Long Term Follow-Up of the Gimema GSI 103 AMLE Randomized Trial: Daunoxome Seems To Improve Disease-Free Survival (DFS) of Elderly Patients with Acute Myelogenous Leukemia (AML).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1979-1979 ◽  
Author(s):  
Roberto Latagliata ◽  
Massimo Breccia ◽  
Simona Iacobelli ◽  
Paola Fazi ◽  
Giovanni Martinelli ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Univariate Analysis ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
Induction Treatment ◽  
Induction Phase ◽  
Long Term Follow Up ◽  
To Receive

Abstract The GSI 103 AMLE was a randomized phase III clinical trial to explore the efficacy of DaunoXome (DNX) versus Daunorubicin (DNR) standard treatment in AML elderly patients. From 10/2001 to 2/2004, 301 patients aged 61 to 75 years with a diagnosis of AML according to WHO classification and eligible for intensive chemotherapy were enrolled in this trial by 39 GIMEMA Centers. Patients were randomized to receive induction treatment with DNR (45 mg/sqm day 1 to 3) or DNX (80 mg/sqm day 1 to 3) plus AraC (100 mg/sqm day 1 to 7 by continuous infusion): as consolidation therapy, patients in CR received a further course of the assigned induction treatment. After the consolidation course, patients in CR underwent a 2nd randomization independently from the 1st random, to receive as maintenance therapy either AraC (20 mg twice daily day 1 to 10) plus all-trans retinoic acid (ATRA) (45 mg/sqm day 1 to 10) every 28 days for a maximum of 12 cycles (Arm A) or no further treatment (Arm B). 153 patients were enrolled in the DNR arm and 148 in the DNX arm: the two arms were comparable as to relevant patient characteristics, including karyotype. In the DNR arm, 77 patients (50.3%) achieved CR, 56 (36.6%) were resistant and 20 (13.1%) died during induction (ID). In the DNX arm, 73 patients (49.3%) achieved CR, 47 (31.8%) were resistant and 28 (18.9%) died during induction. Differences between the two arms at univariate analysis were not statistically significant either considering the 3 different types of response or considering ID versus other (Chi-square 0.34 and 0.17 respectively). After CR, the effect of DNX seems to be time-related, due to higher incidence of early deaths in CR (11% vs 3%, p=0.053) and lower incidence of relapse beyond 6 months (at 24 months 60% vs 80%, p=0.064). This translates in a cross of the OS and DFS curves between the two arms, with initial advantage for the DNR arm followed by an advantage for DNX arm after 12 months from diagnosis. A time-dependent covariate Cox model and a landmark analysis on patients in CR after 6 months revealed a better outcome of DNX patients (p= 0.029 and p=0.092, respectively) in the long term DFS follow-up. No difference has been observed in the DFS curves according to maintenance randomization. In conclusion, DNX is as effective as DNR in the induction phase of AML elderly patients, with a trend of increased early toxicity (ID + deaths in CR): however, DNX seems to improve the OS and DFS in the long-term follow-up of these patients, due to a reduction of late relapses. Further trials in more selected elderly patients or in younger patients will be helpful to define the exact role of DNX in AML.

Follow-up Analysis of a Randomized Comparison of Prolonged Myelosuppressive Maintenance Therapy Versus Intensive Consolidation Therapy as Postremission Therapy in AML.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1056-1056
Author(s):  
Utz O. Krug ◽  
Maria Cristina Sauerland ◽  
Bernhard J Woermann ◽  
Wolfgang Berdel ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Postremission Therapy ◽  
To Receive

Abstract Abstract 1056 Poster Board I-78 Introduction: We previously showed that a prolonged myelosuppressive maintenance chemotherapy was superior to S-HAM as a postremission therapy in patients > 16 years of age with AML after a TAD-HAM double induction therapy and TAD consolidation chemotherapy with regard to relapse-free survival (RFS) and borderline significance of the overall survival (OS) in responding patients (Buchner et al., JCO 2003, 21:4496-4504). Here we present long-term follow-up data with a median follow-up of 7.9 years from diagnosis and 7.1 years from the date of complete remission. Patients and Methods: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were upfront randomized in the AMLCG1992 study of the German AML Co-operative Group to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age ≥ 60 years] x 6 (HAM in patients ≥ 60 years only in case of blast persistence on day 16 of therapy) induction, TAD consolidation, and monthly maintenance with cycles of cytarabine combined with either daunorubicin (course 1), 6-thioguanine (course 2), cyclophosphamide (course 3), and again 6-thioguanine (course 4), and restarting with course 1 for 3 years, or to receive TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age ≥ 60 years) x 8 instead of maintenance. Results: A total of 576 patients (69.2%) achieved a complete remission (CR) those were 294 of 429 (68.5%) patients randomized to receive maintenance and 282 of 403 (70.0%) patients randomized to receive intensive consolidation S-HAM (p=n.s.). 190 patients received maintenance therapy as intended and 135 patients received an intensive consolidation therapy as intended. This prolonged follow-up analysis verified the superior relapse-free survival in all patients in the maintenance arm (10-year RFS 30.0 ± 5.6 versus 19.9 ± 6.1 %, p = 0.015). Stratified by age, the 10-year RFS was superior in younger patients < 60 years (36.9 ± 7.1 versus 25.2 ± 8.0 %, p = 0.038) and borderline significant in elderly patients (17.2 ± 4.5 versus 6.8 ± 6.2 %, p = 0.075). A subgroup analysis of known risk groups (lactate dehydrogenase (LDH) level < 700U/l versus ≥ 700U/l at diagnosis, cytogenetic risk profile, bone marrow blasts on day 16 after the start of the induction therapy) revealed a superior RFS in the subgroup of patients with LDH level > 700 U/l at diagnosis (33.5 ± 12.3 versus 18.2 ± 9.5 %, p = 0.043). This superior RFS also translated into a superior 10-year relapse-free interval (RFI) of all responding patients in the maintenance arm (35.7 ± 6.3 versus 27.6 ± 5.9 %, p = 0.015) with borderline significance in younger patients (42.9 ± 7.4 versus 35.0 ± 7.4 %, p = 0.053) and a significant difference in elderly patients (20.6 ± 10.0 versus 8.4 ± 7.5 %, p = 0.043). In this updated analysis, there was a trend, but no significant difference in the OS (maintenance arm: 10-year OS 24.3 ± 4.8, intensive consolidation arm: 19.7 ± 4.7 %, p = 0.148), and we verified a trend for a better OS in responding patients for the maintenance arm (10-year OS in responding patients 33.6 ± 7.5 versus 28.5 ± 6.2 %, p = 0.093). The event-free survival (EFS) also showed a trend towards better EFS in the maintenance arm (10-year EFS 20.7 ± 4.2 versus 14.8 ± 4.1 %, p = 0.082) which was significant in elderly patients (10-year EFS 10.5 ± 5.5 versus 3.9 ± 3.7 %, p = 0.044). Discussion: This updated analysis with a long-term follow-up of median 7.9 years from diagnosis and 7.1 years from CR verified the superior RFS and the trend for enhanced OS in responding patients. These results suggest the superiority of a prolonged monthly myelosuppressive maintenance therapy as compared to intensive consolidation S-HAM after TAD-HAM induction and TAD consolidation. Disclosures: No relevant conflicts of interest to declare.

Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience.

1998 ◽  
Vol 16 (2) ◽  
pp. 702-706 ◽  
Author(s):  
S B Saxman ◽  
D Finch ◽  
R Gonin ◽  
L H Einhorn
Keyword(s):  
Germ Cell ◽  
Univariate Analysis ◽  
Germ Cell Tumors ◽  
Phase Iii ◽  
Term Survival ◽  
Favorable Prognosis ◽  
Significant Difference ◽  
Long Term Follow Up

PURPOSE In a previously reported randomized Southeastern Cancer Study Group (SECSG) trial, three cycles of chemotherapy were found to be equivalent to four cycles in patients with favorable-prognosis germ-cell cancer. We have conducted a follow-up analysis of patients treated at Indiana University (Indianapolis, IN) to compare long-term survival between the two groups and to examine factors associated with survival. PATIENTS AND METHODS Sixty-nine patients with minimal-stage and 49 patients with moderate-stage disseminated germ-cell tumors were randomized to either three or four courses of bleomycin, etoposide, and cisplatin (BEP) administered every 3 weeks. Median follow-up time is 10.1 years (range, 7 months to 12.6 years). Ninety-two percent of patients have an actual follow-up time of > 5 years, and 97.5% of patients have an actual follow-up time of > 3 years. RESULTS Survival analysis shows no significant difference between the two treatment groups in terms of overall (P = .80) or disease-free (P = .93) survival. Several clinical variables were examined by univariate analysis; only serum human chorionic gonadotropin (HCG) had an impact on survival. There were two disease-related deaths in 104 patients with HCG < or = 1,000 mIU/mL and five disease-related deaths in 14 patients with HCG greater than 1,000 mIU/mL (P < .001). Ninety-eight percent (95% CI, 95.2 to 100) of patients with favorable prognosis germ-cell tumor with an initial HCG of < or = 1,000 mIU/mL are alive without evidence of disease at 5+ years. CONCLUSION With long-term follow-up, there is no statistically significant difference in survival between three or four cycles of BEP chemotherapy in patients with favorable prognosis germ-cell carcinoma. Serum HCG elevation of greater than 1,000 mIU/mL is a significant predictor of poor outcome in patients with otherwise good-risk disease.

Comprehensive Geriatric Assessment-Adapted Chemotherapy in Elderly Patients (>70 years) with Diffuse Large B-Cell Non-Hodgkin's Lymphoma (DLBCL): Final Results and Long Term Follow-up.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2684-2684 ◽  
Author(s):  
Umberto Tirelli ◽  
Lucia Fratino ◽  
Monica Balzarotti ◽  
Lilj Uziel ◽  
Annalisa Giacalone ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Geriatric Assessment ◽  
Comprehensive Geriatric Assessment ◽  
Conflicts Of Interest ◽  
Long Term Follow Up ◽  
Good Score ◽  
Grade 3 ◽  
To Receive

Abstract Abstract 2684 Poster Board II-660 Background: R-CHOP is the standard treatment for elderly patients (pts) with DLBCL. Many pts aged 70 years (yrs) or more are unable to receive R-CHOP and the majority of them are excluded from clinical trials. Comprehensive geriatric assessment (CGA) is an useful instrument to predict the clinical outcome of elderly pts with cancer. Within the GOL (Gruppo Oncoematologico Linfomi) we started a phase II study aiming to evaluate feasibility and activity of a CGA-driven chemotherapy for elderly pts with DLBCL Material and methods: Pts with no comorbidity received CHOP/R-CHOP; pts with mild cardiopathy received epirubicin instead of doxorubicin; in pts with moderate/severe cardiopathy the use of anthracyclines was omitted; pts with diabetes did not receive prednisone; in pts with neuropathy vincristine was omitted. The dosage of chemotherapy was decided according to CGA: pts with a good score (ADL=6 and IADL>6) received full doses of CT; pts with an intermediate score (ADL=5 and IADL>4) received 75% of the dose; pts with a poor score (ADL<5 and IADL<5) received 50% of the dose. Results: One hundred pts (41 males and 59 females) have been treated. The median age was 75 yrs and stages III-IV were diagnosed in 51% of pts. 61% of pts received full doses of CT; 25% received 75% of dose and 14% received 50% reduced dose; 86% of pts received an anthracycline and 54% rituximab. Toxicity was quite acceptable. Grade 3–4 neutropenia was observed in 30% of pts, mucositis in 12%, and peripheral neuropathy in 9%. Four toxic deaths were observed. Overall, 81% of pts achieved complete remission; with a median follow-up of 50 months, 20% of them have relapsed. The 5 yr-OS, DFS, EFS are 58%, 78% and 50%. It is remarkable that the 5-year specific survival is 72%. Conclusions: Our results demonstrate that a CGA-driven approach is feasible in elderly pts with DLBCL. This strategy allows to offer a curative approach to all pts with aggressive NHL, avoiding to under treat pts with a potentially cured disease or over treat pts with severe comorbidities. Disclosures: No relevant conflicts of interest to declare.

Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9016-9016
Author(s):  
Luis G. Paz-Ares ◽  
Tudor-Eliade Ciuleanu ◽  
Jong-Seok Lee ◽  
Laszlo Urban ◽  
Reyes Bernabe Caro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Programmed Death ◽  
Long Term Follow Up ◽  
To Receive ◽  
Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1997 ◽  
Vol 15 (7) ◽  
pp. 2564-2569 ◽  
Author(s):  
S B Saxman ◽  
K J Propert ◽  
L H Einhorn ◽  
E D Crawford ◽  
I Tannock ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Intergroup Trial ◽  
Advanced Urothelial Carcinoma

PURPOSE A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. PATIENTS AND METHODS Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. RESULTS With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. CONCLUSION Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

Progression of aortic stenosis in elderly patients over long-term follow up

2013 ◽  
Vol 167 (4) ◽  
pp. 1226-1231 ◽  
Author(s):  
L.G. Kearney ◽  
M. Ord ◽  
B.F. Buxton ◽  
G. Matalanis ◽  
S.K. Patel ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Elderly Patients ◽  
Long Term Follow Up

Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial

2009 ◽  
Vol 27 (22) ◽  
pp. 3664-3670 ◽  
Author(s):  
Cyrille Hulin ◽  
Thierry Facon ◽  
Philippe Rodon ◽  
Brigitte Pegourie ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Standards Of Care ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
To Receive

Purpose Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. Patients and Methods Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. Results After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). Conclusion This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.

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