-10 scale, at its worst over the past three days, with higher ratings associated with higher symptom levels. From this sample, 148 patients also completed a more comprehensive assessment of these symptoms. Two criteria were used to determine optimal cut-off scores on the screening items: 1) the sensitivity and specificity of each screening item to predict clinical cases using receiver-operating characteristics analysis and 2) the proportion of patients at each screening score who reported that some relief of the target symptom would significantly improve their life. Optimal cut-off scores ranged from 4 to 6 depending on the target symptom (area under the curve range=0.68-0.88). Use of single-item screening instruments for fatigue, pain, distress, and anorexia may assist routine clinical assessment in ambulatory oncology practice. In turn, such assessments may improve identification of those at risk of morbidity and decreased quality of life due to excess symptom burden.

We expanded an existing 33-item physical function (PF) item bank with a sufficient number of items to enable computerized adaptive testing (CAT). Ten items were written to expand the bank and the new item pool was administered to 295 people with cancer. For this analysis of the new pool, seven poorly performing items were identified for further examination. This resulted in a bank with items that define an essentially unidimensional PF construct, cover a wide range of that construct, reliably measure the PF of persons with cancer, and distinguish differences in self-reported functional performance levels. We also developed a 5-item (static) assessment form ("BriefPF") that can be used in clinical research to express scores on the same metric as the overall bank. The BriefPF was compared to the PF-10 from the Medical Outcomes Study SF-36. Both short forms significantly differentiated persons across functional performance levels. While the entire bank was more precise across the PF continuum than either short form, there were differences in the area of the continuum in which each short form was more precise: the BriefPF was more precise than the PF-10 at the lower functional levels and the PF-10 was more precise than the BriefPF at the higher levels. Future research on this bank will include the development of a CAT version, the PF-CAT.

Objective: Cancer-related fatigue (CRF) is one of the most common unrelieved symptoms experienced by patients. CRF is underrecognized and undertreated due to a lack of clinically sensitive instruments that integrate easily into clinics. Modern computerized adaptive testing (CAT) can overcome these obstacles by enabling precise assessment of fatigue without requiring the administration of a large number of questions. A working item bank is essential for development of a CAT platform. The present report describes the building of an operational item bank for use in clinical settings with the ultimate goal of improving CRF identification and treatment., Study Design and Setting: The sample included 301 cancer patients. Psychometric properties of items were examined by using Rasch analysis, an Item Response Theory (IRT) model., Results and Conclusion: The final bank includes 72 items. These 72 unidimensional items explained 57.5% of the variance, based on factor analysis results. Excellent internal consistency (alpha=0.99) and acceptable item-total correlation were found (range: 0.51-0.85). The 72 items covered a reasonable range of the fatigue continuum. No significant ceiling effects, floor effects, or gaps were found. A sample short form was created for demonstration purposes. The resulting bank is amenable to the development of a CAT platform.

Background: The objective of this study was to construct and validate a brief, clinically-relevant symptom index for advanced prostate cancer., Methods: Questions were extracted from a commonly-used multi-dimensional cancer quality of life instrument with prostate-specific items, the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Surveys of disease-related symptoms were presented to an international sample of 44 expert physicians. Each expert narrowed the list to no more than five of the most important symptoms or concerns to monitor when assessing the value of treatment for advanced prostate cancer. Symptoms/concerns endorsed at a frequency greater than chance probability (17%) were retained for the symptom index and called the FACT Advanced Prostate Symptom Index-8 (FAPSI-8): pain (three items), fatigue, weight loss, urinary difficulties (two items), and concern about the condition becoming worse. The FAPSI-8 was validated using data from a clinical trial of 288 men being treated for hormone refractory prostate cancer., Results: The FAPSI-8 showed good internal consistency (r = 0.67-0.80); association with existing FACT scales (e.g., FACT-P, Physical Well-being, Functional Well-being; r = 0.44-0.85, p <.0001), responsiveness to clinical change (Guyatt's Responsiveness statistic = 1.29), and ability to differentiate patients by performance status (p <.0001). A six-item alternate version of the FAPSI was also evaluated with comparable results., Conclusions: This project produced a reliable and valid list of the eight most important clinician-rated targets of drug therapy for advanced prostate cancer. These questions perform comparably to the longer derivative questionnaire. Examination of patient agreement with this priority list and the extent to which changes in these 8 targets are related to meaningful clinical benefit to the patient are important next steps for future research.

Advanced non-small-cell lung cancer (NSCLC) remains an incurable disease despite significant progress in chemotherapy. We conducted a phase II clinical trial to investigate the efficacy and toxicity of a cisplatin, etoposide, and 5-fluorouracil (5-FU) combination in advanced metastatic and/or recurrent NSCLC. Forty patients with advanced, recurrent, or metastatic, measurable NSCLC were treated with cisplatin, 60 mg/m2 intravenously (i.v.) on day 1; etoposide, 120 mg/m2/day i.v. on days 1, 2, and 3; and 5-FU. 1,000 mg/m2/day i.v. continuous infusion on days 1 through 5. Treatment was administered in 4-week cycles. Thirty patients had distant metastases and were previously untreated, and 10 patients had recurrent disease after prior treatment with either surgery (1 patient), radiation therapy (5 patients), or both treatments (4 patients). Twenty-nine patients were evaluable for response. Seven (24%) patients achieved a partial remission (PR), 18 (62%) had stable disease (SD), and 8 (14%) had progressive disease (PD). Overall median survival was 7.9 months (range, 0.4-27.4 months). Patients who achieved a PR had a median survival of 23.5 months (9.3-27.4 months). In contrast, patients with SD had a median survival of 9.9 months (2.5-25.3 months), and patients with PD had a median survival of 2.1 months (1-9.3 months). Median duration of response of 27.1 weeks (4.9-76.5 weeks) for patients with PR, and time to progression was 13.4 weeks (3.7-54.5 weeks) for patients with SD. Toxicity was primarily hematologic and gastrointestinal, and there were three deaths due to infection. The combination of cisplatin, 5-FU, and etoposide as administered in this study appears to have considerable toxicity and does not appear to be superior to other cisplatin-containing regimens used for the treatment of advanced NSCLC.