Are changes in patient-reported outcomes prognostic for diffuse large B-Cell lymphoma survival? Results from the GOYA trial.

In this hypothesis-generating analysis, we examined whether longitudinal changes in patient-reported outcomes (PROs), such as symptoms, over time would be prognostic for progression-free survival (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who were newly treated with obinutuzumab (G) in combination with CHOP (G-CHOP) or rituximab (R) with CHOP (R-CHOP), in the GOYA Phase 3 trial (NCT01287741). Our results show that from the study baseline to cycle 3 day 1, every 1-point increase (worsening) in fever symptoms was associated with a 41% higher risk of death (hazard ratio [HR], 1.41; P = 0.01). Every 1-point increase (worsening) in lumps or swelling symptoms was associated with a 27% higher risk of disease progression or death (PFS events) (HR, 1.27; P = 0.01) and a 29% higher risk of death (OS events) (HR, 1.29; P = 0.02). No significant associations were observed between survival and changes in other symptoms, such as itching. Our study suggests that changes in some PROs are related to survival in DLBCL patients.

Psychometrics of patient-reported bother from side effects of treatment single-items in industry-sponsored oncology trials.

BACKGROUND: Improvements in cancer treatment have increased the number of cancer survivors, but also increased the long-term and late effects from cancer therapy. Patient reported "side effect bother" could be used to measure the burden of treatment, and the risk for negative outcomes such as dose reduction, treatment delay or discontinuation. The current study addresses the psychometric properties of a single item, determines what represents a "meaningful change", and evaluates the correlation to safety endpoints and functioning. METHODS: Results from 5911 patients enrolled in 8 clinical trials representing 5 disease types in oncology and hematology who completed either the Functional Assessment of Cancer Therapy (FACT) GP5 item or a modified bother item (MBI) were assessed. RESULTS: Patients ranged in age from 18 to 93 years, with all cancer stages represented and approximately equal numbers of males and females. Test-retest reliability was acceptable, as were convergent and known groups validity. The GP5 and MBI effectively demonstrated sensitivity to change over time and established meaningful thresholds. CONCLUSIONS: The results indicate that these single-items are psychometrically sound, capable of distinguishing known groups, responsive to change and can identify meaningful change over time in terms of treatment-related symptoms. It extends the findings of recent scientific groups by providing analyses not included in prior studies, and further supports the FDA's recommendation to include a single item question in clinical trials.

Patient-reported outcomes provide prognostic information for survival in patients with diffuse large B-cell lymphoma: Analysis of 1239 patients from the GOYA study.

PURPOSE: We investigated the prognostic value of pretreatment patient-reported outcomes (PROs) in patients with diffuse large B-cell lymphoma (DLBCL) receiving obinutuzumab/rituximab plus chemotherapy in the GOYA phase III study. METHODS: Patients completed the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) and the Functional assessment of chronic illness therapy-Lymphoma (FACT-Lym) lymphoma subscale (LYMS) during the study. PRO scales with high prognostic value were identified through Cox regression analyses of overall survival (OS) and progression-free survival (PFS). These scales were evaluated in terms of their additional prognostic value beyond the International Prognostic Index (IPI). A preliminary assessment was performed to evaluate whether the scales provided improved patient-risk stratification beyond IPI. RESULTS: One thousand two hundred and fifty-nine patients with valid pretreatment PRO scales were included in the analyses, and complete pretreatment data were available for 1239/1414 patients (87.6%). Four PRO scales with high prognostic value were identified: FACT-Lym LYMS and EORTC QLQ-C30 physical functioning, global health status/quality of life (QoL), and fatigue. All four scales retained significant prognostic value for OS and PFS after IPI adjustment (all p < 0.05). After adjusting for multiple clinical variables (IPI, cell of origin, BCL2 status, and total metabolic tumor volume), all four scales retained significant prognostic value (all p < 0.05) for OS. Only the EORTC QLQ-C30 physical functioning scale was significant (p < 0.05) for PFS after adjustment for multiple clinical variables. CONCLUSIONS: In this large population of patients with DLBCL, pretreatment PROs provided prognostic information for OS and PFS beyond the well-established IPI.

Improvements in Health-related Quality of Life and Symptoms in Patients With Previously Untreated Chronic Lymphocytic Leukemia: Final Results From the Phase II GIBB Study of the Combination of Obinutuzumab and Bendamustine.

BACKGROUND: We evaluated health-related quality of life (HRQoL) in patients with chronic lymphocytic leukemia (CLL) receiving first-line chemoimmunotherapy in the GIBB single-arm, Phase II study of obinutuzumab plus bendamustine (BG). MATERIALS AND METHODS: Patients received six 28-day cycles of BG and were followed for up to 27 months. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) and EORTC QLQ Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) questionnaires. Scores were linear-transformed to a 100-point scale, with clinically meaningful responses defined as a ≥ 10-point change from baseline. RESULTS: The patient-reported outcome (PRO) population comprised 98 patients (68.4% male; median age 61 years). EORTC QLQ-C30 global health status improvements were noted at all follow-up visits and were clinically meaningful 2 to 3 months after induction and at 3- and 27-months' follow-up. Clinically meaningful improvements were also observed for the EORTC QLQ-C30 role functioning, emotional functioning, fatigue and insomnia scales and the EORTC QLQ-CLL16 fatigue, disease symptoms and future health worries scales. Global health status was maintained throughout follow-up, and no clinically relevant deterioration in other HRQoL parameters was observed. CONCLUSION: PRO data from the GIBB study show improved overall HRQoL in patients with CLL who received first-line chemoimmunotherapy with BG.

Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events: Methods for item selection in industry-sponsored oncology clinical trials.

As new cancer treatment regimens demonstrate increased potential to improve patients' survival, more focus is directed toward the quality of that extension of life and to obtaining additional information from patients regarding their experience with treatment. The utility of capturing patient-reported treatment-related symptoms to complement traditional clinician-rated symptomatic adverse event reporting is well-documented. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library aimed at capturing patient-reported symptoms to inform the patient perspective on a treatment's tolerability. The U.S. Food and Drug Administration has recommended using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in clinical trials. A practical guideline is needed to inform a priori selection of specific Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items for use in any given industry-sponsored oncology clinical trial. Standardizing this selection process will foster systematic and consistent data collection as part of drug development and enhance our knowledge on how to use patient-relevant information as part of a treatment's risk/benefit assessment. This article presents methods and consensus recommendations for selecting specific Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items to include in early-phase and late-phase oncology clinical trials.

Health-related quality of life and symptoms in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated in the phase III GADOLIN study with obinutuzumab plus bendamustine versus bendamustine alone.

We present health-related quality of life (HRQoL) data from GADOLIN, comparing bendamustine (B) alone or combined with obinutuzumab (G-B) in rituximab-refractory indolent non-Hodgkin lymphoma patients. The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire was administered on day 1 of cycles 1, 3, and 5 during treatment, at end of induction (EOI), bi-monthly for 2 years during maintenance/follow-up, and annually during extended follow-up until progression/death. Time to first ≥6-point worsening from baseline in the FACT-Lym trial outcome index (TOI) was estimated. Minimally important differences at individual subscale and total score level were used to define the proportion of patients reporting improvement on the FACT-Lym lymphoma-specific subscale (≥3 points), FACT-Lym TOI (≥6 points), and FACT-Lym total score (≥7 points). Overall, 396 patients were randomized. Analysis was conducted when 175 Independent Review Committee-assessed progression-free survival (PFS) events were observed. Questionnaire completion rates were generally balanced between arms at baseline, EOI, and final follow-up. Median time to ≥6-point worsening from baseline on the FACT-Lym TOI was 8.0 months in the G-B arm and 4.6 months in the B arm (HR 0.74; 95% CI 0.56-0.98). More G-B patients reported meaningful improvements on the FACT-Lym questionnaire subscales. Results were similar when follicular lymphoma patients were analyzed separately. The delayed time to worsening and greater proportion of patients reporting meaningful improvement in HRQoL in the G-B arm suggest that benefit in PFS is not at the expense of an increase in treatment-related toxicity that could lead to reduced HRQoL.

Randomized controlled trials in relapsed/refractory follicular lymphoma: a systematic review and meta-analysis.

This systematic literature review evaluated the clinical efficacy and safety of interventions used in relapsed/refractory follicular lymphoma. Primary efficacy outcomes were objective response rate, progression-free survival and overall survival. Safety endpoints were grade 3/4 toxicities, serious adverse events and withdrawals or deaths due to toxicity. Studies were selected if they were randomized controlled trials reporting on the efficacy or safety of treatments for relapsed or refractory follicular lymphoma, and if outcomes were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 10 randomized controlled trials of treatments for relapsed/refractory follicular lymphoma. The most prominent drug investigated (alone or in combination) was rituximab. Most trials did not report median overall survival. Two trials reported median event-free survival (range, 1.2-23.2 months). Six of ten trials reported objective response rate (range, 9-93%). Meta-analysis showed only one statistically significant result: rituximab + bortezomib yielded a significantly higher objective response rate than rituximab monotherapy (relative risk, 1.28; 95% confidence interval, 1.11-1.47). Otherwise, there were no discernable differences in overall survival or progression-free survival, partly due to insufficient reporting of results in the clinical trials. The relatively small number of randomized controlled trials, few overlapping treatment arms, and variability in the randomized controlled trial features and in the endpoints studied complicate the formal comparison of therapies for relapsed/refractory follicular lymphoma. Additional well-designed randomized controlled trials are needed to fully understand the relative outcomes of older and more recently developed therapies.

Randomized controlled trials in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis.

This systematic literature review with meta-analysis was conducted on the clinical efficacy and safety of interventions used in the treatment of chronic lymphocytic leukemia (CLL). We systematically searched databases (PubMed, Cochrane Library, and Embase; 1997 to August 2, 2012), conference abstracts, bibliographic reference lists, recent reviews, and Clinicaltrials.gov. Primary efficacy outcomes were objective response rate, progression-free survival, and overall survival. Safety end points were Grade 3/4 toxicities, serious adverse events, withdrawals because of toxicity, and deaths due to toxicity. Studies were selected if they were randomized controlled trials (RCTs) reporting on the efficacy or safety of relapsed or refractory CLL and if outcomes for CLL were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 6 RCTs of pharmacologic treatment for relapsed/refractory CLL. The most common drugs investigated (alone or in combination) were fludarabine and cyclophosphamide. When reported, median overall survival ranged from 27.3 to 52.9 months, and overall response rate from 58% to 82%. Although meta-analysis of efficacy results was considered, details are not presented because only 3 studies qualified and the common comparator treatment was not clinically relevant. The relatively small number of RCTs, few overlapping treatment arms, and variability in end points studied make it difficult to formally compare therapies for relapsed/refractory CLL. Significant variability in RCT features presents a further challenge to meaningful comparisons. Additional well-designed RCTs are needed to fully understand the relative efficacy and safety of older and more recently developed therapies.

Clinical efficacy and safety in relapsed/refractory mantle cell lymphoma: a systematic literature review.

A systematic literature review was performed to collect and review information on the clinical efficacy and safety of treatments for relapsed/refractory (R/R) mantle cell lymphoma (MCL), with a meta-analysis, if possible. PubMed, Embase, and the Cochrane Library were searched for studies published in English from January 1, 1997, to August 2, 2012. Conference proceedings, bibliographic reference lists of included articles, recent reviews, and ClinicalTrials.gov were searched for phase II to IV studies displaying results. Studies were included if they reported on patients with R/R MCL who were ineligible to receive high-dose chemotherapy with stem cell transplant. Studies of patients with several non-Hodgkin lymphoma subtypes were only included if they reported MCL outcomes separately. We identified 59 studies in R/R MCL. Forty distinct treatment regimens were evaluated. Thirty studies included more than 15 patients with R/R MCL. Six studies were comparative (including 5 randomized controlled trials [RCTs]); 53 were single-arm. There were no common treatments among the RCTs; therefore, a meta-analysis was not feasible. Thirty-one of 59 studies reported baseline data for patients with R/R MCL. Of the 30 studies with > 15 patients with R/R MCL, 30 reported overall response rate data, 14 reported progression-free survival (PFS), and 12 reported overall survival (OS). The small number of RCTs in R/R MCL precludes identifying an optimal treatment. Small sample sizes, infrequent reporting of OS and PFS, and limited information on patient characteristics made a comparison of results difficult. High-quality comparative studies of novel therapies that have the potential to demonstrate OS advantages in R/R MCL are needed.

Clinical efficacy and safety in relapsed/refractory diffuse large B-cell lymphoma: a systematic literature review.

This systematic literature review was designed to assess information on the clinical efficacy and safety of interventions used in the treatment of refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL) and to perform a meta-analysis if possible. We searched databases (PubMed, EMBASE, and Cochrane Library for articles from 1997 to August 2, 2012 reported in English), conference abstracts, bibliographic reference lists, and the ClinicalTrials.gov database for phase II to IV studies with results. Studies had to report on patients with R/R DLBCL who were not eligible to receive high-dose therapy (HDT) with stem cell transplantation (SCT) (autologous or allogeneic). Mixed-type non-Hodgkin lymphoma (NHL) studies were required to report R/R DLBCL outcomes separately. We identified 55 studies that presented outcomes data separately for patients with R/R DLBCL. Of 7 comparative studies, only 4 were randomized controlled trials (RCTs). In the 2 RCTs with a common regimen, the patient populations differed too greatly to perform a valid meta-analysis. The 48 single-arm studies identified were typically small (n < 50 in most), with 31% reporting median progression-free survival (PFS) or overall survival (OS) specifically for the R/R DLBCL population. In these studies, median OS ranged from 4 to 13 months. The small number of RCTs in R/R DLBCL precludes identifying optimal treatments. Small sample size, infrequent reporting of OS and PFS separated by histologic type, and limited information on patient characteristics also hinder comparison of results. Randomized studies are needed to demonstrate which current therapies have advantages for improving survival and other important clinical outcomes in patients with R/R DLBCL.

Randomized clinical trial of a brief and extensive dyadic intervention for advanced cancer patients and their family caregivers.

BACKGROUND: Few intervention programs assist patients and their family caregivers to manage advanced cancer and maintain their quality of life (QOL). This study examined (i) whether patient-caregiver dyads (i.e., pairs) randomly assigned to a brief or extensive dyadic intervention (the FOCUS Program) had better outcomes than dyads randomly assigned to usual care and (ii) whether patients' risk for distress and other factors moderated the effect of the brief or extensive program on outcomes. METHODS: Advanced cancer patients and their caregivers (N = 484 dyads) were stratified by patients' baseline risk for distress (high versus low), cancer type (lung, colorectal, breast, or prostate), and research site and then randomly assigned to a brief (three-session) or extensive (six-session) intervention or control. The interventions offered dyads information and support. Intermediary outcomes were appraisals (i.e., appraisal of illness/caregiving, uncertainty, and hopelessness) and resources (i.e., coping, interpersonal relationships, and self-efficacy). The primary outcome was QOL. Data were collected prior to intervention and post-intervention (3 and 6 months from baseline). The final sample was 302 dyads. Repeated measures MANCOVA was used to evaluate outcomes. RESULTS: Significant group by time interactions showed that there was an improvement in dyads' coping (p < 0.05), self-efficacy (p < 0.05), and social QOL (p < 0.01) and in caregivers' emotional QOL (p < 0.05). Effects varied by intervention dose. Most effects were found at 3 months only. Risk for distress accounted for very few moderation effects. CONCLUSIONS: Both brief and extensive programs had positive outcomes for patient-caregiver dyads, but few sustained effects. Patient-caregiver dyads benefit when viewed as the 'unit of care'.

Health-related quality of life in chronic myeloid leukemia.

The increased survival associated with treatments for CML emphasize the importance of understanding the HRQOL of newly diagnosed and previously treated CML patients with all phases of disease. Functional Assessment of Cancer Therapy-Leukemia results from a phase 3 and a phase 2 trial are reported for over 900 1st, 2nd, 3rd line CP, AP, and BP patients. Physical Well-being and Leukemia symptoms were worse for patients in later lines of therapy. Individuals with AP and BP CML had poorer HRQOL than individuals with CP CML. HRQOL of CML patients was predominantly consistent with the longitudinal clinical trajectory of the disease.

Patterns and prognostic indicators of response to CML treatment in a multi-country medical record review study.

We conducted a review of patient medical records to assess treatment response patterns and prognostic indicators of response among chronic myeloid leukemia (CML) patients in the United States, the United Kingdom, Germany, and Japan. All 1,063 patients selected met the following inclusion criteria: aged 18 or older and in chronic phase at the time of diagnosis, Philadelphia chromosome and/or BCR-ABL positive, received first-line treatment with imatinib, and not enrolled in a randomized clinical trial during the period of retrospective review. Multivariable logistic regression models were used to evaluate prognostic indicators of complete hematological response (CHR), complete cytogenetic response (CCyR), and complete or major molecular response (C/MMR). Among patients treated with first-line imatinib, CHR at three months, CCyR at 12 months, and C/MMR at 18 months were observed in 53, 53.1, and 57.8 % of patients, respectively. Among patients treated with second-line dasatinib or nilotinib, CHR was achieved at three months in 49 and 42 %, CCyR at 12 months in 32 and 23 %, and MMR at 18 months in 30.5 and 26.1 % of patients, respectively. Prognostic indicators of first-line response included age, race, and Sokal score. For second-line treatment, duration of first-line hematological response and choice of drug used were also significant.

Patient characteristics and treatment patterns in chronic myeloid leukemia: evidence from a multi-country retrospective medical record chart review study.

We conducted a retrospective medical record review of 1,063 patients to examine patient characteristics and treatment patterns among adults with Philadelphia chromosome and/or BCR-ABL-positive chronic-phase chronic myeloid leukemia in the USA, UK, Germany, and Japan. Patients who were included received first-line treatment with imatinib between 1 January 2005 and 31 December 2009 and were not enrolled in a randomized clinical trial between first-line treatment initiation and end of recorded follow-up. The average age was 55 years; 60% were male. On average, patients were initiated on imatinib 2.7 months post-diagnosis and received therapy for 22 months [19 months (USA) to 25 months (Japan)], at a median dose of 400 mg/day. Thirteen percent [8% (Japan) to 16% (UK)] had dose escalation to a median 800 mg/day. Twenty-nine percent discontinued imatinib, primarily due to resistance or disease progression. Among 148 patients receiving second-line dasatinib and 113 receiving nilotinib, a greater proportion in the USA and Germany received nilotinib (54% in each country), while fewer patients in Japan and the UK received nilotinib (47 and 17%, respectively). On average, patients had second-line therapy initiated 25 months post-diagnosis and received treatment for 11 months (dasatinib) or 8 months (nilotinib). Patients initiating dasatinib had more advanced disease than those initiating nilotinib.

Health-related quality of life of bosutinib (SKI-606) in imatinib-resistant or imatinib-intolerant chronic phase chronic myeloid leukemia.

Understanding the impact of second-line tyrosine kinase inhibitor therapy on the health-related quality of life (HRQOL) of imatinib (IM)-resistant and IM-intolerant chronic phase chronic myeloid leukemia (CP CML) patients is important given the increased survival that comes with therapy. As part of a bosutinib single-arm phase 2 trial, 200 IM-resistant and 88 IM-intolerant CP CML patients' HRQOL was assessed prior to and throughout treatment with the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Little HRQOL impairment was demonstrated at baseline. Over the course of 96 weeks on bosutinib therapy, patients noted statistically significant and/or clinically meaningful improvements on several FACT-Leu scales.

Baseline patient-reported kidney cancer-specific symptoms as an indicator for median survival in sorafenib-refractory metastatic renal cell carcinoma.

INTRODUCTION: The goal of the study was to determine the relationship of baseline Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI) scores with median progression-free survival (mPFS) and median overall survival (mOS) after treatment with axitinib in patients with sorafenib-refractory metastatic renal cell carcinoma. METHODS: As part of a multicenter, open-label, phase II study, patients (N = 62) reported symptoms at baseline using the FKSI, with higher scores indicating less severe symptoms. A Weibull (fully parametric) model was fit to time-to-event data to establish the relationship of baseline FKSI score with mPFS and mOS. Kaplan-Meier curves were obtained as sensitivity analyses. RESULTS: Longer progression-free and overall survivals were associated with higher (more favorable) baseline FKSI-15 and FKSI disease-related symptoms (FKSI-DRS) subscale specific to kidney cancer scores. For example, for FKSI-15 scores of 0 (most symptoms), 30, and 60 (no symptoms), the mPFS were 0.72, 3.83, and 20.43 months, respectively, and the mOS were 1.05, 6.27, and 37.53 months. Similar patterns and interpretations were observed for the FKSI-DRS scores. The results from the Kaplan-Meier analyses supported the parametric model. DISCUSSIONS/CONCLUSIONS: Baseline patient-reported kidney cancer symptoms are linked to mPFS and mOS in a clear and interpretable way. These results support the evaluation of patient-reported symptoms at baseline in clinical trials and in clinical practice to measure symptom severity and potentially predict progression-free and overall survival outcomes. IMPLICATIONS FOR CANCER SURVIVORS: The results provide a heightened opportunity to use patient data not only to assist in medical treatment planning but also to prepare patients, who have advanced disease and an already reduced expected lifespan, with an opportunity to deal with the psychosocial aspects of the dying process.

Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study.

BACKGROUND: Axitinib is a potent, selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. A randomised phase 2 trial of gemcitabine with or without axitinib in advanced pancreatic cancer suggested increased overall survival in axitinib-treated patients. On the basis of these results, we aimed to assess the effect of treatment with gemcitabine plus axitinib on overall survival in a phase 3 trial. METHODS: In this double-blind, placebo-controlled, phase 3 study, eligible patients had metastatic or locally advanced pancreatic adenocarcinoma, no uncontrolled hypertension or venous thrombosis, and Eastern Cooperative Oncology Group performance status 0 or 1. Patients, stratified by disease extent (metastatic vs locally advanced), were randomly assigned (1:1) to receive gemcitabine 1000 mg/m(2) intravenously on days 1, 8, and 15 every 28 days plus either axitinib or placebo. Axitinib or placebo were administered orally with food at a starting dose of 5 mg twice a day, which could be dose-titrated up to 10 mg twice daily if well tolerated. A centralised randomisation procedure was used to assign patients to each treatment group, with randomised permuted blocks within strata. Patients, investigators, and the trial sponsor were masked to treatment assignments. The primary endpoint was overall survival. All efficacy analyses were done in all patients assigned to treatment groups for whom data were available; safety and treatment administration and compliance assessments were based on treatment received. This study is registered at ClinicalTrials.gov, number NCT00471146. FINDINGS: Between July 27, 2007, and Oct 31, 2008, 632 patients were enrolled and assigned to treatment groups (316 axitinib, 316 placebo). At an interim analysis in January, 2009, the independent data monitoring committee concluded that the futility boundary had been crossed. Median overall survival was 8·5 months (95% CI 6·9-9·5) for gemcitabine plus axitinib (n=314, data missing for two patients) and 8·3 months (6·9-10·3) for gemcitabine plus placebo (n=316; hazard ratio 1·014, 95% CI 0·786-1·309; one-sided p=0·5436). The most common grade 3 or higher adverse events for gemcitabine plus axitinib and gemcitabine plus placebo were hypertension (20 [7%] and 5 [2%] events, respectively), abdominal pain (20 [7%] and 17 [6%]), fatigue (27 [9%] and 21 [7%]), and anorexia (19 [6%] and 11 [4%]). INTERPRETATION: The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer. These results add to increasing evidence that targeting of VEGF signalling is an ineffective strategy in this disease. FUNDING: Pfizer.

Does recall period have an effect on cancer patients' ratings of the severity of multiple symptoms?

CONTEXT: Choosing an appropriate recall period for symptom assessment in a clinical trial is dependent on the design and purpose of the trial. OBJECTIVE: To examine the effects of recall on symptom severity ratings by comparing ratings made using 24-hour and seven-day recall periods of the MD Anderson Symptom Inventory (MDASI). METHODS: Forty-two patients in their third to eighth week of chemoradiation rated their symptoms using the MDASI on two separate occasions (T1 and T2), one week apart. At T1, patients were randomly assigned to rate symptoms using either a 24-hour or a seven-day recall. At T2, patients rated symptoms using the recall period not used at their first visit. RESULTS: Comparing the 24-hour and seven-day recall periods, the correlation coefficient for total symptom severity was 0.888. All correlation coefficients for symptom severity items were >0.7 except for distress (r=0.67). The percentages of moderate to severe symptoms (rated >or=5) were consistent for both recall periods, with no significant difference between recall periods in the prevalence of moderate to severe symptoms. Cronbach alpha coefficients for both 24-hour and seven-day recalls were >0.8. Symptoms from both recall periods were more severe for patients with poorer performance status. Twenty patients were cognitively debriefed; 70% thought that the seven-day recall was "more appropriate" for the MDASI, but 85% did not think that recall period would influence their answers. CONCLUSION: This study demonstrated that the MDASI in a seven-day recall format has psychometric properties consistent with the 24-hour recall version, which may promote its use in future cancer clinical trials and may inform the choice of recall period when symptoms are outcome measures.

Psychological distress in patients with pancreatic cancer--an understudied group.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, unsuccessful in significantly improving 5-year survival. A diagnosis of pancreatic cancer may be associated with increased psychological distress, yet remarkably little is known about the degree of psychological distress experienced by these patients at the time of diagnosis and treatment. METHOD: In a cross-sectional study, 304 patients with pancreatic cancer and 7749 patients with other cancer diagnoses completed the Brief Symptom Inventory (BSI) or the Brief Symptom Inventory-Shortened Version (BSI-18) and the Problem Common Checklist (PCL) during outpatient registration. Sociodemographic characteristics were collected from patients' clinical files. RESULTS: A higher percentage of pancreatic cancer patients reported elevated distress across each subscale of the BSI and BSI-18 when compared with those diagnosed with other cancer diagnoses as a group. The most notable difference was established on the depression subscale, with 28.8% of pancreatic patients reporting elevated depression compared with 18.5% of other cancer diagnoses. In pancreatic patients, a significant difference was also found in the percentage of males endorsing high depression levels when compared with females (34.0 vs 22.6%, p<0.05). CONCLUSIONS: Pancreatic cancer patients demonstrate elevated levels of psychological distress. This should alert providers to be vigilant in evaluating patients for distress and to provide appropriate referrals. The endorsement of fatigue and pain, along with the observed gender differences, suggest that early distress management interventions may need to include components targeted to these issues.