Summary Thalidomide is an effective agent for advanced refractory or relapsed multiple myeloma (MM), although dose‐limiting toxicity (DLT) may limit its use. This Phase I study found that a combination of low‐dose thalidomide with bendamustine and prednisolone (BPT) maintained or increased efficacy, whilst avoiding DLT in 28 patients with MM that was refractory or that had relapsed after conventional chemotherapy or high‐dose therapy with stem‐cell support. BPT comprised fixed doses of bendamustine (60 mg/m2) and prednisolone (100 mg), and escalating doses of thalidomide (50, 100, 200 mg). Treatment cycles were repeated every 28 d until the occurrence of maximum response, DLT, or disease progression. Twenty‐four patients responded after at least two cycles (four complete remission, six very good partial remission, 14 partial remission). Median progression‐free and overall survival for all patients was 11 and 19 months respectively. Only mild/moderate non‐haematological side effects were observed and no patient developed dose‐limiting haematotoxicity. Transient grade 3–4 neutropenia was reported in 12 patients, and grade 3–4 thrombocytopenia occurred in two patients. We conclude that BPT therapy was well tolerated in patients with relapsed or refractory MM, with a response rate higher than 80%. The maximum tolerated dose of thalidomide was not reached in this study.
Background The purpose of this study was to assess satisfaction and pain intensity in patients undergoing minor hand surgery under local anesthesia (LA) with or without sedation.
In our single-centre study of thoracic epidural analgesia, serious adverse events occurred in 0.1% cases (1 : 1000), whereas long-term outcome was compromised in 0.014% (1.4 : 10 000) which is similar to the serious adverse event rates and outcomes reported in the current literature.
This study used the National Survey of Ambulatory Surgery (NSAS) database to measure the incidence of and risk factors for symptoms in the ambulatory surgery center and problems within 24 h after isolated carpal tunnel release (CTR). The NSAS contained records on 400,000 adult patients with carpal tunnel syndrome who were treated with CTR in 2006, based on ICD-9 codes. The type of anesthesia used and factors associated with symptoms and problems were sought in bivariate and multivariable statistical analyses. The mean duration of the procedure was 16±8.8 min. Only 5 % were performed under local anesthesia without sedation, 45 % with IV sedation, 28 % regional anesthesia, and 19 % general anesthesia. Symptoms in the ambulatory surgery center or a problem within 24 h after discharge were recorded in 10 % of patients, all of them minor and transient, including difficulties with pain and its treatment. The strongest risk factors were male sex, age of 45 years and older, and participation of an anesthesiologist. Local anesthesia and regional anesthesia were associated with more perioperative symptoms and postoperative problems. Most CTR are performed with some sedation in the United States. CTR is a safe procedure: one in 10 patients will experience a minor issue in the perioperative or immediate postoperative period.
2016-12-23T18:49:38
Thalidomide is a remarkably active agent in patients with advanced relapsed or refractory multiple myeloma (MM), but with a significant co morbidity due to side-effects such as neuropathy. We investigated whether lower doses of thalidomide in combination with weekly doses of bendamustine and prednisolone might be a more effective regimen with fewer side-effects especially in relation to neurotoxicity. Clinical studies in patients with newly diagnosed and relapsed MM have shown that bendamustine is effective as single agent as well as in combination with prednisolone. In a phase III study, overall response rate for bendamustine and prednisone was 75% as first line therapy. The purpose of this phase I study was the assessment of toxicity of the combination bendamustine, prednisolone, and thalidomide (BPT) in patients with advanced MM. The treatment consisted of a fixed dose of bendamustine (60 mg/qm) i.v. days 1, 8, and 15 and prednisolone (100 mg) p.o. days 1, 8, 15, and 22. Thalidomide was given to patient cohorts at escalating doses, starting with 50 mg up to a maximum of 200 mg daily. Four patients were enrolled at each dose level. If one dose limiting toxicity (DLT) occurred, additional two patients would be enrolled at that dose level. Cycles were repeated every 28 days for a minimum of 2 and a maximum of 10 cycles until maximum response, DLT, or progressive disease. Fourteen patients (4 in the first thalidomide dose level with 50 mg, 4 in the second dose level with 100 mg, and 6 patients in the third dose level with 200 mg) were enrolled. Median age was 69 years (range 61 - 78). The number of prior treatment regimens was 2 or more in all patients. Six younger patients were included who had failed VAD-like induction therapy (n=5) or stem cell mobilization (n=1). Six patients had been refractory to the last treatment. Results: All patients completed 2 cycles of BPT (1 completed 7 cycles, 4 completed 6 cycles, 3 completed 5 cycles, 3 completed 4 cycles, 2 completed 3 cycles, and 1 completed 2 cycles). Response was assessed using EBMT criteria modified to include near complete remission (nCR) and very good partial remission (VGPR). After at least 2 cycles of chemotherapy, 12 of 14 patients responded with 2 CR, 2 VGPR, 7 PR, and 1 MR (ORR 85%). Two patients had a stable disease. No DLT was observed at any dose level. Most common side-effects were constipation (7 patients WHO grade 1; 6 patients WHO grade 2), somnolence (4 patients WHO grade 1), and peripheral neuropathy (2 patients WHO grade 1; 2 patients WHO grade 2). None of the 14 patients developed dose-limiting hematological toxicity as defined by an ANC < 1,0 x 109/l for > 7 days or an ANC < 0,5 x 109/l for > 3 days or platelet count < 25 x 109/l. Neutropenia was reported in 4 patients (WHO grade 4) but no thrombocytopenia was observed. No grade 3 or 4 non-hematological toxicity was encountered and no dose modification was required. BPT with daily thalidomide between 50 mg and 200 mg is well tolerated in patients with relapsed or refractory MM after conventional chemotherapy.
Thalidomide is an active single agent in advanced relapsed or refractory MM. Treatment, however, is associated with significant dose-dependent toxicity limiting his application. Combination of low dose thalidomide with bendamustine and prednisolone might be a way to maintain efficacy of the drug without dose limiting toxicity. The cytotoxic agent bendamustine combines a purine-like benzimidazol with a bifunctionally alkylating nitrogen mustard group. The drug is active in a variety of lymphoproliferative disorders with modest non-hematological and hematological toxicities. Previous clinical studies confirmed the efficacy of bendamustine monotherapy and in combination with prednisolone in patients with newly diagnosed and relapsed MM. In a phase III study of newly diagnosed patients, overall response rate for bendamustine and prednisone was 75% and shown to be superior to melphalan and prednisone in regard to progression free survival and quality of life. The purpose of this phase I study was to test the feasibility of the combination of BPT in advanced MM patients. The treatment consists of a fixed dose of bendamustine (60 mg/qm) i.v. day 1, 8, and 15 and prednisolone (100 mg) p.o. day 1, 8, 15, and 22. At the same time, thalidomide will be given orally in 4 patients cohorts with escalating doses, starting at 50 mg to a maximum of 200 mg daily. Cycles will be repeated every 28 days for a minimum of 2 and a maximum of 10 cycles until appearance of significant treatment-related toxicity or disease progression. Till now, four patients with stage IIIa MM were enrolled in the first dose level with 50 mg thalidomide daily. All patients had two prior treatment lines and three were refractory. Median age was 67 years (range 64 – 69 years). Results: All four patients completed at least 2 cycles of BPT-treatment (2 completed 6 cycles, 1 completed 3 cycles and 1 completed 2 cycles) and were evaluable for toxicity and efficacy. All patients responded after the first two cycles of therapy in three of them with decrease of the myeloma protein of more than 90%. One showed a reduction of the myeloma protein of 30%. Although median follow up is still short, no progression of disease was observed yet. Thalidomide in a dose of 50 mg daily given during 4.5 months median (range 2–6 months) was well tolerated. Most common site effects were constipation (three patients WHO grade 2) and somnolence (two patients WHO grade 1). None of the four patients developed dose-limiting hematotoxicity as defined by an ANC < 1,0 x 109/l for >7 days or an ANC < 0,5 x 109/l for > 3 days or platelet count < 25 x 109/l. Neutropenia was reported in 1 patient (WHO grade 2) but no thrombocytopenia was observed. No grade 3 or 4 non-hematological toxicity was encountered and no dose modification was required. BPT with a dose of 50 mg thalidomide daily is well tolerated in patients with relapsed or refractory MM. The next cohort of patients is currently treated with Thalidomide 100 mg daily to evaluate the maximal tolerable doses of the BPT regimen.
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