Combination Therapy of Bortezomib with Low-Dose Bendamustine in Elderly Patients with Advanced Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5122-5122 ◽  
Author(s):  
Irena Hrusovsky ◽  
Hans-Heinrich Heidtmann
Keyword(s):  
Multiple Myeloma ◽  
Combination Therapy ◽  
Elderly Patients ◽  
Low Dose ◽  
Alkylating Agents ◽  
High Rate ◽  
Treatment Modalities ◽  
Cross Resistance ◽  
High Dose ◽  
Indolent Lymphoma

Abstract Bortezomib has been approved for recurrent or therapy-resistent multiple myeloma in 2003. There is growing evidence that combination therapy of bortezomib with other agents considerably improves results (Richardson P, ASH 2004). Bendamustine is an alkylating agent widely used in Germany for treatment of multiple myeloma and indolent lymphoma. There is no cross-resistance to other alkylating agents. Weekly low dose application is well tolerated and highly effective in elderly patients with pretreated indolent lymphoma (Bremer K, ASCO 2003, Abstract 2410). Treatment modalities: We treated 17 pts (8 female, 9 male, median age 70 yrs (range 51–82) with relapsed multiple myeloma. Previous therapies ranged from 2 to 7 (median 4), and included 15 x thalidomide, 2 x tandem high dose melphalan, 2 x bortezomib/dexamethasone. Therapy regimen: bortezomib 1 – 1.3 mg/m2 d 1,4,8,11; bendamustine 60 mg/m2 d 1+8, dexamethasone 3x8 mg orally d 1–3 and d 8–10: ondansetrone 8 mg intravenously d 1,4,8,11. Cycles were repeated q3w until best response. The median number of cycles applied was 4 (range 3 – 6). Results: Outcome was evaluated according to SWOG criteria. ORR: 88%; CR (neg. immunofixation): 12% (n=2); PR 58% (n=10); MR 18% (n= 3); NC 12% (n=2). Median remission duration was 6+ months (range 3–12+ months). Until today, we observed 4 recurrences after 3 – 8 months. Toxicity comprised mild fatigue and thrombopenia. Lowest platelet count was 55/pL without bleeding, spontaneously reversible within 1 week. Three cases of neuropathia occurred, with controllable symptoms, in patients pretreated with thalidomide or bortezomib mono. Conclusion: Combination therapy of bortezomib with low dose bendamustine is well tolerated, induces a high rate of responses in spite of unfavourable patient characteristics, leads to early responses and can be limited to 3 months (i.e., 4 cycles), and can be done in an outpatient setting. Thus, bendamustine is a very promising agent to enhance bortezomib action, which warrants further study.

scholarly journals Three Drug Regimens for Newly Diagnosed Multiple Myeloma Transplant-Ineligible Elderly Patients - a Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5574-5574
Author(s):  
Abdul Aziz Siddiqui ◽  
Kazi Najamus-saqib Khan ◽  
Arafat Ali Farooqui ◽  
Muhammad Saad Farooqi ◽  
Muhammad Junaid Tariq ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Trial ◽  
Alkylating Agents ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Great Efficacy ◽  
Drug Regimens

Introduction: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT) tend to have comorbidities and/or advanced age that make this subset of patients difficult to manage with current drug regimens. Methods: A comprehensive literature search of PubMed, Embase, Clinicaltrials.gov and Web of Science was performed from inception and completed on 07/17/2019. Studies focusing on efficacy and tolerability of 3-drug regimens in patients with NDMM were included for the review. Results: Out of 3579 studies, a total of 10 (08 phase II and 03 phase III) clinical trials in last ten years (2010-2019) using 3-drug regimens in NDMM elderly pts (893M/807F) ineligible for ASCT (determined by investigators) were selected. A total of 1703/1740 NDMM pts were evaluated. Proteasome inhibitors (PIs) such as carfilzomib (C), bortezomib (V) and ixazomib (I) showed promising results in elderly transplant-ineligible NDMM pts. CLARION trial (phase III, n=955) compared two PIs (C and V) with melphalan (M) and prednisone. There was no statistically significant difference in progression-free survival (PFS) between two groups (median: 22.3 vs 22.1 months; HR: 0.91; 95% CI, 0.75-1.10, p = 0.159) as well as overall survival (OS) (HR: 1.08; 95% CI: 0.82-1.43). Difference in the least square means of the HR-QoL (Health related- quality of life) was 4.99 (p<.0001) favoring C-group. M may not be an ideal drug to combine with carfilzomib in this setting given more AEs.(Facon et al 2019). V as 3-drug regimen in combination with lenalidomide (L) in 242 pts achieved statistically significant prolonged PFS (median 43 mo) and OS (median 75 mo) with great efficacy and acceptable risk-benefit profile. (Durie et al 2017; phase III). Multinational phase II trial (n=70) by Dimopoulos et al (2019) evaluated I, with different fixed doses of cyclophosphamide (Cy). Median duration was 19 cycles, indicating the long-term tolerability of regimen. With favorable toxicity profile and maintained QoL scores, trial concluded that this therapy is tolerable in elderly transplant-ineligible NDMM pts. Tuchman et al (2017) in phase II trial (n=14) investigated (V-Cy-d) and achieved ORR of 64%, with ≥VGPR of 57%. Low dose V showed great efficacy with M yielding ORR of 86% and VGPR or better of 49% in phase II trial (n=101) that also evaluated Cy as 3-drug combination but results were more productive with M with longer PFS and OS which reduced when impact of frailty was examined on outcomes. Since toxicity was higher with M, trial suggested that 2-drug combination should be preferred in elderly frail patients. (Larocca et al 2015). Efficacy was quite promising when Bringhen et al (2014) trialed C with Cy-d; 87% OS and 76% PFS at 1 y in phase II trial (n=58) with much favorable safety profile. Monoclonal antibodies (mAb) such as elotuzumab (E) and pembrolizumab (Pe) are also tested in elderly. First study conducted on NDMM pts using humanized mAb; E, in phase II trial (n=40) by Takezako et al (2017) attained primary endpoint of the study (ORR) of (88%) and VGPR or better of 45% in Japanese pts with tolerable toxicities in elderly. No subjects on this study experienced severe peripheral neuropathy. KEYNOTE-185; a phase III multinational trial by Usmani et al (2019) evaluated Pe with Ld in 151 pts. FDA halted this study due to unfavorable benefit-risk profile; 19 deaths, 6 due to disease progression (PD), and 13 due to treatment-related AEs. Median PFS and median OS were not reached in either group. Immunomodulators such as L achieved one of the longest PFS reported in a trial of transplant ineligible patients (35 mo) by using LVd regimen in phase II multicenter trial (n=50). (O'Donnell et al 2018) Alkylating agents like bendamustine (ben) and M have been tested in different novel regimens. Decreasing intensity and increasing duration of ben resulted in better outcomes in phase II trial (n=59) by Berdeja et al (2016) and can be given as first line treatment. Ben yielded great results with low dose dexa as compared to high dose achieving 92% ORR. Original regimen was effective but relatively more toxic. Incidence of herpes and neuropathy decreased dramatically with the treatment modifications. Conclusion: Three-drug regimens having PIs, mABs, immunomodulators and alkylating agents have shown desirable results in NDMM transplant (ASCT)-ineligible elderly patients and are likely the emerging standard of care for NDMM. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Effect of Different Doses of Propofol and Nerve block Combined with General Anesthesia on The Intraoperative Anesthesia and Postoperative Awakening and Cognitive Function in Elderly Patients with Knee Osteoarthritis

2021 ◽  
Vol 7 (4) ◽  
pp. 697-705
Author(s):  
Jianhui Ma ◽  
Meimei Pang ◽  
Xin Ding ◽  
Shirong Fang ◽  
Lichao Chu
Keyword(s):  
Cognitive Function ◽  
Elderly Patients ◽  
General Anesthesia ◽  
Nerve Block ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Knee Oa ◽  
Different Doses

Objective. To explore the effect of different doses of propofol and nerve block combined with general anesthesia on the intraoperative anesthesia and postoperative awakening and cognitive function in elder patients with knee osteoarthritis (OA). Methods. According to the inclusion criteria for research object, we selected 98 elderly patients with knee OA who needed surgery and were admitted to our hospital from January 2019 to January 2021 for the study. Patients were divided into the low dose group (given 2 mg/kg propofol by pumping under constant speed during surgery) and the high dose group (given 4 mg/kg propofol by pumping during surgery) by the number table method to compare their indicators including the intraoperative anesthesia effect, with 49 cases in each group. Results. No between-group difference was shown in the anesthesia time and postoperative VAS scores, but the awakening time of the low dose group was significantly shorter than that of the high dose group (P<0.05); the differences in heart rate (HR) values at various time points between the two groups were not obvious, but the high dose group obtained significantly higher HR values at T4 than the low dose group; the mean arterial pressure (MAP) values of both groups were significantly reduced at Ti and then returned to the level before anesthesia (P>0.05); the bispectral index scores (BIS) of both groups experienced a marked drop at Ti and then recovered gradually, but failed to return to the level at T0 till the end, and a between-group difference in BIS indexes presented at Ti; the plasma corticosterone (CORT) concentration at Ti of both groups were significantly lowered and then returned to the level at T0, with no between-group difference; and compared with the low dose group, the high dose group achieved slightly lower mini-mental state examination (MMSE) scores at 24-72 h after surgery, with no significant difference between them (P>0.05). Conclusion. The therapy of different doses of propofol and nerve block combined with general anesthesia has no significant effect on the cognitive function in elderly knee OA patients after surgery. With the nerve block improving the analgesic effect, a low dose of propofol is good for the postoperative awakening of patients. Different doses of propofol inhibited the stress response to a different degree and produced good anesthesia outcomes in elderly patients, but comparatively speaking, a low-dose propofol ensures more smooth indexes and less effect on the intraoperative hemodynamics.

scholarly journals Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 8 (1) ◽  
pp. 45 ◽  
Author(s):  
Tamara Y. Milder ◽  
Sophie L. Stocker ◽  
Christina Abdel Shaheed ◽  
Lucy McGrath-Cadell ◽  
Dorit Samocha-Bonet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Low Dose ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Cochrane Library ◽  
High Dose ◽  
Dose Combination ◽  
Inhibitor Combination

Background: Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. Aims: To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. Methods: PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24–26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. Results: In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); −0.55% (−0.67, −0.43)) and weight (−2.00 kg (−2.34, −1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (−0.59% (−0.72, −0.46)) and weight (−0.57 kg (−0.89, −0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; −0.47 kg (−0.88, −0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. Conclusions: Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.

scholarly journals P2.17-10 Daily Low–Dose Cisplatin and High Dose Radiotherapy for Elderly Patients with Stage III NSCLC is Well Tolerated.

2018 ◽  
Vol 13 (10) ◽  
pp. S855-S856
Author(s):  
E.m.t. Dieleman ◽  
R. Van Os ◽  
W. Kolff ◽  
C.c.e. Koning ◽  
J.t. Annema ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Low Dose ◽  
Stage Iii ◽  
High Dose ◽  
Stage Iii Nsclc

scholarly journals Efficacy of Combination Therapy with Glycyrrhizinate, Antiallergic Agent, and Low Dose Steroid for Lenalidomide-induced Skin Eruptions in a Patient with Refractory Multiple Myeloma

2012 ◽  
Vol 61 (3) ◽  
pp. 89-92
Author(s):  
Masafumi MATSUGUMA ◽  
Toru TAKAHASHI ◽  
Hiroyuki NAKAMURA ◽  
Sumie HIRAMATSU ◽  
Takashi YAMAGUCHI ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Combination Therapy ◽  
Low Dose ◽  
Refractory Multiple Myeloma ◽  
Antiallergic Agent

Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome

2012 ◽  
Vol 88 (3) ◽  
pp. 249-259 ◽  
Author(s):  
Ibrahim Yakoub-Agha ◽  
Jean-Yves Mary ◽  
Cyrille Hulin ◽  
Chantal Doyen ◽  
Gérald Marit ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Low Dose ◽  
Prospective Trial ◽  
High Dose
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