Trial Outcome Index Research Articles

Impact of Deep Breathing and Relaxation Exercises on Health Related Quality of Life in Breast Cancer Patients Receiving Chemotherapy.

Abstract Background: Though chemotherapy improves outcomes in many cancer patients, it has a profound impact on quality of life (QOL). Alternative medicine is set to assume an increasingly important role in the management of treatment related side effects in cancer patients. Modification of breathing pattern is an essential part of Yoga, which has been shown to improve QOL in cancer patients. Yoga needs a dedicated trainer and requires considerable time commitment. This study examines the impact of self administered breathing and relaxation exercises on patients receiving chemotherapy for breast cancer.Methods: Non metastatic breast cancer patients currently receiving chemotherapy were considered. Patients who received less than 2 cycles of chemotherapy, had hemoglobin less than 9 g/dl, psychiatric illness or poor performance status (ECOG more than 1) were excluded. The breathing and relaxation exercise was a 5 minute long process designed to be performed twice a day at home. Participants were given technique demonstrations and written instructions. A questionnaire was used to assess compliance. FACT-B (version 4) questionnaires were used to obtain objective assessment of Health Related Quality of Life (HRQL) at enrollment and after 3 weeks of exercise. Pre and post intervention scores were analyzed. Out of 15 enrolled patients, 4 had to be excluded due to one of the above reasons.Results: The participants were all women (mean age 58.6) with a diagnosis of non metastatic breast cancer within 12 months. Patient responses were used to calculate scores in the following subscales: Physical Well Being (PWB), Social Well Being (SWB), Emotional Well Being (EWB), Functional Well Being (FWB) and Breast Cancer Subscale (BCS). The subscale scores were used to calculate 3 total scores: Trial Outcome Index (TOI, sum of PWB+FWB+BCS), FACT-G (PWB+SWB+EWB+FWB) and FACT-B (FACT-G + BCS).Baseline CharacteristicsMean Age58.6 RaceHispanic5 (45.4%) African American3 (27.2%) Caucasian1 (9%) other2 (18.1%)EducationSchool3 (27.2%) High School4 (36.3%) College5 (45.4%)Social Support∗24 (36.3%) 37 (63.6%)Stage13 (27.2%) 24 (36.3%) 35 (45.4%)Social Support: score of 1 each for spouse, children or parents and close friends.∗Comparison of pre and post intervention mean scores showed trends towards improvement in four out of five sub scores and all three total scores, although only FACT-B (p=0.04), BCS (p=0.05) and SWB (p=0.05) showed statistically significant increases. Patients with good social support had higher overall scores. Patients who finished education in high school had better scores than patients who had dropped out of school or had gone to college.ResultsSCORE TYPEMEAN (PRE)MEAN (POST)p VALUEFACT-B98.5102.90.04FACT-G7980.80.38TOI∗53.560.90.2PWB∗16.7180.4SWB∗2428.10.05EWB∗17.716.41.0FWB∗2021.20.46BCS∗19.521.50.05TOI: Trial Outcome Index; PWB: Physical Well Being; SWB: Social Well Being; EWB: Emotional Well Being; FWB: Functional Well Being; BCS: Breast Cancer Subscale∗Conclusions: Simple, self administered breathing and relaxation exercises can play an important role in improving QOL in breast cancer patients receiving chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3101.

A randomised, controlled trial of the psychological effects of reflexology in early breast cancer

PurposeTo conduct a pragmatic randomised controlled trial (RCT) to evaluate the effects of reflexology on quality of life (QofL) in women with early breast cancer. Patients and methodsOne hundred and eighty-three women were randomised 6 weeks post-breast surgery to self-initiated support (SIS) (comparator intervention), SIS plus reflexology, or SIS plus scalp massage (control for physical and social contact). Reflexology and massage comprised eight sessions at weekly intervals. The primary end-point was 18 weeks post surgery; the primary outcome measure was the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy (FACT-B) – breast cancer version. The secondary end-point was 24 weeks post surgery. Secondary outcome measures were the Hospital Anxiety and Depression Scale (HADS) and the Mood Rating Scale (MRS). ResultsAt primary end-point, massage, but not reflexology, was significantly better than SIS on the TOI. Reflexology and massage were both better than SIS for MRS relaxation. Massage was better than reflexology and SIS for MRS easygoingness. At secondary end-point, reflexology, but not massage, was better than SIS on the TOI and MRS relaxation. There were no significant differences between reflexology or massage. There were no significant between group differences in HADS anxiety and depression.Self-reported use of out of study complementary therapies indicated that this was unlikely to have a significant effect on findings. ConclusionsWhen compared to SIS, reflexology and massage have statistically significant, and, for reflexology, clinically worthwhile, effects on QofL following surgery for early breast carcinoma.

Evaluating Minimal Important Differences for the FACT-Melanoma Quality of Life Questionnaire

Minimal Important Differences (MIDs) establish benchmarks for interpreting mean differences in clinical trials involving quality of life outcomes and inform discussions of clinically meaningful change in patient status. The purpose of this study was to assess MIDs for the Functional Assessment of Cancer Therapy-Melanoma (FACT-M). A prospective validation study of the FACT-M was performed with 273 patients with stages I through IV melanoma. FACT-M, Karnofsky Performance Scales, and Eastern Cooperative Oncology Group Performance Status scores were obtained at baseline and 3 months following enrollment. Anchor- and distribution-based methods for assessing MIDs were compared, and pattern-mixture modeling was employed to derive multivariate adjusted estimates. This study indicates that an approximate range for MIDs of the FACT-M subscales is between 5 to 9 points for the Trial Outcome Index, 4 to 6 points for the Melanoma Combined Subscale, 2 to 4 points for the Melanoma Subscale, and 1 to 2 points for the Melanoma Surgery Subscale. Each method produced similar but not identical ranges of MIDs. The properties of the anchor instrument employed to derive MIDs directly affect resulting MID ranges and point values. When MIDs are offered as supportive evidence of a clinically meaningful change, the anchor instrument used to derive clinically meaningful thresholds of change should be clearly stated along with information supporting the choice of anchor instrument as the most appropriate for the domain of interest.

Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with interferon beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after randomisation. Patients and study personnel remained unaware of initial treatment allocation throughout the study. Primary endpoints were time to CDMS, time to confirmed disability progression measured with the expanded disability status scale, and the functional assessment of multiple sclerosis trial outcomes index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment reduced the risk of CDMS by 37% (hazard ratio [HR] 0.63, 95% CI 0.48-0.83; p=0.003) compared with delayed treatment. The risk for confirmed disability progression was not significantly lower in the early treatment group (0.76, 0.52-1.11; p=0.177). At 5 years, median FAMS-TOI scores were 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b. Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with interferon beta-1b, although a delay in treatment by up to 2 years did not affect long-term disability outcomes. Bayer Schering Pharma.

Quality of life and disease-related symptoms in previously treated Japanese patients with non-small-cell lung cancer: results of a randomized phase III study (V-15-32) of gefitinib versus docetaxel

BackgroundThis report describes quality of life (QoL) findings of a randomized study comparing gefitinib with docetaxel in patients with advanced/metastatic pretreated non-small-cell lung cancer. Patients and methodsThis open-label, phase III study randomized 490 Japanese patients to gefitinib (250 mg/day) or docetaxel (60 mg/m2/3 weeks), with survival as the primary outcome. Preplanned QoL analyses included Functional Assessment of Cancer Therapy-Lung (FACT-L), Trial Outcome Index (TOI) and Lung Cancer Subscale (LCS) improvement rates, and mean change from baseline. ResultsGefitinib showed statistically significant benefits over docetaxel in QoL improvement rates (FACT-L 23% versus 14%, P=0.023; TOI 21% versus 9%, P=0.002) and mean change from baseline score [mean treatment difference: FACT-L 3.72 points, 95% confidence interval (CI) 0.55–6.89, P=0.022; TOI 4.31 points, 95% CI 2.13–6.49, P<0.001], although differences did not meet the clinically relevant six-point change. There were no significant differences between treatments in LCS improvement rates (23% versus 20%, P=0.562) or mean change from baseline score (0.63 points, 95% CI -0.07 to 1.34, P=0.077). ConclusionsGefitinib improved aspects of QoL over docetaxel, with superior objective response rate and a more favorable tolerability profile and no statistically significant difference in overall survival (although noninferiority was not statistically proven).

Impact of pegylated liposomal doxorubicin (PLD) plus docetaxel (D) versus single-agent D on health-related quality of life (HRQOL) of patients with advanced breast cancer (BC) previously treated with neoadjuvant-adjuvant anthracycline

e20522 Background: A randomized, multicenter phase 3 trial of PLD+D showed a significant improvement in the primary endpoint of time to progression (TTP) compared with D alone but with increased Grade 3/4 hand-foot syndrome (HFS: 24% vs. 0%) and mucositis/stomatitis (M/S: 12% vs. 1%) in patients (pts) with advanced breast cancer (BC). (Sparano JA et al. SABCS 2008. #80) This analysis evaluated HRQOL in these pts. Methods: Pts were randomized to D 75 mg/m2 (N=373) or PLD 30 mg/m2 + D 60 mg/m2 (N=378) on Day 1 every 21 days until progression or unacceptable toxicity. HRQOL was assessed using the Functional Assessment of Cancer Therapy - Breast (FACT-B) at baseline and at every cycle during treatment. FACT-B has 4 primary domains: physical, social/family, emotional, and functional, plus a BC-specific subscale. The primary analysis was a t-test comparison of change in the trial outcome index (TOI) from baseline to the last evaluation. TOI combined physical/functional domain scores with BC-specific scores. Other FACT-B endpoints analyzed included FACT-B total score and individual subscales. Also, % pts meeting an established minimally important difference (MID) of HRQOL improvement in TOI was assessed. Results: Median number of cycles was 6 for both arms. TOI was available for 97.9% of all scheduled assessments for both treatment groups. At baseline, mean FACT-B and TOI scores were similar for PLD+D vs D arms (94.2±18.6 vs 95.3±18.7 and 59.7±13.8 vs 60.2±13.4, respectively); other FACT-B domains were also similar. PLD+D vs D arms showed similar mean change from baseline to last evaluation in TOI (-4.6±12.2 vs -6.0±12.4; P=0.13). Other FACT-B subscales showed 1–2 point differences across domains over time. Likewise, % pts reaching MID was similar across arms. Pts in both arms experienced similar FACT-B declines as disease progressed. Conclusions: Despite increased HFS and M/S with PLD+D vs D alone, HRQOL was comparable for both arms. [Table: see text]

Plasma cytokine concentrations and quality of life in patients with non-small cell lung cancer in a phase II trial of first-line treatment with carboplatin-paclitaxel and/or vandetanib

9596 Background: A randomized phase II trial (JCO 26:5407–15, 2008) compared carboplatin-paclitaxel (CP) with vandetanib (VEGFR-EGFR inhibitor) monotherapy (V) and V plus CP (VCP) 1st-line for advanced NSCLC (N=181). PFS was superior for VCP vs CP (HR 0.76). We performed analyses of quality of life (QOL) and its correlations with plasma concentrations of cytokines and angiogenic factors (CAF) among the participants in this trial. Methods: QOL was serially measured by Functional Assessment of Cancer Therapy-Lung (FACT-L) and Trial Outcome Index (TOI) scores. Concentrations of 35 plasma CAFs were measured at baseline and multiple timepoints during treatment with multiplexed bead suspension arrays and ELISAs. We performed exploratory analyses for the following associations: (1) QOL with plasma CAF levels at baseline; (2) changes in QOL with changes in plasma CAF levels. Spearman correlation coefficient, log-rank test and mixed linear models were applied in the analyses. P-value &lt; 0.05 was considered significant. Results: Baseline QOL and plasma samples were both available for 120 patients. Lower baseline FACT-L scores (inferior QOL) were associated with higher pre-treatment plasma levels of INF-γ, IL-1RA, IL-6, IL-12, IL-15, TNF-α, RANTES, MIG, MIP-1β, MMP-9, bFGF, VEGF and sVEGFR-2 (all P&lt;0.05). Lower baseline TOI scores (inferior QOL) were also associated with higher pre-treatment plasma levels of multiple CAFs, including GCSF, HGF, INF-α, INF-γ, IL-2, IL-6, IL-8, IL-12, IL-15, TNF-α, bFGF, sVEGFR-2 and VEGF (all P&lt;0.05). Among all patients, decreasing TOI scores post cycle 2 (HR=2.57 [1.28,5.17], P=0.008) and cycle 4 (HR=2.58 [1.01,6.56], P=0.049) were associated with increased progression risk. Trends for FACT-L were similar, but did not reach statistical significance. Rises in GCSF, HGF, IL-2, IL-8, IL-15, MCP-1, MIP-1β, and VEGF from baseline to post cycle 2 were associated with decreased FACT-L and/or TOI scores (all P&lt;0.05). Conclusions: High plasma concentrations of multiple CAFs pre-treatment in patients with NSCLC correlated with inferior QOL, and rises in these factors during treatment were associated with worsening QOL. This work was funded in part by grant from ACS (FK). [Table: see text]

First-line treatment with lapatinib plus paclitaxel versus paclitaxel alone for patients with HER2+ metastatic breast cancer (MBC): Quality-of-life (QOL) analysis using repeated measures and pattern mixture models

1049 Background: A phase III randomized, multicenter, double-blind, placebo-controlled study compared first-line therapy with lapatinib and paclitaxel (L+P) versus paclitaxel alone (P) for MBC. In a sub-group analysis of HER2+ patients, time to tumor progression for L+P was significantly improved, with an emerging trend for survival benefit. This analysis models the QOL data in the subset of the randomized ITT population that overexpressed HER2 (FISH+ or IHC3+). Methods: QOL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. Outcome measures included FACT-B total score, trial outcome index (TOI) score and breast cancer subscale (BCS). Higher scores represent better QOL. Patients completed the FACT-B at the screening visit, week 9, every 12 weeks thereafter, and at discontinuation of therapy. The assessment at discontinuation was applied to the next scheduled visit for analyses. Changes from baseline were analyzed using repeated measures models with baseline score as a covariate. Pattern mixture modeling was implemented as a sensitivity analysis. Results: Of 579 randomized patients, 86 were HER-2+ and 85 completed at least one item from the FACT-B (n = 48 L+P; n = 37 P). The baseline characteristics of this subset were well-matched with regard to age, ECOG status, and prior anthracycline use. More patients in the L+P group than in the P group had visceral disease (69% vs 51%) and more were at stage IV (88% vs 78%).Over the first year, the L+P arm demonstrated stable FACT-B scores over time, whereas average scores for patients on paclitaxel monotherapy decreased (change from baseline: L+P p = 0.99; P p = 0.01). Statistically significant differences were observed between treatment arms on the FACT-B (p = 0.05), TOI (p = 0.03), and BCS (p = 0.01). Pattern mixture models suggested more QOL differentiation between treatments among patients who progressed or withdrew within 6 months of study start. Conclusions: Among patients with HER2+ MBC, treatment with L+P resulted in more stable QOL than with P monotherapy. These findings represent clinically important differences between treatment groups. [Table: see text]

Lapatinib plus letrozole compared with letrozole alone as first-line therapy in hormone receptor positive HER2+ metastatic breast cancer (MBC): A quality-of-life (QOL) analysis

1039 Background: A phase III randomized double-blind multicenter trial compared lapatinib plus letrozole (L+Let) with letrozole plus placebo (Let), as first-line therapy for hormone receptor positive (HR+) MBC. Median PFS, the primary endpoint of the study, in patients who were HER2+ was significantly prolonged for L+Let compared with Let (8.2 vs 3 months, Hazard Ratio (95% CI)=0.71(0.53,0.96), p=0.019). This analysis focuses on the impact of treatments on QOL in the HER2+ subgroup. Methods: QOL outcomes included the Functional Assessment of Cancer Therapy-Breast (FACT-B) total, FACT-general (FACT-G), and trial outcome index (TOI) scores assessed at screening, every 12 weeks and at withdrawal. Higher scores indicate better QOL. Changes from baseline were analyzed using analysis of covariance. In a responder analysis, patients achieving minimally important differences in QOL scores (QOL responders) were compared with Fisher's exact test. Results: Among 1,286 patients, 219 were identified as HER2+ (L+Let n=111; Let n=108). Baseline QOL scores were comparable in the two arms. In this population, mean changes in subscale and total QOL scores were generally stable over time in both treatment arms for patients who stayed on study. For example, on the FACT-B, the average change from baseline in both groups was positive at all scheduled visits through Week 48 and the maximum difference between arms was 2.6 points (CI: -5.8, 11). There were no significant differences between the two treatment arms in percentage of QOL responders (Table). Conclusions: The addition of lapatinib to letrozole significantly increases PFS while maintaining QOL when compared with letrozole alone thus confirming the clinical benefit of the combination therapy in the HR+, HER2+ MBC patient population. This combination provides an effective option in this patient population by maintaining QOL and delaying the need for chemotherapy and its accompanying side effects. [Table: see text] [Table: see text]

Components of early intervention outpatient palliative care consultation in patients with incurable NSCLC

e20635 Background: Many experts recommend palliative care consultation early in the course of oncology treatment; however little is known about the components of this type of intervention. We sought to better define the components of early palliative care consultation in patients with recently diagnosed incurable cancer. Methods: As part of a larger randomized study of integrated versus standard palliative care in an ambulatory thoracic oncology clinic, we analyzed data from 47 patients who received early palliative care consultation within eight weeks of diagnosis of incurable NSCLC with a performance status of 0–2. Prior to randomization, patients completed questionnaires on quality of life (FACT-L) and mood (HADS) as well as illness understanding. The FACT-L Trial Outcome Index which is a combined score of physical, functional well being, and lung cancer symptoms was calculated and used in correlations to more fully assess quality of life. After the consultation, palliative care clinicians recorded how time was spent during the encounter. Results: Seven palliative care clinicians provided consultation to 47 patients. The mean total time spent with each patient was 59.5 minutes (SD 28.6). The major components of each consultation were symptom management 25.7 minutes (SD 15.8), patient and family coping 19.6 minutes (SD 14.7), and illness understanding and education 10.4 minutes (SD 7.6). Greater total consultation time was correlated with poorer performance status (r=0.30, p=0.04) and lower quality of life scores on the FACT-L TOI which is a combined score of physical, functional wellbeing, and lung cancer symptoms (r=0.36, p=0.01). Symptom management time was also correlated with lower quality of life scores on the FACT-L TOI (r-0.52, p&lt;0.001) and higher depression scores on the HADS (r=0.33, p=0.02). Conclusions: Initial palliative care consultation near the time of diagnosis in patients with incurable NSCLC is lengthy and comprised primarily of symptom management, patient and family coping, and illness understanding and education. Patients with poorer performance status and quality of life received longer total time in consultation and in time devoted to symptom management No significant financial relationships to disclose.

Effects of Presurgical Exercise Training on Quality of Life in Patients Undergoing Lung Resection for Suspected Malignancy

The aim of this study was to explore the effects of presurgical exercise training on quality of life (QOL) in patients with malignant lung lesions. Using a single-group prospective design, patients were enrolled in supervised aerobic exercise training for the duration of surgical wait time (mean 59.7 days). Participants completed assessments of cardiorespiratory fitness (peak oxygen consumption) and QOL using the Functional Assessment of Cancer Therapy-Lung scales, including the trial outcome index (TOI) and the lung cancer subscale (LCS) at baseline, immediately presurgery, and postsurgery (mean, 57 days). 9 participants provided complete data. Repeated-measures analysis indicated a significant effect for time on TOI (P = .006) and LCS (P = .009). Paired analysis revealed that QOL was unchanged after exercise training (ie, baseline to presurgery), but there were significant and clinically meaningful declines from presurgery to postsurgery in the LCS (-3.6, P = .021) and TOI (-8.3, P = .018). Change in peak oxygen consumption from presurgery to postsurgery was significantly associated with change in the LCS (r = 0.70, P = .036) and TOI (r = 0.70, P = .035). Exercise training did not improve QOL from baseline to presurgery. Significant declines in QOL after surgery seem to be related to declines in cardiorespiratory fitness. A randomized controlled trial is needed to further investigate these relationships.

Estimating Clinically Meaningful Changes for the Functional Assessment of Cancer Therapy—Prostate: Results from a Clinical Trial of Patients with Metastatic Hormone-Refractory Prostate Cancer

Objective To determine clinically meaningful changes (CMCs) for the Functional Assessment of Cancer Therapy–Prostate (FACT–P). Methods We obtained data from a Phase III trial of atrasentan in metastatic hormone-refractory prostate cancer patients (n = 809). We determined anchor-based differences using Karnofsky Performance Status (KPS), bone alkaline phosphatase (BAP), hemoglobin, time to disease progression (TTP), adverse events (AE), and survival. One-third and one-half standard deviation and standard error of measurement (SEM) were used as distribution-based criteria for CMCs. Comparison across baseline FACT–P domains and derived scales [FACT–P total score, Trial Outcome Index (TOI) score, prostate cancer subscale (PCS) score, pain-related score, and FACT Advanced Prostate Symptom Index (FAPSI)] were conducted for KPS, BAP, and hemoglobin using Student's t tests. Twelve-week change scores were compared for TTP, AE, and survival using ANCOVA. Results CMCs were estimated as 6 to 10 for FACT–P total score, 5 to 9 for FACT–P TOI score, 2 to 3 for FACT–P PCS, 1 to 2 for the 4 PCS pain-related questions, and 2 to 3 for FAPSI. CMCs were also estimated using distribution-based criteria. Kappa statistics were computed to determine the degree of correspondence between the recommended guideline of 1.0 SEM and empirically derived standards. Most of the kappas for health-related quality of life domains and SEM standards had “substantial” to “almost perfect” concordance. Conclusions The significant relationship between clinical and quality of life data provides support for the use of CMCs to increase interpretability of FACT–P scores.

Validation of the Functional Assessment of Cancer Therapy–Lymphoma (FACT-LYM) in Patients with Relapsed/Refractory Mantle Cell Lymphoma

BACKGROUND: The FACT-Lym was developed to assess health-related quality of life (HRQL) in patients with non-Hodgkin's lymphoma (NHL). Cella and colleagues developed the instrument in a general NHL population, including patients with either aggressive or indolent disease (Cella et al, Proc ASH 2005). The current research explores the validity of the FACT-Lym in patients with relapsed/refractory mantle cell lymphoma (MCL) and estimates minimally important differences (MIDs), which can be defined as the smallest change in a patient-reported outcome (PRO) measure that may be perceived as beneficial or result in change in treatment. Data were collected as part of a phase II, single-arm, open-label study of enzastaurin in relapsed/refractory MCL patients (Morschhauser et al, Ann Oncol 2008).METHODS: The FACT-Lym (version 4) was administered prior to the start of therapy, at 2-month intervals while on therapy for up to 6 months, and approximately 30 days after discontinuation. The 30-day discontinuation assessment was commonly associated with disease progression. Descriptive statistics were used to report FACT-Lym scores, with emphasis placed on the lymphoma-specific subscale, the total FACT-Lym, and the Trial Outcome Index (TOI; physical and functional well-being plus lymphoma-specific subscale). Criterion validity was assessed by grouping patients by International Prognostic Index (IPI) (assessed at study entry) and by baseline Eastern Cooperative Oncology Group performance status (PS). Patients were grouped according to changes in:PS (improved/stable or worse) andclinical status from baseline to 30-day discontinuation, to assess the FACT-Lym's responsiveness to change (i.e., ability of an instrument to detect change in clinical status).Analyses included t-tests and one-way analysis of variance (ANOVA). Distribution- and anchor-based methods were used to estimate MIDs. Distribution-based methods included estimates using the standard error of measurement (SEM) and 1/3 or 1/2 standard deviation (SD) approach. Anchors were PS and disease progression.RESULTS: FACT-Lym data were available for 59 of the 60 enrolled patients at baseline and for 40 patients at discontinuation. One patient who did not meet protocol qualifications was excluded from these analyses. The most common reason for missing data was the site failing to administer the instrument. Median age was 66 years, 70% were male, 88% had a baseline PS of 0 or 1, and 52% had an IPI score ≤2. The table below summarizes the baseline and 30-day discontinuation FACT-Lym scores and makes comparisons across IPI and PS scores at baseline. Mean lymphoma subscale, TOI, and total scores were significantly (p<0.05) different between baseline and the 30-day assessment; the differences were −4.8, −10.6, and −11.7 respectively. There was significant difference in the change of the scores from baseline to discontinuation between those patients with improved/stable PS (n=20) and those patients with worsened PS (n=16). For those patients with worsened PS, scores were significantly worse. The estimated MID ranges across the varying methodologies were: lymphoma subscale 2.9–5.4, TOI 5.5–11, and total FACT-Lym 6.5–11.2.CONCLUSIONS: We demonstrated with this retrospective study that the FACT-Lym is valid instrument to assess HRQL in patients with relapsed/refractory MCL. With the FACT-Lym, we were able to differentiate patients based on PS and to measure changes in HRQL associated with worsening health status. IPI was shown to not be a differentiating factor for the FACT-Lym. Despite the limited sample size, these findings are consistent with results from the initial validation work and support the use of the FACT-Lym in patients with MCL. These results can be used to inform future trial designs for relapsed/refractory aggressive lymphoma.FACT-Lym Scores and Comparisons across PS and IPI GroupsLymphoma subscale (0–60)TOI (0–116)Total FACT-Lym (0–168)nMean ± SDp-valueMean ± SDp-valueMean ± SDp-valueBaselineAll patients5846.3 ± 8.8-85.1 ± 16.7-123.9 ± 22.3-PS0.003<0.0010.02202650.2 ± 6.893.0 ± 13.2131.2 ± 19.812544.0 ± 9.281.5 ± 15.8120.6 ± 21.72739.9 ± 7.968.7 ± 16.4105.6 ± 25.4IPI0.4670.2170.587≤22847.0 ± 8.787.8 ± 13.9125.2 ± 20.1≥32645.3 ± 8.982.0 ± 19.5121.8 ± 25.6Discontinuation3942.8 ± 10.7-77.0 ± 22.3-115.0 ± 27.6-

Implications of a Postoperative Rehabilitation Program on Quality of Life in Women with Primary Breast Cancer Treated with Sentinel Lymph Node Biopsy or Complete Axillary Lymph Node Dissection

The aim of this clinical study was to evaluate quality of life (QoL) in early-stage breast cancer patients and to investigate the effects of a comprehensive rehabilitation program comparing women undergoing sentinel node biopsy (SNB) versus complete axillary lymph node dissection (ALND). QoL was assessed with the Functional Assessment of Cancer Therapy--General and Functional Assessment of Cancer Therapy--Breast (FACT-B) questionnaire. Eighty-nine women with histologically confirmed primary breast cancer stages I-II were enrolled. Recruitment began on May 2006 and ended on December 2007. According to current standards of care, 58 women were found clinically fit to undergo SNB, and the other 31 were elected for ALND. Thirty women who underwent SNB were randomly allocated to participate in a comprehensive postoperative rehabilitation program, and the 28 remaining were dismissed and scheduled to return for clinical follow-up. Women undergoing ALND had a better QoL within 30 days of surgery on the FACT-B, FACT-G, Trial Outcome Index (TOI), emotional well-being (EWB), and breast concern subscale (BCS) (P < .005) and at 6 months after surgery on the EWB subscale only. Women undergoing SNB had a significant improvement in QoL only on the EWB subscale 6 months after surgery in the group with rehabilitation and 30 days after surgery in the group without rehabilitation. Women undergoing ALND benefited from a rehabilitation program and had a better QoL. Women undergoing BLS, regardless of rehabilitation, showed improvement in QoL for the emotional well-being subscale only.

Single-Agent Epidermal Growth Factor Receptor Inhibitor Gefitinib for the Treatment of Patients with Advanced Non—Small-Cell Lung Cancer and Poor Performance Status

PurposePatients with advanced non—small-cell lung cancer (NSCLC) have no options for curative therapy; therefore, improving their quality of life (QOL) is also an important treatment goal. Patients with NSCLC and poor performance status (PS) are often excluded from clinical trials. Gefitinib, an epidermal growth factor (EGFR) inhibitor, is a safe oral agent that might benefit these patients. The aim of the study is to evaluate the effect of single-agent EGFR inhibitor gefitinib on the QOL of patients with advanced NSCLC and poor PS. Patients and MethodsNineteen patients with advanced NSCLC and poor PS who were unfit to receive chemotherapy were enrolled on this study of gefitinib 250 mg per day given orally until disease progression. All patients had no previous chemotherapy, an Eastern Cooperative Oncology Group PS of 3, and stage IIIB/IV NSCLC. Response rate, time to disease progression, and overall survival (OS) were calculated. We evaluated the QOL of all eligible patients using the Functional Assessment of Cancer-Lung (FACT-L) questionnaire. FACT-L was used to measure the physical, social/familial, emotional, and functional well-being of the patients as well as lung cancer—specific symptoms and concerns. A Trial Outcome Index (TOI) was derived to assess the physical component of QOL. A mixed-effects linear model was used to examine the effect of potential covariates (age, race, sex, response, and duration of treatment) on the outcome of QOL scores over time. A Cox regression model was used to determine the joint effect of age, race, sex, treatment duration, and baseline TOI score on the OS of the patients. ResultsEleven out of 19 patients were evaluable for this analysis. The median age was 71.8 years (range, 60.9–73.4 years). Six patients had adenocarcinoma, and 5 patients had squamous cell carcinoma, and the median treatment duration was 63.0 days (range, 35–118 days). Grade 3/4 toxicities included fatigue, rash, and diarrhea. One patient had a partial response, 7 patients had stable disease, and 3 patients progressed. The median OS was 5.3 months (range, 2.5–22.1 months), and the median progression-free survival was 3.7 months (range, 2.1–5.8 months). Baseline TOI was weak but significantly associated with OS, with a hazard ratio (HR) of 0.92 (95% CI, 0.85–0.99; P = .03). Duration of treatment was marginally associated with survival, with an HR of 0.98 (95% CI, 0.96–1.0; P = .07). As expected, the total FACT-L score and the TOI were highly correlated (r = 0.96; P < .0001). There were no significant differences in the subscale scores, FACT-General, or the FACT-L between baseline, week 5, and week 8. Notably, an increasing trend of the TOI was observed, ranging from 33.8 at baseline to 42.0 at week 5 to 45.0 at week 8, albeit this trend was not significant. Race and age were significantly associated with the TOI. TOI scores were higher in black patients compared with white patients (P = .03) and increased with age (P = .02). ConclusionSingle-agent EGFR inhibitor gefitinib could be an active and well-tolerated therapy for patients with NSCLC with poor PS, with a trend of the TOI observed for improvement in QOL. Our results suggest that increasing age and black race had higher TOI scores and thus improved QOL status.

Health-Related Quality of Life Impact of Bevacizumab When Combined with Irinotecan, 5-Fluorouracil, and Leucovorin or 5-Fluorouracil and Leucovorin for Metastatic Colorectal Cancer

To compare the time to deterioration in health-related quality of life (HRQoL) in patients with previously untreated metastatic colorectal cancer receiving a 5-fluorouracil (5-FU)-based chemotherapy regimen with or without the addition of bevacizumab (BV) in two randomized, placebo-controlled studies. Prespecified HRQoL endpoints in the phase II (Study 2192) and phase III (Study 2107) studies were time to deterioration in HRQoL, measured by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Colorectal Cancer Subscale (CCS), Trial Outcome Index (TOI-C), and FACT-C total score. Time to deterioration in HRQoL was evaluated for patients with baseline and postbaseline assessments, using the stratified log-rank test. In the pivotal phase III trial, HRQoL baseline and postbaseline CCS scores were available for 127 patients receiving irinotecan, 5-FU, and leucovorin (LV) (IFL) and 122 patients receiving IFL plus BV. The time to deterioration in HRQoL did not differ significantly between treatment groups as measured by the CCS, TOI-C, or FACT-C total score. In the phase II study, baseline and postbaseline CCS scores were available for 77 and 89 patients receiving 5-FU and LV and 5-FU and LV plus BV, respectively. In that study, the time to deterioration in HRQoL was similar between groups as measured by the CCS and TOI-C scores, but was significantly longer in the 5-FU and LV plus BV arm than in the 5-FU and LV plus placebo arm for the FACT-C total score. When added to 5-FU chemotherapy, BV significantly prolonged overall survival and progression-free survival without compromising HRQoL.

Effect of lapatinib plus capecitabine (L+C) on quality of life (QOL) compared to capecitabine (C) alone in ErbB2+ metastatic breast cancer (MBC): An exploratory analysis

9532 Background: In a phase III randomized open-label multicenter trial, L+C improved time to progression and progression free survival vs C alone in women with ErbB2+ MBC who had received prior therapy including trastuzumab. Per-protocol QOL analyses showed higher point estimates for QOL scores for L+C vs C suggesting no detriment to QOL for patients receiving combination therapy. Here we report exploratory QOL analyses. Materials: QOL outcomes included the Functional Assessment of Cancer Therapy-Breast (FACT-B) total, FACT-general (FACT-G), trial outcome index (TOI), EQ-5D utility, and EQ-5D visual analog scale (VAS) scores assessed at screening, every 6 weeks for the first 24 weeks, every 12 weeks thereafter and at study withdrawal. Higher scores indicate better QOL. Analyses included: comparison of proportions of patients achieving clinically important differences (CID) in QOL scores for L+C vs C with Fisher’s exact test; relationship between QOL and tumor response status using analysis of covariance adjusted for baseline score; and Pearson correlation coefficients (r) between QOL change from baseline scores and % tumor size reduction. Results: The study randomized 198 subjects to L+C and 201 subjects to C with nearly 50% completing Week 12 and 20% completing Week 24. A greater proportion of patients receiving L+C vs C achieved the CID for all 5 QOL scores (greater by 3 - 12 % points, although the differences in proportions were not statistically significant). Patients who showed a tumor response had higher adjusted mean QOL change from baseline scores compared to those showing disease progression (significant at Week 12, FACT-B total by 7.3, FACT-G 6.1, TOI 5.7, EQ-5D utility 0.11, and ED-5D VAS 10.7). Also, reductions in tumor sizes were associated with improvement in the 5 QOL scores (ranging from r = 0.15 to 0.19, p = 0.02 to 0.07). Conclusions: A greater proportion of patients receiving lapatinib in combination with capecitabine achieved clinically important improvements in QOL scores versus capecitabine alone. These QOL benefits were positively related to the clinical benefits. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline

A randomized open-label study of gefitinib versus docetaxel in patients with advanced/metastatic non-small cell lung cancer (NSCLC) who have previously received platinum-based chemotherapy

8025 Background: ISTANA [IRESSA as Second-line Therapy in Advanced NSCLC - Korea] study compared gefitinib (250 mg/day orally) with docetaxel (75 mg/m2 iv every 3 weeks) in patients (pts) with advanced or metastatic NSCLC pre-treated with platinum- based chemotherapy. Methods: Between September 2005 and September 2006, 161 pts (62% male, 68% adenocarcinoma, 41% never-smoker) were randomized to receive gefitinib or docetaxel. The primary objective was to compare progression-free survival (PFS) between gefitinib and docetaxel at the 1-sided 5% significance level. Secondary endpoints were overall survival (OS), objective tumor response rates (ORR), quality of life (QoL; Functional Assessment of Cancer Therapy-Lung [FACT-L] total score and Trial Outcome Index), symptom improvement (FACT-L Lung Cancer Subscale [LCS]), and safety and tolerability. PFS and OS were compared between the treatment groups by the log-rank test and by unadjusted Cox proportional hazard (Cox) model and adjusting for sex, histology, smoking, stage, and performance status. Results: PFS was longer for gefitinib compared to docetaxel (1-sided p=0.0441). The Hazard Ratio (HR) for PFS derived from the unadjusted Cox model was 0.729 (90% CI 0.533–0.998), favoring gefitinib. Gefitinib significantly improved ORR (28.1% vs. 7.6%; 2-sided p=0.0007). OS appears to be longer for gefitinib pts compared to docetaxel pts (HR 0.61, 95% CI 0.35–1.05), although the number of events is small; follow-up is ongoing. No significant differences between arms were seen in QoL and symptom improvement rate. Adverse events (AEs) were generally mild and consistent with the underlying disease and toxicity profile previously seen with each treatment. Grade 3/4 AEs occurred in 21.0% (gefitinib) and 27.6% (docetaxel) of pts. There was 1 possible treatment-related death in the gefitinib arm. The incidence of interstitial lung disease-type event was 3.7% (n=3) with gefitinib and 3.9% (n=3) with docetaxel. Conclusions: The primary endpoint of PFS was longer with gefitinib. Gefitinib significantly improved the ORR compared with docetaxel. Gefitinib was broadly similar to docetaxel in terms of overall QoL improvement. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology

Quality-of-life results of a randomized phase III trial of four cisplatin (Cis) containing doublet combinations in stage IVB cervical carcinoma: A gynecologic oncology group (GOG) study

5529 Background: Women with stage IVB, recurrent or persistent cancer not amenable to cure were randomized to Cis (C) plus one of the following four drugs: paclitaxel (CP, Reference Arm); vinorelbine (CV); gemcitabine (CG); or Topotecan (CT). Quality of life (QOL) was evaluated in order to determine if CV, CG, or CT was associated with less neuropathy, less pain, or better QOL relative to CP. Methods: QOL was assessed prior to randomization (baseline), prior to cycles 2 and 5, and 9 months post study entry. QOL measures included the Functional Assessment of Cancer Therapy - Cervix Trial Outcome Index (FACT-Cx TOI), the FACT/GOG-Neurotoxicity 4- item scale, and the Brief Pain Inventory 0–10 pain intensity item. Results: The study was closed in April 2007 based on a planned interim analysis on clinical endpoints. By then, 81.8% of target accrual was enrolled (N=491). There was no statistically significant difference in the completion of QOL forms between groups. Baseline scores were comparable on all measures. From pre-cycle 2 through the 9- month follow-up, there were no clinically or statistically significant differences across any of the groups in pain or QOL. Power to detect a 0.5 SD difference between groups was better than 80% pre-cycle 2, but ranged from 22–67% for the last two assessments. Women on the CG and CT regimens reported less neuropathy at the last two assessments, although the difference was not statistically significant. In general, QOL and pain improved slightly over time and neuropathy worsened, showing no indication of improving at the 9-month assessment. Conclusions: No doublet was clinically or statistically different from CP in QOL or pain. A clinical advantage to CG and CT treatment is possible with regard to neurotoxicity, but low power might contribute to a lack of statistical significance. The survival and QOL data will be fully mature in spring 2008, providing more context for interpretation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline

Time to deterioration in dimensions of health-related quality of life (HRQL) for patients with recurrent glioblastoma multiforme (GBM): Results from the randomized, phase III trial of enzastaurin (ENZ) versus lomustine (CCNU)

2040 Background: One goal of therapy for recurrent GBM is to delay worsening in HRQL, with interventions expected to have greatest impact on physical and functional domains. HRQL assessment in recurrent GBM has been limited by deterioration of patient (pt) status. We report HRQL results from a multinational phase III trial. Methods: Pts with recurrent GBM were randomized 2:1 to ENZ 500 mg daily or CCNU 100–130 mg/m2 every 6 weeks. Pts and proxies completed the 50-item Functional Assessment of Cancer Therapy - Brain (FACT-Br) (version 4) prior to randomization, approximately every 3 weeks while on therapy and then 30 days after discontinuation. Time to deterioration (TtD) for each pt was defined as an 11-point decrease in the 148-point Trial Outcome Index (TOI; physical and functional well-being plus brain tumor-specific concerns) or death. Only pts with baseline FACT-Br data were included in the analysis. Proxy data were used when pts were unable to complete the FACT-Br and if there were sufficient dyad data to establish an imputation pattern. TtD was analyzed using Kaplan-Meier methods. To assess differences between arms in TOI subscales, change from baseline was analyzed with a mixed-effects analysis of variance model. Results: Enrollment was terminated after an interim analysis. Of 266 randomized pts, 159 / 174 (91%) ENZ and 82 / 92 (89%) CCNU pts were analyzed for TtD. Baseline scores for TOI were not statistically different between arms (p=0.638). Pt compliance for completing the FACT-Br on-study over the first 6 months was 77% for ENZ and 78% for CCNU; use of proxy data increased compliance to 79% and 81%, respectively. Median TtD was 2.27 months for ENZ and 2.33 months for CCNU with 6-month rates of 18% and 29%, respectively (hazard ratio = 1.12 [95% CI: 0.77–1.63]; log-rank p-value = 0.54; 47% censoring). There were no differences between arms in change from baseline in physical and functional well-being or in brain tumor-specific concerns (p>0.05). Conclusions: Assessment of HRQL is feasible in pts with recurrent GBM. No difference in time that physical and functional domains of HRQL were maintained was detected between ENZ and CCNU. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly, MGI Pharma, Pfizer Oncology, Schering-Plough Eli Lilly Eli Lilly, Merck, Pfizer Oncology, Schering-Plough Eli Lilly Schering-Plough