反应停联合地塞米松治疗多发性骨髓瘤临床疗效分析

目的：探讨应用反应停联合地塞米松治疗多发性骨髓瘤的临床效果及其安全性。方法：2003年1月至2006年1月间我院住院患者40例,随机分为观察组和对照组。对照组单用反应停,观察组加用地塞米松。结果：反应停联合地塞米松组,总有效率85%,显著高于对照组的55%。观察组治疗前后的血常规、血沉、血钙、血清M蛋白等指标的变化更加显著。同时出现轻微的不良反应。结论：反应停联合地塞米松治疗多发性骨髓瘤,有很好的疗效,毒副反应轻微,患者可耐受,值得临床推广应用。     

反应停联合地塞米松治疗多发性骨髓瘤临床疗效分析

目的:探讨应用反应停联合地塞米松治疗多发性骨髓瘤的临床效果及其安全性.方法:2003年1月至2006年1月间我院住院患者40例,随机分为观察组和对照组.对照组单用反应停,观察组加用地塞米松.结果:反应停联合地塞米松组,总有效率85%,显著高于对照组的55%.观察组治疗前后的血常规、血沉、血钙、血清M蛋白等指标的变化更加显著.同时出现轻微的不良反应.结论:反应停联合地塞米松治疗多发性骨髓瘤,有很好的疗效,毒副反应轻微,患者可耐受,值得临床推广应用.     

Daratumumab,Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Chinese Patients with Relapsed or Refractory Multiple Myeloma: Phase 3 LEPUS (MMY3009) Study

BackgroundDaratumumab plus bortezomib/dexamethasone (D-Vd) significantly improved outcomes versus Vd in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 CASTOR study. We report the results of a prespecified interim analysis of the phase 3 LEPUS study of D-Vd versus Vd in Chinese patients with RRMM.Patients and MethodsChinese patients with ≥ 1 prior line of therapy were randomized 2:1 to receive 8 cycles (21 days/cycle) of bortezomib (1.3 mg/m² subcutaneously) and dexamethasone (20 mg orally/intravenously) ± daratumumab (16 mg/kg intravenously). The primary endpoint was progression-free survival (PFS).ResultsA total of 211 patients were randomized (D-Vd, 141; Vd, 70). After an 8.2-month median follow-up, D-Vd significantly prolonged PFS versus Vd (median, not reached vs. 6.3 months; hazard ratio, 0.28; 95% confidence interval, 0.17-0.47; P < .00001) and significantly improved the rates of overall response (83% vs. 65%; P = .00527), ≥ very good partial response (65% vs. 33%; P = .00002), ≥ complete response (33% vs. 11%; P = .00079), and minimal residual disease negativity (10^–5 sensitivity; 22% vs. 3%; P = .0002). The PFS benefit of D-Vd versus Vd was maintained across prespecified subgroups, including patients with prior bortezomib treatment and with high-risk cytogenetics. Thrombocytopenia (D-Vd, 51%; Vd, 37%), lymphopenia (44%; 29%), and lung infection (30%; 22%) were the 3 most common grade 3/4 treatment-emergent adverse events. Although patients in both treatment groups experienced higher rates of grade 3/4 lymphopenia and infections versus patients in CASTOR, the safety profile was generally consistent with that of CASTOR.ConclusionThese data support the use of D-Vd in Chinese patients with RRMM.     

沙立度胺联合地塞米松治疗初发多发性骨髓瘤25例

目的观察沙立度胺联合地塞米松方案治疗多发性骨髓瘤的疗效及其不良反应。方法沙立度胺,口服,起始剂量每天50mg,50mg每晚顿服,根据患者耐受情况每周增加剂量50mg/d,直到最大剂量达到400mg/d。地塞米松40mg/d,第1～4日,第9～12日,第17～20日分别静脉或口服给药,每28日为1个疗程。该方案治疗至少3个月。结果完全缓解4例(16%),部分缓解6例(24%),进展10例(40%),无效5例(20%),总有效率80%。常见的不良反应为便秘、嗜睡、疲乏、水肿、指端麻木等。结论沙立度胺联合地塞米松是初治多发性骨髓瘤有效的治疗方案,不良反应少。     

三氧化二砷、沙利度胺和地塞米松联合治疗复发性、难治性多发性骨髓瘤

[目的]探索治疗复发性、难治性多发性骨髓瘤（MM）的有效方法。[方法]经传统化疗方案和干扰素等治疗后复发、再次治疗困难或无效的MM患者共45例，给予三氧化二砷（As2O3）10mg／d，静脉滴注，第1～28天；地塞米松（DXM）40mg／d，第1～4、9～12、17～20、25～28天：沙利度胺（THL）200mg／d，第1～28天。每4周1个疗程，休息4周，连用2个疗程评价疗效。[结果]95．6％（43／45）患者均有效，其中37．8％（17／45）获PR，57．8％（26／45）获有效。6个月无进展生存率（PFS）和12个月PFS分别为89.3％和73.2％。大部分患者都有不同程度的水钠潴留症状，均未见明显骨髓抑制。[结论]三氧化二砷、沙利度胺和地塞米松联合方案是治疗复发性、难治性MM的有效并安全的方法。     

Clinical Study of Thalidomide Combined with Dexamethasone for the Treatment of Elderly Patients with Newly Diagnosed Multiple Myeloma

Objective: To investigate the relationship between the efficacy and safety of different doses of thalidomide(Thal) plus dexamethasone (Dex) as the initial therapy in elderly patients with newly diagnosed multiplemyeloma (MM). Methods: Clinical data of 28 elderly patients with newly diagnosed MM who underwent theTD regimen as the initial therapy were analyzed retrospectively. The patients were divided into two groupsaccording to the maximal sustained dose of Thal: lower dose (group A) and higher dose (group B). The overallresponse rate (ORR), progression free survival (PFS), overall survival (OS), and adverse events (AES) werecompared between the two groups. Results: A total of 28 patients were followed up with a median of 18 months.The ORR was 60.1%. The median response time and PFS were 2.0 and 17.0 months, respectively. The meansustained dose of Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg, P=0.01). Therewas no significantly difference in ORR (57.1% v 64.3%, P=1.00) and PFS (9.63months v 17.66 months, P=0.73)between groups A and B. During the follow up, only five patients died (<40%) and, therefore, median OS valueswere not available. It is estimated, however, that the mean survival time in the two groups was 35.6 and 33.4months (P>0.05), respectively. All of the patients tolerated the treatment well. The incidence of AES in patientswith a grading above 3 in group B was significantly higher than in group A (P=0.033). Conclusions: The TDregimen results in a high response rate and manageable AES as the initial therapy in elderly patients with MM.TD should be considered as the front line regimen for the treatment of elderly patients with MM in areas withfinancial constraints. The clinical response can be achieved at a low dose Thal with minimal toxicity.     

Daratumumab,Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR

BackgroundIn the phase III CASTOR study in relapsed or refractory multiple myeloma, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone. Outcomes after 40.0 months of median follow-up are discussed.Patients and MethodsEligible patients had received ≥ 1 line of treatment and were administered bortezomib (1.3 mg/m²) and dexamethasone (20 mg) for 8 cycles with or without daratumumab (16 mg/kg) until disease progression.ResultsOf 498 patients in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247), 47% had 1 prior line of treatment (1PL; D-Vd, n = 122; Vd, n = 113). Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001) and the 1PL subgroup (27.0 vs. 7.9 months; HR, 0.22; 95% CI, 0.15-0.32; P < .0001). In lenalidomide-refractory patients, the median PFS was 7.8 versus 4.9 months (HR, 0.44; 95% CI, 0.28-0.68; P = .0002) for D-Vd (n = 60) versus Vd (n = 81). Minimal residual disease (MRD)–negativity rates (10⁻⁵) were greater with D-Vd versus Vd (ITT: 14% vs. 2%; 1PL: 20% vs. 3%; both P < .0001). PFS2 was significantly prolonged with D-Vd versus Vd (ITT: HR, 0.48; 95% CI, 0.38-0.61; 1PL: HR, 0.35; 95% CI, 0.24-0.51; P < .0001). No new safety concerns were observed.ConclusionAfter 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D-Vd provided the greatest benefit at first relapse and increased MRD-negativity rates.     

Thalidomide/estramustine/paclitaxel in metastatic androgen-independent prostate cancer

Background

This is a phase I/II trial of thalidomide with estramustine and paclitaxel in men with androgen-independent prostate cancer (AIPC) who underwent previous chemotherapy.

Patients and Methods

Men with progressive AIPC were treated with oral thalidomide (200 mg, 400 mg, or 600 mg daily), intravenous paclitaxel (100 mg/m² over 3 hours on days 3 and 10), and oral estramustine (140 mg 3 times daily on days 1-5 and days 8-12) every 21 days.

Results

Phase I: first cycle dose-limiting toxicity occurred in 0 of 3 patients at 200 mg thalidomide daily, 0 of 3 at 400 mg daily, and 1 of 3 at 600 mg daily (the designated maximum tolerated dose). Phase II: twenty-nine of 38 evaluable patients (76%; 95% confidence interval, 67%-87%) experienced a 50% decrease in prostate-specific antigen level. Five of 18 patients (28%) with measurable disease exhibited an objective response. Nine of 14 patients (64%) with disease refractory to previous taxane therapy had 50% decreases in prostate-specific antigen level. Grade 3/4 adverse events included neutropenia (9 of 39 [23%]), fatigue (9 of 39 [23%]), dyspnea (8 of 39 [21%]), and thromboembolic events (7 of 39 [18%]). Cumulative dose-limiting toxicity rates were minimal (13%) with thalidomide at 200 mg daily.

Conclusion

The profile of activity of thalidomide/paclitaxel/estramustine in taxane-refractory AIPC warrants further investigation.     

Induction Treatment With Cyclophosphamide,Thalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: A Phase II Study

Background:Thalidomide has alternative mechanisms of action; it can be combined with dexamethasone or alkylating agents for the treatment of multiple myeloma (MM); however, the optimal doses and appropriate intervals of thalidomide continue to be debated.Patients and Methods:We assessed the clinical efficacy and toxicity of thalidomide in patients with newly diagnosed MM; 68 patients were treated with pulsed cyclophosphamide, thalidomide, and dexamethasone (CTD) chemotherapy for induction treatment.Results:After a median of 28 months' follow-up, the overall response rate was 79.4%, with a 42.6% complete response (CR) or very good partial response (VGPR). Patients with cytogenetically high-risk disease had poor CR/VGPR rates (27.3%) at a median of 11.5 months of time to progression (TTP) compared with patients with standard-risk disease who achieved CR/VGPR rates (50%) at a median of 20.3 months of TTP. The major adverse events included peripheral sensory neuropathy (14.3%), infection (10.2%), and thromboembolic complications (5.9%). Thirty-two patients who achieved more than a PR proceeded to peripheral blood stem cell collection with a median number of 5.0 × 10⁶ CD34⁺ cells/kg collected.Conclusion:CTD resulted in a favorable response with tolerable toxicity in patients with MM and did not affect the yield of the stem cell collection.     

Thalidomide/Estramustine/Paclitaxel in Metastatic Androgen-Independent Prostate Cancer

BackgroundThis is a phase I/II trial of thalidomide with estramustine and paclitaxel in men with androgen-independent prostate cancer (AIPC) who underwent previous chemotherapy.Patients and MethodsMen with progressive AIPC were treated with oral thalidomide (200 mg, 400 mg, or 600 mg daily), intravenous paclitaxel (100 mg/m² over 3 hours on days 3 and 10), and oral estramustine (140 mg 3 times daily on days 1-5 and days 8-12) every 21 days.ResultsPhase I: first cycle dose-limiting toxicity occurred in 0 of 3 patients at 200 mg thalidomide daily, 0 of 3 at 400 mg daily, and 1 of 3 at 600 mg daily (the designated maximum tolerated dose). Phase II: twenty-nine of 38 evaluable patients (76%; 95% confidence interval, 67%-87%) experienced a 50% decrease in prostate-specific antigen level. Five of 18 patients (28%) with measurable disease exhibited an objective response. Nine of 14 patients (64%) with disease refractory to previous taxane therapy had 50% decreases in prostate-specific antigen level. Grade 3/4 adverse events included neutropenia (9 of 39 [23%]), fatigue (9 of 39 [23%]), dyspnea (8 of 39 [21%]), and thromboembolic events (7 of 39 [18%]). Cumulative dose-limiting toxicity rates were minimal (13%) with thalidomide at 200 mg daily.ConclusionThe profile of activity of thalidomide/paclitaxel/estramustine in taxane-refractory AIPC warrants further investigation.     

Laparoscopic Versus Open Resection for Gastrointestinal Stromal Tumors (GISTs)

Purpose

Primary gastrointestinal stromal tumors (GISTs) are typically treated with open resection. There is growing interest in laparoscopic GIST resection; however, data is limited. We report our experience with GIST resections using both open and laparoscopic techniques.

Materials and Methods

Twenty-nine GIST patients underwent definitive intent resection at the University of Missouri from 1990 to 2010. Patients who underwent laparoscopic resection (n?=?7) were matched on the basis of tumor size, age, tumor location, and National Comprehensive Cancer Network (NCCN) risk stratification with seven patients who underwent open resection. The two groups were compared with respect to age, gender, BMI, tumor size, tumor site, mitotic rate, surgical margins, NCCN risk stratification, estimated blood loss, hospital stay, surgical complications, disease recurrence, and overall survival.

Results

The cohorts did not differ with respect to age, gender, BMI, tumor location, tumor size, or positive margins (p?>?0.05). Patients who underwent open resection had more NCCN high-risk patients, but the difference was not statistically significant (p?=?0.08). There was significantly less estimated blood loss (median 15 vs. 150 mL, p?<?0.05) and significantly shorter hospital stay (median 4 vs. 7 days, p?<?0.05) for the laparoscopy group. There were no recurrences in the laparoscopy group, but there was one in the open group with a median follow-up of 55 and 63 months, respectively (p?>?0.05). Five-year disease-free survival was 100 % for the laparoscopic group and 83 % for the open resection group.

Conclusions

Laparoscopic resection for appropriately selected GISTs is feasible and associated with significantly less blood loss and shorter hospitalizations compared to open resection. Further studies are needed to better define its role for GIST.

     

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies

IntroductionMelphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN.MethodsThese analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022).ResultsIn OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports.ConclusionThese analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).