Immunosuppressive Therapy for Patients With Myelodysplastic Syndrome: A Prospective Randomized Multicenter Phase III Trial Comparing Antithymocyte Globulin Plus Cyclosporine With Best Supportive Care—SAKK 33/99

2011 ◽  
Vol 29 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Jakob R. Passweg ◽  
Aristoteles A.N. Giagounidis ◽  
Mathew Simcock ◽  
Carlo Aul ◽  
Christiane Dobbelstein ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Supportive Care ◽  
Antithymocyte Globulin ◽  
Group Performance ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Refractory Anemia ◽  
Phase Iii Trial ◽  
Hematologic Response ◽  
The Impact

Purpose Immunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective in patients with immune-mediated marrow failure. Patients and Methods This trial was designed to assess the impact of immunosuppression on hematopoiesis, transfusion requirements, transformation, and survival in patients with MDS randomly assigned to 15 mg/kg of horse ATG for 5 days and oral CSA for 180 days (ATG+CSA) or best supportive care (BSC), stratified by treatment center and International Prognostic Scoring System (IPSS) risk score. Primary end point was best hematologic response at 6 months. Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤ 2 and transfusion dependency of less than 2 years in duration. Results Between 2000 and 2006, 45 patients received ATG+CSA (median age, 62 years; range, 23 to 75 years; 56% men) and 43 patients received BSC (median age, 65 years; range, 24 to 76 years; 81% men). IPSS score was low, intermediate-1, intermediate-2, high, and not evaluable in eight, 24, seven, one, and five patients on ATG+CSA, respectively, and eight, 25, five, zero, and five patients on BSC, respectively. Refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess of blasts (RAEB) -I, RAEB-II, and hypoplastic disease were present in 21, six, nine, zero, and nine patients on ATG+CSA, respectively, and 18, eight, 11, two, and four patients on BSC, respectively. By month 6, 13 of 45 patients on ATG+CSA had a hematologic response compared with four of 43 patients on BSC (P = .0156). Two-year transformation-free survival (TFS) rates were 46% (95% CI, 28% to 62%) and 55% (95% CI, 34% to 70%) for ATG+CSA and BSC patients, respectively (P = .730), whereas overall survival (OS) estimates were 49% (95% CI, 31% to 66%) and 63% (95% CI, 42% to 78%), respectively (P = .828). Conclusion This open-label randomized phase III trial demonstrates that ATG+CSA treatment seems to be associated with hematologic response in a subset of patients without apparent impact on TFS and OS.

Salvage Chemotherapy for Pretreated Gastric Cancer: A Randomized Phase III Trial Comparing Chemotherapy Plus Best Supportive Care With Best Supportive Care Alone

2012 ◽  
Vol 30 (13) ◽  
pp. 1513-1518 ◽  
Author(s):  
Jung Hun Kang ◽  
Soon Il Lee ◽  
Do Hyoung Lim ◽  
Keon-Woo Park ◽  
Sung Yong Oh ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Supportive Care ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Best Supportive Care ◽  
Salvage Chemotherapy ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Prior Chemotherapy ◽  
Pretreated Patients

Purpose When designing this trial, there was no evidence that salvage chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial prolongation of survival when compared with best supportive care (BSC). However, SLC is often offered to pretreated patients with AGC for anecdotal reasons. Patients and Methods Patients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC—either docetaxel 60 mg/m2 every 3 weeks or irinotecan 150 mg/m2 every 2 weeks—was left to the discretion of investigators. Primary end point was overall survival (OS). Results Median OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to 0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the prospectively defined subgroups, including age, PS, number of prior treatments, metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was generally well tolerated, and adverse events were similar in the SLC and BSC arms. We found no median OS difference between docetaxel and irinotecan (5.2 v 6.5 months; P = .116). Conclusion To our knowledge, this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.

Low-Dose Decitabine Versus Best Supportive Care in Elderly Patients With Intermediate- or High-Risk Myelodysplastic Syndrome (MDS) Ineligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

2011 ◽  
Vol 29 (15) ◽  
pp. 1987-1996 ◽  
Author(s):  
Michael Lübbert ◽  
Stefan Suciu ◽  
Liliana Baila ◽  
Björn Hans Rüter ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Supportive Care ◽  
Low Dose ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Patient Reported ◽  
Grade 3

Purpose To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. Patients and Methods Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and the median MDS duration at random assignment was 3 months. Primary end point was overall survival (OS). Decitabine (15 mg/m2) was given intravenously over 4 hours three times a day for 3 days in 6-week cycles. Results OS prolongation with decitabine versus BSC was not statistically significant (median OS, 10.1 v 8.5 months, respectively; hazard ratio [HR], 0.88; 95% CI, 0.66 to 1.17; two-sided, log-rank P = .38). Progression-free survival (PFS), but not acute myeloid leukemia (AML) –free survival (AMLFS), was significantly prolonged with decitabine versus BSC (median PFS, 6.6 v 3.0 months, respectively; HR, 0.68; 95% CI, 0.52 to 0.88; P = .004; median AMLFS, 8.8 v 6.1 months, respectively; HR, 0.85; 95% CI, 0.64 to 1.12; P = .24). AML transformation was significantly (P = .036) reduced at 1 year (from 33% with BSC to 22% with decitabine). Multivariate analyses indicated that patients with short MDS duration had worse outcomes. Best responses with decitabine versus BSC, respectively, were as follows: complete response (13% v 0%), partial response (6% v 0%), hematologic improvement (15% v 2%), stable disease (14% v 22%), progressive disease (29% v 68%), hypoplasia (14% v 0%), and inevaluable (8% v 8%). Grade 3 to 4 febrile neutropenia occurred in 25% of patients on decitabine versus 7% of patients on BSC; grade 3 to 4 infections occurred in 57% and 52% of patients on decitabine and BSC, respectively. Decitabine treatment was associated with improvements in patient-reported quality-of-life (QOL) parameters. Conclusion Decitabine administered in 6-week cycles is active in older patients with higher-risk MDS, resulting in improvements of OS and AMLFS (nonsignificant), of PFS and AML transformation (significant), and of QOL. Short MDS duration was an independent adverse prognosticator.

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