Aflibercept and 5-FU vs. FOLFOX as 1st line treatment for older adults or frail elderly patients with metastatic colorectal cancer - The randomized phase 2 AIO / IKF ELDERLY trial (AIO-KRK-0117 / IKF 629).

The IFM2017-03 Phase 3 Trial: A Dexamethasone Sparing-Regimen with Daratumumab and Lenalidomide for Frail Patients with Newly-Diagnosed Multiple Myeloma

UK Fifth National Colorectal Cancer Consensus Meeting 2010

Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial

Geriatric Impairments and Low Muscle Mass Are Associated with Treatment Discontinuation and Overall Survival in Newly Diagnosed Non-Transplant Eligible Multiple Myeloma Patients (nte-NDMM) Treated with Dose-Adjusted Melphalan-Prednisone-Bortezomib (MPV) — Results of the Dutch HOVON 123 Study

Background: There is an unmet need for active treatments in elderly, non-FIT patients, with aggressive lymphomas, allowing to preserve patient's Quality of life (QoL). Moving forward to setting up a suitable schedule, we devised a metronomic chemotherapy (MTN-CHT) protocol, termed DEVEC, consisting of prednisolone (PDN), cyclophosphamide (CTX), etoposide (ETO), oral vinorelbine (VRN) ± rituximab(RTX). Since February 2011, this MTN-CHT schedule, was adopted in six clinical centres affiliated with the FIL. Candidate for this palliative schedule were aggressive B and T cell lymphoma patients, considered unfit for standard chemotherapies. Forty-two patients (31 DLBCL and 11 PTCL), with a median age of 79 years, were evaluated for outcome analysis. The schedule was well tolerated even in frail pts; hematologic toxicity was moderate and manageable with GF. The rate of extra-hematologic toxicity of grade ≥ 3 was 19%, mostly due to infections. Only 3/42 (7%) pts discontinued treatment because of toxicity or death. The overall response rate (ORR) was 64.3% including 23.8% CR, 4.7% unconfirmed CR (uCR) and 38% PR. The median overall survival (OS) and progression free survival (PFS) were 15 (95% CI = 8.645–21.355) and 10 (CI 95% = 5.520–14.480) months, respectively. On the basis of these results and giving the lack of MTN-CHT trials in lymphoma patients, the elderly commission of the FIL released in November 2016 the DEVEC trial (EUDRACT 2016-003703-62). Methods/Design: This is an open label, non-randomized, multicentre, phase II study, to evaluate the efficacy and safety of DEVEC oral schedule (fig1) in large B-cell (LBCL) and Burkitt lymphoma (BL) diagnosed in elderly unfit and frail patients who are R/R after previous treatment, and in super-frail patients at disease onset. Patients will be enrolled according to Bryant & Day two-stage optimal design.Co-Primary Objectives: 1) To explore the activity of the DEVEC induction + maintenance schedule; 2) To explore the safety of the DEVEC induction + maintenance schedule.Secondary Objectives: To evaluate the ORR (CR, Cru, PR) and the Clinical Benefit evaluated at the end of induction (EOI) cycles. OS, PFS, EFS, DFS, to assess QoL. Treatment Schedule: A) Induction phase: six courses (q 28 days) of PDN + ETO + VRN + CTX, ±RTX. Patients in PR and SD after 2 cycles will continue with additional 4 courses. At the end of the induction phase patients in ≥PR will continue treatment with B) Maintenance phase: six courses of PDN + VRN + CTX. (q28 days). Primary Endpoints: The primary efficacy endpoint is defined in terms of CRR (CR + Cru rate). The primary safety endpoint is defined as incidence, nature, and severity of adverse events. Keywords: Chemotherapy; diffuse large B-cell lymphoma (DLBCL); elderly.

Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

We conducted a phase II study to assess activity and safety profile of bendamustine and rituximab in elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) who were prospectively defined as frail using a simplified version of the Comprehensive Geriatric Assessment (CGA). Patients had to be over 70 years of age, with histologically confirmed DLBCL. Frail patients were those younger than 80 years with a frail profile at CGA or older than 80 years with an unfit profile. Treatment consisted of 4-6 courses of bendamustine [90 mg/m2 days (d)1-2] and rituximab (375 mg/m2 d1) administered every 28 days. Other main study end points were complete remission rate and the rate of extra-hematologic adverse events. Forty-nine patients were enrolled of whom 45 were confirmed eligible. Overall, 24 patients achieved a complete remission (53%; 95%CI: 38-68%) and the overall response rate was 62% (95%CI: 47-76%). The most frequent grade 3-4 adverse event was neutropenia (37.8%). Grade 3-4 extra-hematologic adverse events were observed in 7 patients (15.6%; 95%CI: 6.5-29.5%); the most frequent was grade 3 infection in 2 patients. With a median follow up of 33 months (range 1-52), the median progression-free survival was ten months (95%CI: 7-25). The study shows promising activity and manageable toxicity profile of BR combination as first-line therapy for patients with DLBCL who are prospectively defined as frail according to a simplified CGA, as adopted in this trial (clinicaltrials.gov identifier: 01990144).

Blood Transfusion and Overall Quality of Life After Hip Fracture in Frail Elderly Patients—The Transfusion Requirements in Frail Elderly Randomized Controlled Trial

BackgroundA previous Phase I/II study demonstrated that TAS‐102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer.MethodsThis is a multicenter, single‐arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression‐free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs).ResultsBetween 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70–88); the ECOG‐PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3–4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%).ConclusionsFTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross‐resistance with 5‐fluorouracil.Clinical trial registration: UMIN clinical trials registry (UMIN000025241).

ABSTRACTPurpose : To examine the relationship between ingestive skill performance while eating and drinking and frailty status in acutely-hospitalized elderly patients and to examine whether there is a relationship between the proportion of ingestive skill difficulties and Length of Hospital Stay (LOS) and discharge destination. Methods : Frail (n = 64) and robust (n = 40) acutely-hospitalized elderly patients were assessed using The McGill Ingestive Skills Assessment. Results : Forty-three ingestive skills were significantly more affected in frail patients (21.9% to 95.3%) versus robust patients (2.5% to 65.0%). When adjusting for frailty status, difficulties in self-feeding and texture management were related to prolonged LOS, and difficulties in positioning and liquid ingestion were related to discharge to institutional care. Conclusion : Ingestive skill difficulties among acutely-hospitalized frail elderly patients were frequent and characterized by great complexity. This necessitates a broad range of management strategies related to the patients’ ability in positioning, self-feeding skills, as well as oropharyngeal sensorimotor skills.

Ixazomib and Daratumumab without Dexamethasone (I-Dara) in Elderly Frail RRMM Patients. a Multicenter Phase 2 Study (IFM 2018-02) of the Intergroupe Francophone Du Myélome (IFM)

BackgroundHeart failure (HF) is associated with a high rate of readmissions within 30 days post-discharge and in the following year, especially in frail elderly patients. Biomarker data are scarce in this high-risk population. This study assessed the value of early post-discharge circulating levels of ST2, NT-proBNP, CA125, and hs-TnI for predicting 30-day and 1-year outcomes in comorbid frail elderly patients with HF with mainly preserved ejection fraction (HFpEF).MethodsBlood samples were obtained at the first visit shortly after discharge (4.9 ± 2 days). The primary endpoint was the composite of all-cause mortality or HF-related rehospitalization at 30 days and at 1 year. All-cause mortality alone at one year was also a major endpoint. HF-related rehospitalizations alone were secondary end-points.ResultsFrom February 2014 to November 2016, 522 consecutive patients attending the STOP-HF Clinic were included (57.1% women, age 82 ± 8.7 years, mean Barthel index 70 ± 25, mean Charlson comorbidity index 5.6 ± 2.2). The composite endpoint occurred in 8.6% patients at 30 days and in 38.5% at 1 year. In multivariable analysis, ST2 [hazard ratio (HR) 1.53; 95% CI 1.19–1.97; p = 0.001] was the only predictive biomarker at 30 days; at 1 year, both ST2 (HR 1.34; 95% CI 1.15–1.56; p < 0.001) and NT-proBNP (HR 1.19; 95% CI 1.02–1.40; p = 0.03) remained significant. The addition of ST2 and NT-proBNP into a clinical predictive model increased the AUC from 0.70 to 0.75 at 30 days (p = 0.02) and from 0.71 to 0.74 at 1 year (p < 0.05). For all-cause death at 1 year, ST2 (HR 1.50; 95% CI 1.26–1.80; p < 0.001), and CA125 (HR 1.41; 95% CI 1.21–1.63; p < 0.001) remained independent predictors in multivariable analysis. The addition of ST2 and CA125 into a clinical predictive model increased the AUC from 0.74 to 0.78 (p = 0.03). For HF-related hospitalizations, ST2 was the only predictive biomarker in multivariable analyses, both at 30 days and at 1 year.ConclusionsIn a comorbid frail elderly population with HFpEF, ST2 outperformed NT-proBNP for predicting the risk of all-cause mortality or HF-related rehospitalization. ST2, a surrogate marker of inflammation and fibrosis, may be a better predictive marker in high-risk HFpEF.

Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild-type unresectable colorectal cancer. It is especially effective for left-sided tumors; therefore, panitumumab as first-line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin-based or irinotecan-based combination regimens. First-line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy-naïve frail or elderly patients with unresectable RAS wild-type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first-line treatment. We conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities. Thirty-six patients (median age: 81 [range, 67-88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty-three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty-eight patients (77.8%) had left-sided CRC, whereas eight (22.2%) had right-sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4-67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5-87.7). The RR of patients with left- and right-sided tumors was 65.4% (95% CI, 44.3-82.8) and 0.0% (95% CI, 0.0-36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%). Panitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

BackgroundColorectal cancer is one of the tumors with the highest morbidity and mortality rates in China and the world. Regorafenib is a targeted drug for standard third-line treatment of metastatic colorectal cancer (mCRC). Regorafenib monotherapy has shown certain efficacy in the elderly population, but more robust evidence is needed. The aim of this study was to evaluate the dosing characteristics, prognosis, and safety of regorafenib monotherapy in elderly Chinese patients with mCRC.MethodsThis retrospective study comprised elderly patients (aged ≥60 years) with mCRC who received regorafenib monotherapy as a third-line or above treatment in 10 hospitals from August 2017 to June 2020. We analyzed the association between different dosing regimens and prognosis. The primary endpoint was overall survival (OS), and other endpoints included progression-free survival (PFS) and adverse events (AEs).ResultsIn total, 203 patients were included in the analysis. The median PFS was 3.88 months [95% confidence interval (CI): 3.48–5.65], and the median OS was 10.1 months (95% CI: 8.94–12.1). There was no significant difference in the survival curves between the different dosage groups. The multivariate Cox analysis showed a significant benefit in OS in the high final daily dose group (120–160 mg/day) [hazard ratio (HR): 0.45, 95% CI: 0.25–0.84, P=0.01], which was further confirmed by the propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis. No significant association was found between the initial daily dose and prognosis. Nor was any significant association found between PFS and drug dosage. Subsequently, an age subgroup analysis was conducted using 70 years as the cut-off value. In those aged <70 years, the application of higher final doses (120–160 mg/day) was significantly associated with the prolongation of OS compared to a final dose of 80 mg/day [HR (95% CI): 0.38 (0.16–0.91), P=0.03], and the prolongation of OS was predominantly observed in the 120 mg/day dose group [HR (95% CI): 0.24 (0.09–0.67), P=0.006]. Besides, we observed a statistically insignificant increase in the incidence of AEs in the higher dose group compared to the lower dose group.ConclusionsRegorafenib monotherapy was shown to be efficacious in the elderly population, but further evidence is needed for guidance. Based on our multicenter real-world investigation, the final daily dose was significantly associated with OS. For those aged <70 years, maintaining the final dose at 120 mg/day may have prognostic advantages. The suggested medication protocol requires validation through comprehensive clinical trials.