Standard Treatment For Elderly Patients Research Articles

App-based assessment of memory functions in patients after transfemoral aortic valve replacement.

Transfemoral aortic valve replacement (TAVR) is the standard treatment for elderly patients with aortic valve stenosis. Although safe and well-established, there is a risk of intraprocedural hemodynamic instability and silent cerebral embolism, which can lead to a decline in neurocognitive function and dementia. In clinical practice, comprehensive cognitive testing is difficult to perform. AI-assisted digital applications may help to optimize diagnosis and monitoring. Neurocognitive function was assessed by validated psychometric tests using "∆elta -App", which uses artificial intelligence and computational linguistic methods for extraction and analysis. Memory function was assessed using the 'Consortium to Establish a Registry for Alzheimer's Disease' (CERAD) word list and digit span task (DST) before TAVR and before hospital discharge. The study is registered in the German Register of Clinical Trials (https://drks.de/search/de/trial/DRKS00020813). From October 2020 until March 2022, 141 patients were enrolled at University Hospital Heart Centre Brandenburg. Mean age was 81 ± 6 years, 42.6% were women. Time between the pre- and post-interventional test was on average 6 ± 3 days. Memory function before TAVR was found to be below average in relation to age and educational level. The pre-post TAVR comparison showed significant improvements in the wordlist repeat, P < 0.001 and wordlist recall test of CERAD, P < 0.001. There were no changes in the digital span test. Despite impaired preoperative memory function before TAVR, no global negative effect on memory function after TVAR was detected. The improvements shown in the word list test should be interpreted as usual learning effects in this task.

Combination of a New Oral Demethylating Agent, OR2100, and Venetoclax for Treatment of Acute Myeloid Leukemia.

The standard treatment for elderly patients with AML is Ven combined with HMAs. OR21, a new oral HMA plus Ven showed synergistic antileukemia effects in vitro and vivo, suggesting that the combination of OR2100 plus Ven is a promising candidate oral therapy for AML.

ACT-8 A RANDOMIZED PHASE III STUDY OF HYPOFRACTIONATED RADIOTHERAPY COMBINED WITH TEMOZOLOMIDE IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: JCOG1910 (AGEDGLIO-PIII)

Abstract Background The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy (40 Gy in 15 fractions) with temozolomide. Further reduction of fractionation is expected to reduce the burden for elderly patients without decreasing therapeutic efficacy. Methods This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant and adjuvant temozolomide in terms of overall survival (OS) in elderly patients aged 71 or older with newly diagnosed glioblastoma. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. MGMT promoter methylation was included as an adjustment factor, and tumor specimen have been collected soon after the tumor resection and molecular diagnosis has been made centrally before randomization. A total of 270 patients will be accrued from 55 Japanese institutions in 4 years and follow-up will last 2 years. Results More than a half of patients (160 /270 cases) have been recruited between August 2020 and July 2022. Molecular diagnosis was made all but one cases, and diagnosis was made centrally within around 7 days after receiving the tumor specimen. There were one grade 4 severe adverse event and one treatment related death. Discussion Registration has been made smoothly without substantial delay due to central molecular diagnosis. The study has been safely performed for elderly patients. If the primary endpoint is met, hypofractionated radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma.

A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)

BackgroundThe current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved.MethodsThis multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71–75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020.DiscussionIf the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma.Trial registrationRegistry number: jRCTs031200099.Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020.

The ACURATE neo2 valve system for transcatheter aortic valve implantation: 30-day and 1-year outcomes

BackgroundTranscatheter aortic valve implantation (TAVI) has become standard treatment for elderly patients with symptomatic severe aortic valve stenosis. The ACURATE neo AS study evaluates 30-day and 1-year clinical and hemodynamic outcomes in patients treated with the ACURATE neo2 valve.MethodsThe primary endpoint of this single-arm multicenter study is 30-day all-cause mortality. Other key endpoints include device performance, echocardiographic measures assessed by an independent core laboratory, and VARC-2 clinical efficacy and safety endpoints through 12 months.ResultsThe study enrolled 120 patients (mean age 82.1 ± 4.0 years; 67.5% female, mean baseline STS score 4.8 ± 3.8%). The VARC-2 composite safety endpoint at 30 days occurred in 13.3% of patients. All-cause mortality was 3.3% at 30 days and 11.9% at 1 year. The 30-day stroke rate was 2.5% (disabling stroke 1.7%); there were no new strokes between 30 days and 12 months. The rate of permanent pacemaker implantation was 15.0% (18/120) at 30 days and 17.8% (21/120) at 1 year. No patients required re-intervention for valve-related dysfunction and there were no cases of valve thrombosis or endocarditis. Patients demonstrated significant improvement in mean aortic valve gradient (baseline 38.9 ± 13.1 mmHg, 1 year 7.8 ± 3.5 mmHg; P < 0.001 in a paired analysis). In the overall population, paravalvular leak was evaluated at 1 year as none/trace in 60.5%, mild in 37.0%, and moderate in 2.5%; no patients had severe PVL.ConclusionsOne-year outcomes from the ACURATE neo AS study support the safety and performance of TAVI with the ACURATE neo2 valve.Graphic

Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma

Lenalidomide-dexamethasone (Rd) is standard treatment for elderly patients with multiple myeloma (MM). In this randomized phase 3 study, we investigated efficacy and feasibility of dose/schedule-adjusted Rd followed by maintenance at 10 mg per day without dexamethasone (Rd-R) vs continuous Rd in elderly, intermediate-fit newly diagnosed patients with MM. Primary end point was event-free survival (EFS), defined as progression/death from any cause, lenalidomide discontinuation, or hematologic grade 4 or nonhematologic grade 3 to 4 adverse event (AE). Of 199 evaluable patients, 101 received Rd-R and 98 continuous Rd. Median follow-up was 37 months. EFS was 10.4 vs 6.9 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.95; P = .02); median progression-free survival, 20.2 vs 18.3 months (HR, 0.78; 95% CI, 0.55-1.10; P = .16); and 3-year overall survival, 74% vs 63% (HR, 0.62; 95% CI, 0.37-1.03; P = .06) with Rd-R vs Rd, respectively. Rate of ≥1 nonhematologic grade ≥3 AE was 33% vs 43% (P = .14) in Rd-R vs Rd groups, with neutropenia (21% vs 18%), infections (10% vs 12%), and skin disorders (7% vs 3%) the most frequent; constitutional and central nervous system AEs mainly related to dexamethasone were more frequent with Rd. Lenalidomide was discontinued for AEs in 24% vs 30% and reduced in 45% vs 62% of patients receiving Rd-R vs Rd, respectively. In intermediate-fit patients, switching to reduced-dose lenalidomide maintenance without dexamethasone after 9 Rd cycles was feasible, with similar outcomes to standard continuous Rd. This trial was registered at www.clinicaltrials.gov as #NCT02215980.

A retrospective study of amrubicin monotherapy for the treatment of relapsed small cell lung cancer in elderly patients

PurposeAmrubicin is one of the most active chemotherapeutic drugs for small cell lung cancer (SCLC). Previous studies reported its effectiveness and severe hematological toxicity. However, the efficacy of amrubicin monotherapy in elderly patients with SCLC has not been described. The objective of this study was to investigate the feasibility of amrubicin monotherapy in elderly patients and its efficacy for relapsed SCLC.MethodsA retrospective cohort study design was used. We retrospectively evaluated the clinical effects and adverse events of amrubicin treatment in elderly (≥70 years) SCLC patients with relapsed SCLC.ResultsBetween November 2003 and September 2015, 86 patients (aged ≥70 years) received amrubicin monotherapy for relapsed SCLC at four institutions. There were 42 cases of sensitive relapse (S) and 44 of refractory relapse (R). S cases with median age of 75 years (range 70–85 years) and R cases with median age of 74 years (range 70–84 years) were included in our analysis. The median number of treatment cycles was three (range 1–9), and the response rate was 33.7% (40.5% in the S and 27.2% in the R cases). Median progression-free survival time was 4.0 months in the S and 2.7 months in the R patients (p = 0.013). Median survival time from the start of amrubicin therapy was 7.6 months in the S and 5.5 months in the R cases (p = 0.26). The frequencies of grade ≥3 hematological toxicities were as follows: leukopenia, 60.4%; neutropenia, 74.4%; anemia, 11.6%; thrombocytopenia, 16.2%; and febrile neutropenia, 17.4%. Treatment-related death was observed in one patient.ConclusionAlthough hematological toxicities, particularly neutropenia, were severe, amrubicin showed favorable efficacy, not only in the S but also in the R cases, as shown in previous studies. Amrubicin could be a preferable standard treatment in elderly patients with relapsed SCLC. These results warrant further evaluation of amrubicin in elderly patients with relapsed SCLC by a prospective trial.

First-line gefitinib treatment in elderly patients (aged ≥75 years) with non-small cell lung cancer harboring EGFR mutations.

The efficacy of gefitinib [an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor] in elderly patients with non-small cell lung cancer (NSCLC) and EGFR mutation has not been elucidated. Therefore, the objective of this study was to investigate the efficacy and feasibility of gefitinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations. We retrospectively evaluated the clinical effects of gefitinib as a first-line treatment for elderly (≥75 years) NSCLC patients with EGFR mutations (exon 19 deletion or exon 21 L858R mutation). All patients were initially treated with gefitinib (250 mg/day) at seven institutions. Between January 2006 and December 2012, 62 patients (17 men, 45 women) with a median age of 80 years (range, 75-89 years) were included in our analysis. The overall response and disease control rates were 61.2 and 83.8 %, respectively, and the median progression-free survival and overall survival were 13.2 and 19.0 months, respectively. Common adverse events included rash, diarrhea, and liver dysfunction. Major grade 3 or 4 toxicities included skin rash (3.2 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (21.0 %). Gefitinib treatment was discontinued owing to adverse events of liver dysfunction in 3 patients, drug-induced pneumonitis in 2, and diarrhea in 1. First-line gefitinib could be a preferable standard treatment in elderly patients with advanced NSCLC harboring sensitive EGFR mutations.

Phase II study of topotecan and cisplatin with sequential radiotherapy in elderly small cell lung cancer patients (Okayama Lung Cancer Study Group; OLCSG 0102).

7572 Background: The standard treatment for elderly patients with localized small cell lung cancer (LD-SCLC) has not been established. The Okayama Lung Cancer Study Group previously performed a pha...

Phase II trial of carboplatin and pemetrexed combination in elderly patients with advanced non-squamous non small cell lung cáncer (NS-NSCLC). A Galician Lung Cancer Group Study.

e19017 Background: The standard treatment for elderly patients in advanced NS-NSCLC is not defined. The aim of this study was to evaluate the efficacy and safety profile of the combination of carbo...

Safety and Efficacy of Dose Attentuated R-CHOP Chemotherapy for Treatment of Diffuse Large B Cell Lymphoma in the Very Elderly: A Cohort Study

Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and is frequently diagnosed in elderly patients. Elderly patients with DLBCL are known to have worse outcomes than younger patients with the same disease, in part due to comorbidities and poor performance status that may decrease their ability to tolerate treatment. A recent phase II study (Lancet Oncology 2011;12:460-8) demonstrated that patients with DLBCL who were older than 80 years of age had excellent tolerability while still maintaining efficacy when treated with an attenuated dose of R-CHOP called “R-mini-CHOP”. This paper prompted a change in treatment policy of very elderly patients with DLBCL at the London Regional Cancer Program. In November 2011, we began treating all DLBCL patients > 80 (and select patients aged 70-79 with significant comorbidities) with the R-mini-CHOP regimen rather than with standard R-CHOP or a ‘randomly dose-attenuated version’ of R-CHOP, which had been our practice prior to the policy change.Objective: This quality assurance study was undertaken in order to monitor and ensure the safety and efficacy of this practice change.Methods: Data was collected prospectively on all elderly patients with DLBCL who were initiated on R-mini-CHOP between November 2011 and January 2013. A retrospective chart review was also performed on patients > 80 treated at our centre in the preceding 10 years, after R-CHOP became standard treatment in elderly patients with DLBCL. We used 16 patients > 80 who received full dose R-CHOP between January 2010 and November 2011 as a historical control group for our prospective cohort.Results: Since November 2011, 17 patients (median age 81, range 71-90) have been treated with R-mini-CHOP and were enrolled in this quality assurance study. All 17 patients had stage III or IV disease. In contrast, only 6/16 patients in the retrospective group were advanced stage (p=0.00004). 12/17 R-mini-CHOP patients (70.6%) had an ECOG > 1, vs. 7/16 R-CHOP patients (43.8%, p=0.070). No dose modifications have been required in patients on R-mini-CHOP. 11/16 patients on R-CHOP underwent dose reductions due to side effects of chemotherapy. The majority of patients in both cohorts received primary prophylaxis with neupogen/neulasta. Five patients remain on R-mini-CHOP, all showing evidence of clinical response. Follow-up is too short to report on PFS or OS, but overall response rate thus far is 10/12 (83%) with 7 CRs (58.3%) and 3 PRs (25%). This compares favorably to the retrospective group who had an ORR of 13/16 (81%, p=0.30), 7 CRs (43.8%) and 6 PR’s (37.5%). One patient in each group had stable disease at the end of treatment. One mini-R-CHOP patient progressed on treatment and ultimately died of lymphoma. In the retrospective cohort, 4 deaths occurred secondary to infectious complications of chemotherapy during treatment period.C onclusions: Results with R-mini-CHOP have been encouraging so far. Despite the more aggressive disease (higher stage, inferior ECOG) in our R-mini-CHOP patients compared to the historical controls treated with R-CHOP, similar response rates are being achieved, with fewer adverse effects and better tolerability. Ongoing enrollment and longer follow-up will further help define the role of R-mini-CHOP in the very elderly patient population.Updated results with longer followup will be presented at the meeting. DisclosuresNo relevant conflicts of interest to declare.

A Randomized Phase III Multicenter Trial of Customized Chemotherapy Versus Standard of Care for 1St Line Treatment of Elderly Patients with Advanced Non-Small-Cell Lung Cancer (Nsclc): the Elderly Patient Individualized Chemotherapy (Epic) Trial

ABSTRACT Background: Phase III trial aiming to compare first line pharmacogenomic-driven chemotherapy based on Excision-Repair-Cross-Complementing-1 (ERCC1, E), Ribonucleotide Reductase subunit M1 (RRM1, R) and Thymidylate Synthase (TS, T) gene expression versus standard treatment in elderly patients (pts) with advanced NSCLC. Trial design: pts aged ≥70 years, ECOG Performance Status 0 or 1, EGFR negative mutational status, chemonaive stage IV NSCLC will be evaluated. Pts will be randomized (2:1) to experimental arm (A) or standard arm (B). In arm A, treatment will be based on histology, E, R and T mRNA expression. The cut-off for high or low expression have been previously defined. Treatments for pts with squamous NSCLC: carboplatin for E low/R high, gemcitabine for E high/R low, carboplatin and gemcitabine for E low/R low, docetaxel or vinorelbine for E high/R high. Treatments for non-squamous NSCLC pts: carboplatin for E low/T high, pemetrexed for E high/T low, carboplatin and pemetrexed for E low/T low, gemcitabine for E high/T high/R low, docetaxel or vinorelbine for E high/T high/R high. In arm B treatment will be at the investigator discretion. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, response rate (RECIST 1.1) and tolerability (CTCAE version 4.0). Feasibility of treatment selection based on pharmacogenomic parameters will be also assessed. Treatment will continue to a maximum of 6 cycles if tolerated or until disease progression. Assuming an exponential survival distribution for both arms and a median survival time of 8 months in the control arm, we anticipate to detect an improvement of 3 months in the median survival time in the experimental arm. To have 90% power to detect a three-month improvement in median survival at a significance level of 5% (2-sided) and assuming a 10% failure rate in gene analyses or loss to follow-up rate, a sample size of 567 patients is planned. Conclusion: To our knowledge, this is the first prospective pharmacogenomic-driven trial designed in elderly advanced NSCLC population. Disclosure: D. Cortinovis: Consultant for AZ, BI, Roche and Lilly; M. Papotti: Honoraria have been received from Eli Lilly; G. Scagliotti: Honoraria have been received from Eli Lilly, Roche, Pfizer and Astrazeneca. All other authors have declared no conflicts of interest.

A phase II study of S-1 chemotherapy with concurrent thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer: The Okayama Lung Cancer Study Group Trial 0801

BackgroundAlthough thoracic irradiation (TRT) is a standard treatment for elderly patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treatment outcomes are poor. We previously reported a phase I trial combining S-1, an oral 5-fluorouracil derivative, and thoracic radiation, which yielded safe and effective outcomes. MethodsIn this phase II trial, 30 patients aged 76years or older with LA-NSCLC received S-1 (80mg/m2 on days 1–14 and 29–42) and TRT (60Gy). The primary end-point was the response rate. ResultsThe median age and pre-treatment Charlson score were 79years and 1, respectively. The mean proportions of the actual doses of S-1 and TRT delivered relative to the planned doses were 95% and 98%, respectively. Partial responses were observed in 19 patients (63%; 95% confidence interval: 45–82%), which did not attain the end-point. At a median follow-up time of 23.7months, the median progression-free survival and median survival times were 13.0months and 27.9months, respectively. No difference in efficacy was observed upon stratification by tumour histology. Toxicities were generally mild, except for grade 3 or greater febrile neutropenia and pneumonitis in 7% and 10% of patients, respectively. No patient developed severe oesophagitis. ConclusionsAlthough the primary end-point was not met, concurrent S-1 chemotherapy and radiotherapy yielded favourable survival data. Also, the combined treatment was well-tolerated in elderly patients with LA-NSCLC.

Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptor-mutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group Study

The clinical efficacy and outcomes of gefitinib therapy as a first-line treatment for elderly patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations were analyzed retrospectively. We analyzed chemotherapy-naïve NSCLC patients aged 75 years or older who had EGFR mutations (exon 19 deletion mutation or L858R), who were initially treated with gefitinib (250 mg) once daily in Nagano Prefecture. A total of 55 patients (16 men, 39 women) with a median age of 81.1 years (range; 75-94 years) treated between April 2007 and July 2012 were analyzed. The overall response rate and disease control rate were 72.7 % (95 % confidence interval (CI); 59.5-82.9 %) and 92.7 % (95 % CI; 82.0-97.6 %), respectively. Median progression-free survival and overall survival from the start of gefitinib treatment were 13.8 months (95 % CI; 9.9-18.8 months) and 29.1 months (95 % CI; 22.4 months-not reached), respectively. Two-year survival rate was 59.5 % (95 % CI; 41.0-78.0 %). Major grade 3 toxicities were skin rash (1.8 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (7.3 %). First-line treatment with gefitinib for elderly EGFR-mutated NSCLC patients was effective and well tolerated. The results suggest that first-line gefitinib should be considered as a preferable standard treatment in elderly patients with advanced NSCLC harboring EGFR mutations.

Feasibility of Definitive Concurrent Chemoradiation Therapy for Patients Over 80 Years Old With Non-small Cell Lung Cancer

Radiation therapy alone is the standard treatment for elderly patients with locally advanced non-small-cell lung cancer (NSCLC). However curative thoracic radiation therapy with concurrent chemotherapy may be feasible to selected elderly patients with NSCLC. This retrospective study was aimed to evaluate the safety and tolerability of concurrent chemoradiation therapy (CCRT) in patients aged 80 years or older.

1220 - Doublet versus SINGLE Cytotoxic Agent as First-Line Treatment for Elderly Patients with Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

ABSTRACT The standard treatment for elderly patients with advanced non-small cell lung cancer (NSCLC) is still debated. As a result, we performed a meta-analysis of all randomized controlled trials comparing the efficacy of doublet versus single third-generation cytotoxic agent in the elderly patients with advanced NSCLC. Finally, eight eligible trials involved 2108 patients were identified. The intention to treatment (ITT) analysis demonstrated that doublet therapy significantly improved OS (HR0.85 95%CI 0.72-1.00, p = 0.048), PFS (HR 0.72, 95%CI 0.55-0.93, p = 0.012), 1-year SR (RR 1.18, 95%CI 1.02-1.36, p = 0.027) and ORR (RR1.65,95%CI 1.36-1.99, p = 0.000), compared with single cytotoxic agent. Sub-group analysis also favored platinum-based doublet therapy in terms of OS, PFS/TTP, 1-year SR and ORR. Though gemcitabine-based doublet significantly increased ORR compared with single agent (RR1.51, 95%CI 1.21-1.87, p = 0.000), it did not translate into increase in survival benefits in terms of OS, PFS and 1-year SR. More incidences of grade 3 or 4 hematologic toxicities were observed in doublet therapy group. With respect to grade 3 or 4 non-hematologic toxicities, equivalent frequencies were found between groups excluding more incidence of neutrotoxicity in doublet therapy group. Our data indicated that doublet therapy was superior to single third-generation cytotoxic agent for elder patients with advanced NSCLC. The optimal drug dosage and treatment schedule of platinum-based doublet should be investigated in future prospective clinical trials. Gemcitabine-based doublet could be considered for elderly patients who were not suitable for platinum-based chemotherapy. Disclosure All authors have declared no conflicts of interest.

Toxicity in patients receiving adjuvant docetaxel + hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer: a preplanned safety report of the SPCG-13 trial

Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). The inclusion criteria are the following: men >18 and ≤75 years of age, WHO/ECOG performance status 0--1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4+3), PSA >10; T2, Gleason 8--10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mgm(-2) d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3--4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3--4 toxicities at 12 weeks after the randomization. Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.

Concurrent chemoradiotherapy for elderly patients with stage III non-small cell lung cancer

PurposeCombined chemoradiotherapy is standard management for locally advanced non-small cell lung cancer (LA-NSCLC), but standard treatment for elderly patients with LA-NSCLC has not been confirmed yet. We evaluated the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for elderly patients with LA-NSCLC.Materials and MethodsAmong patients older than 65 years with LA-NSCLC, 36 patients, who underwent CCRT were retrospectively analyzed. Chemotherapy was administered 3-5 times with 4 weeks interval during radiotherapy. Thoracic radiotherapy was delivered to the primary mass and regional lymph nodes. Total dose of 54-59.4 Gy (median, 59.4 Gy) in daily 1.8 Gy fractions and 5 fractions per week.ResultsRegarding the response to treatment, complete response, partial response, and no response were shown in 16.7%, 66.7%, and 13.9%, respectively. The 1- and 2-year overall survival (OS) rates were 58.2% and 31.2%, respectively, and the median survival was 15 months. The 1- and 2-year progression-free survivals (PFS) were 41.2% and 19.5%, respectively, and the median PFS was 10 months. Regarding to the toxicity developed after CCRT, pneumonitis and esophagitis with grade 3 or higher were observed in 13.9% (5 patients) and 11.1% (4 patients), respectively. Treatment-related death was not observed.ConclusionThe treatment-related toxicity as esophagitis and pneumonitis were noticeably lower when was compared with the previously reported results, and the survival rate was higher than radiotherapy alone. The results indicate that CCRT is an effective in terms of survival and treatment related toxicity for elderly patients over 65 years old with LA-NSCLC.

An Overview of the VISTA Trial: Newly Diagnosed, Untreated Patients with Multiple Myeloma Ineligible for Stem Cell Transplantation

Multiple myeloma, a plasma cell neoplasm, is the second most common hematologic malignancy after non-Hodgkins lymphoma and is responsible for 2% of cancer deaths. Melphalan and prednisone (MP) has been the standard treatment in elderly patients for many decades. The VISTA study evaluated the effect of this combination with or without the first-in-class proteasome inhibitor bortezomib in newly diagnosed myeloma patients who were not candidates for autologous stem cell transplantation. Altogether 682 patients were enrolled and prospectively randomized in this trial. All patients received nine 6-week cycles of oral melphalan (9 mg/m(2)) and prednisone (60 mg/m(2)) on days 1-4, either alone or with bortezomib administered intravenously (1.3 mg/m(2) on days 1, 4, 8, 11, 22, 25, 29 and 32 during the first four cycles and on days 1, 8, 22, 29 during remaining course of therapy). Median time to progression (the primary end point of the trial) was 24 months in the bortezomib-containing group compared with 16.6 months in the control group (p < 0.001). Response was evaluated in 337 patients receiving bortezomib compared with 331 patients in the control group who received MP alone; the percentages of partial response or better was 71 vs 35% (p < 0.001), with complete response seen in 30 vs 4%, respectively (p < 0.001). Median response duration in both groups was 19.9 versus 13.1 months, respectively. Median overall survival has not been reached in VMP group compared with 43 months in the MP group (p < 0.001), and this benefit is maintained after long term follow-up and subsequent antimyeloma therapies. Hematological adverse events (AEs) were similar in both groups, although patients in the bortezomib group experienced more frequent peripheral sensory neuropathy (including 13% grade 3, with less than 1% grade 4). Overall, the occurrence of grade 3 AEs was higher in patients receiving bortezomib (53 vs 44%, p = 0.02), but the risk of grade 4 AEs was identical (28 vs 27%). These results confirm the superiority of MP plus bortezomib combination over MP therapy in treatment-naive patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation.

Effect of thalidomide with melphalan and prednisone on health-related quality of life (HRQoL) in elderly patients with newly diagnosed multiple myeloma: a prospective analysis in a randomized trial

Thalidomide with melphalan/prednisone (MPT) was defined as standard treatment in elderly patients with multiple myeloma (MM) based on five randomized trials. In one of these trials, HOVON49, a prospective health-related quality-of-life (HRQoL) study was initiated in order to assess the impact of thalidomide on QoL. Patients aged >65 years with newly diagnosed MM were randomized to receive melphalan plus prednisone (MP) or MPT, followed by thalidomide maintenance in the MPT arm. Two hundred eighty-four patients were included in this side study (MP, n=149; MPT n=135). HRQoL was assessed with the EORTC Core QoL Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24) at baseline and at predetermined intervals during treatment. The QLQ-C30 subscales physical function (P=0.044) and constipation (P<0.001) showed an improvement during induction in favour of the MP arm. During thalidomide maintenance, the scores for the QLQ-MY24 paraesthesia became significantly higher in the MPT arm (P<0.001). The QLQ-C30 subscales pain (P=0.12), insomnia (P=0.068), appetite loss (P=0.074) and the QLQ-MY24 item sick (P=0.086) scored marginally better during thalidomide maintenance. The overall QoL-scale QLQ-C30-HRQoL showed a significant time trend towards more favourable mean values during protocol treatment without differences between MP and MPT. For the QLQ-C30 subscales emotional function and future perspectives, difference in favour of the MPT arm from the start of treatment was observed (P=0.018 and P=0.045, respectively) with no significant 'time × arm' interaction, indicating a persistent better patient perspective with MPT treatment. This study shows that the higher frequency of toxicity associated with MPT does not translate into a negative effect on HRQoL and that MPT holds a better patient perspective.