Survival After Recurrence of Ewing’s Sarcoma Family of Tumors

2005 ◽  
Vol 23 (19) ◽  
pp. 4354-4362 ◽  
Author(s):  
Lisa M. Barker ◽  
Thomas W. Pendergrass ◽  
Jean E. Sanders ◽  
Douglas S. Hawkins
Keyword(s):  
Relative Risk ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Medical Center ◽  
Univariate Analysis ◽  
Complete Response ◽  
High Dose ◽  
Line Treatment ◽  
Second Line ◽  
Risk Of Death

Purpose The overall survival (OS) of patients with relapsed Ewing’s sarcoma family of tumors (ESFT) is poor, and the relative benefit of high-dose therapy (HDT) is controversial. Patients and Methods We retrospectively identified 55 consecutive ESFT patients with adequate medical records for review, who were treated at Children’s Hospital and Regional Medical Center and who developed disease recurrence between January 1, 1985 and December 31, 2002. Results The median relapse-free interval (RFI) from diagnosis to first recurrence was 17 months (range, 5 to 90 months). Most recurrences were metastatic only (39 patients) or local and metastatic (10 patients). Twenty-seven patients (49%) achieved a partial or complete response to second-line treatment, with a median duration of response of 27 months (range, 5 to 119+ months). The 5-year OS rate for all relapsed patients was 23% (95% CI, 11% to 35%). By univariate analysis, improved OS was associated with response to second-line treatment versus no response (46% v 0%, respectively; P < .0001), RFI ≥ 24 months versus less than 24 months (48% v 12%, respectively; P = .0001), and no metastases at initial diagnosis versus presence of metastases (31% v 12%, respectively; P = .05). Because all 13 patients who received HDT also had responsive relapse, we performed a multivariate analysis. Reduced risk of death was associated with response to second-line therapy (relative risk, 0.14; 95% CI, 0.05 to 0.40), RFI ≥ 24 months (relative risk, 0.29; 95% CI, 0.13 to 0.66), and receiving HDT (relative risk, 0.26; 95% CI, 0.08 to 0.85). Conclusion HDT as consolidation therapy for relapsed ESFT seems to be associated with improved OS, even after adjusting for RFI and response to second-line treatment.

High-Dose Cytarabine Monotherapy Versus Intermediate Or High-Dose Cytarabine In Combination With Other Agents As Second-Line Salvage Therapy In Patients With Acute Myeloid Leukemia Who Did Not Respond To Initial Induction Therapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2695-2695
Author(s):  
Thu Oanh T Dang ◽  
Patrick Hilden ◽  
Sean M. Devlin ◽  
Raajit K. Rampal ◽  
Ross L. Levine ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Univariate Analysis ◽  
Patient Characteristics ◽  
Combination Group ◽  
High Dose ◽  
Second Line ◽  
Risk Of Death ◽  
High Dose Cytarabine ◽  
Group 2 ◽  
Group 1

Abstract Introduction Currently there is no standard for second-line salvage therapy in patients with acute myeloid leukemia (AML) who do not respond to initial induction therapy. The efficacy of current recommended second-line salvage regimens seems to be similar, but the tolerability can vary significantly. Anecdotally, high-dose cytarabine (HiDAC) monotherapy seems to be better tolerated than other recommended combination salvage regimens. Therefore, we conducted a retrospective analysis to evaluate the MSKCC experience with HiDAC monotherapy as compared to combination with other chemotherapeutic agents. Methods We included AML patients ≥ 18 years of age who did not respond to first induction therapy and received HiDAC (group 1; cytarabine 3g/m2 q12h for up to 12 doses) or intermediate- or high-dose cytarabine (1g/m2 or 3g/m2 at various numbers of doses) in combination with other agents (group 2) as second-line salvage, between the years 2003 and 2013. The combination group (group 2) consisted of regimens such as: MEC, CLAG, FLAG-I, and mitoxantrone or idarubicin with HiDAC. We evaluated the overall response rate (ORR), relapse free survival (RFS), and overall survival (OS). Univariate analysis was used to evaluate the potential association between outcomes and the following patient characteristics at the time of diagnosis: peripheral and marrow blast count, white blood cell count (WBC), platelet count, anthracycline agent used in first induction, cytogenetics risk, age, comorbidities (cardiac history, diabetes, hypertension, pulmonary, renal, and hepatic compromise), and AML subtype such as de novo (DN), antecedent (AHD), and treatment-related (t-AML). Results Group 1 (monotherapy) had 30 patients and group 2 (combination) had 77 patients. Patient characteristics were similar between the two groups with the exception of age, anthracycline type (daunorubicin vs idarubicin) used in first induction, and transplant status. Group 1 had more patients younger than 58 years old (median), more daunorubicin use, and more patients who underwent allogeneic stem cell transplantation. The side effects in group 1 were notable for pneumonia, C. diff, and bacteremia. The most notable side effects in group 2 were pneumonia, C. diff, bacteremia, sepsis, and treatment-related deaths. No statistically significant difference was observed in ORR (36.7% vs 33.3%; p = 0.922), RFS (9.3 vs 5.9 months; p = 0.53), and OS (12.9 vs 6.8 months; p = 0.329) between group 1 and group 2 respectively. Univariate screening showed no difference in ORR with respect to patient characteristics in group 1. In group 2, ORRs with regard to AML subtype were 64%, 28%, 8% for DN, AHD, t-AML respectively (p = 0.014), and a higher ORR was observed in patients with WBC ≥ 10 K/mcL (58.3% vs 41.7%; p = 0.051) and patients with good or intermediate cytogenetic risks (64% vs 36%; p = 0.017). For RFS, patients in group 1 with WBC > 10 K/mcL were associated with 3 times higher risk of relapse or death (p = 0.029). For RFS in group 2, patients with AHD and t-AML were associated with higher risk of relapse (HR (95% CI): 1.3 and 3.7 respectively, p = 0.002) compared to DN. For OS, patients in group 1 with WBC > 10 K/mcL were at 2.7 times higher risk of death (p = 0.049), an association which was not present in group 2. For OS, patients in group 2 with t-AML and AHD were at 4.2 times and 1.7 times higher risk of death than DN (p = 0.001) and this difference was not present in group 1. Patients with poor cytogenetic risks or comorbidities of interest did worse in terms of overall RFS (p < 0.001, p = 0.02 respectively) and OS (p < 0.001, p = 0.009 respectively). Outcomes did not seem to be associated with type of anthracycline used in first induction or platelet count at diagnosis. Conclusions Recognizing the limitations of a retrospective study, our analysis showed no difference in ORR, RFS, and OS for HiDAC monotherapy compared to intermediate- or high-dose cytarabine combinations. Our univariate analysis suggests statistically significant differences in ORR, RFS, and OS with regard to AML subtype, WBC at time of diagnosis, comorbidities, and cytogenetics risk. We are subcategorizing the combination group into intermediate-dose and high-dose cytarabine combination and compare them to monotherapy. We are looking at additional molecular genetics information besides NPM1, CEBPA, and FLT3 that could also influence outcomes. Disclosures: No relevant conflicts of interest to declare.

Patients with steroid-refractory toxicity following immune checkpoint inhibitors: Frequent hospitalizations and long duration of illness.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2655-2655
Author(s):  
Mia Bothwell ◽  
Aaron Cheng ◽  
Leyre Zubiri ◽  
Meghan Mooradian ◽  
Yevgeniy R. Semenov ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Academic Medical Center ◽  
Complete Response ◽  
Second Line ◽  
Duration Of Illness ◽  
Long Duration ◽  
Steroid Refractory

2655 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer with significantly improved outcomes, but these agents have a unique spectrum of toxicities known as immune-related adverse events (irAEs). The recommended treatment for non-endocrine toxicities is steroid based. However, a subset of patients (pts) is steroid-refractory and requires second-line immunosuppression. There is very little evidence regarding this population. In this retrospective study we report the 1) incidence 2) type of treatment used 3) natural history and 4) potential predictors of steroid-refractory irAE at a major academic medical center. Methods: The Research Patient Database Registry at Mass General Brigham was used to identify pts treated with an ICI from 1/5/2017 to 6/1/2019. Pharmaceutical records identified a subset of the cohort received a second-line immunosuppressive agent within a 15-month period after ICI. For pts with steroid-refractory irAE additional information was collected: demographics, ICI regimen, type/#/and severity of irAE, clinical characteristics, # of admissions, length of stay (LOS), amount and duration of steroid therapy, second line immunosuppression type, treatment discontinuation rates, response, and outcome of re-challenge. Multivariate logistic regressions were used to predict risk of refractory toxicity and study the association of different variables (age, sex, race, marital status, cancer and ICI types) with refractory toxicities. Results: We identified 61 pts (1.4%) with steroid-refractory irAEs (48 colitis, 4 myocarditis, 6 pneumonitis, 3 neurologic) out of the total ICI cohort (N=4,325). 60.7% received ICI monotherapy. 24.6% received ICI in the adjuvant setting. Median length of steroid duration was 68 days with max of 1135 days. Despite use of second line immunosuppression, 25.8% of pts were never able to discontinue steroids. Majority of pts (72.1%) had at least one hospitalization with median LOS of 7.5 days. 93.4% of pts permanently discontinued the ICI responsible for the irAE. Thirteen pts (21.3%) were later re-challenged with ICI and 7 (53.8%) of these developed a subsequent irAE. Anti-CTLA-4 therapy was associated with a 10-fold risk of refractory toxicity compared to PD-1 (p<.05). Best tumor response was complete response in 21.3% and partial response in 26.2%. Among different cancer types, melanoma was most strongly associated with refractory events (OR 2.97 in comparison to thoracic malignancy). Conclusions: Refractory toxicity is uncommon but leads to high rates of ICI discontinuation, frequent hospitalizations, and a long duration of illness with exposure to prolonged and high-doses of steroids. There is an urgent need for further investigation into predictive factors for steroid-refractory toxicity given that ICI is being used more frequently and in earlier lines of treatment.

scholarly journals Safety and Activity of Metronomic Temozolomide in Second-Line Treatment of Advanced Neuroendocrine Neoplasms

2019 ◽  
Vol 8 (8) ◽  
pp. 1224 ◽  
Author(s):  
Salvatore Tafuto ◽  
Claudia von Arx ◽  
Monica Capozzi ◽  
Fabiana Tatangelo ◽  
Manuela Mura ◽  
...  
Keyword(s):  
Performance Status ◽  
Complete Response ◽  
Neuroendocrine Neoplasms ◽  
Line Treatment ◽  
Second Line ◽  
Clinical Experiences ◽  
Significant Treatment ◽  
Platinum Based Chemotherapy ◽  
Suitable Treatment ◽  
And Performance

Background. Platinum-based chemotherapy is the mainstay of front-line treatment of patients affected by pluri-metastatic intermediate/high grade NeuroEndocrine Neoplasms (NENs). However, there are no standard second-line treatments at disease progression. Previous clinical experiences have evidenced that temozolomide (TMZ), an oral analog of dacarbazine, is active against NENs at standard doses of 150 to 200 mg/mq per day on days 1 to 5 of a 28-day cycle, even if a significant treatment-related toxicity is reported. Methods. Metastatic NENs patients were treated at the ENETS (European NeuroEndocrine Tumor Society) center of excellence of Naples (Italy), from 2014 to 2017 with a second-line alternative metronomic schedule of TMZ, 75 mg/m2 per os “one week on/one week off”. Toxicity was graded with NCI-CTC criteria v4.0; objective responses with RECIST v1.1 and performance status (PS) according to ECOG. Results. Twenty-six consecutive patients were treated. Median age was 65.5 years. The predominant primary organs were pancreas and lung. Grading was G2 in 11 patients, G3 in 15. More than half of patients had a PS 2 (15 vs. 11 with PS 1). The median time-on-temozolomide therapy was 12.2 months (95% CI: 11.4–19.6). No G3/G4 toxicities were registered. Complete response was obtained in 1 patient, partial response in 4, stable disease in 19 (disease control rate: 92.3%), and progressive disease in 2. The median overall survival from TMZ start was 28.3 months. PS improved in 73% of patients. Conclusions. Metronomic TMZ is a suitable treatment for G2 and G3 NENs particularly in PS 2 patients. Prospective and larger trials are needed to confirm these results.

Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study.

1996 ◽  
Vol 14 (12) ◽  
pp. 3056-3061 ◽  
Author(s):  
G J Creemers ◽  
G Bolis ◽  
M Gore ◽  
G Scarfone ◽  
A J Lacave ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Topoisomerase I ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Chemotherapeutic Regimen

PURPOSE Topotecan is a topoisomerase I inhibitor with preclinical activity against various tumor types. We conducted a large multicenter phase II study with topotecan in ovarian cancer in patients who had failed to respond to one prior cisplatin-based chemotherapeutic regimen. PATIENTS AND METHODS Topotecan 1.5 mg/m2/d was administered intravenously by 30-minute infusion for 5 days repeated every 3 weeks. As the cisplatin-free interval relates to response in subsequent treatment, patients were stratified in subgroups, ie, cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive. RESULTS One-hundred eleven patients entered the study. Nineteen patients were considered to be ineligible; 92 patients were assessable for response. A total of 552 courses were given (median, four per patient; range, one to 17). The major toxicities were leukocytopenia and neutropenia, which were grade 3 to 4 in 54.2% and 69.1% of courses, respectively, but with only 4.3% of these being grade 4 neutropenia plus fever or infectious complications. Prophylactic granulocyte colony-stimulating factor (G-CSF) was given in 20.5% of courses to maintain dose-intensity. Other relatively frequent side effects were alopecia (82%), nausea (36.4%), and vomiting (17.5%). The overall response rate was 16.3%, with one complete response (CR) and 14 partial responses (PRs). In the cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive strata, the response rates were 5.9%, 17.8%, and 26.7%, respectively. The median duration of time of documented response was 21.7 weeks (range, 4.6 to 41.9). CONCLUSION Topotecan in a daily-times-five schedule is an effective regimen as second-line treatment in ovarian cancer. Further investigations of topotecan in ovarian cancer, including first-line use and combination with other active agents, are indicated.

Effectiveness of Second Line Treatment in AL Amyloidosis Patients Refractory to M-Dex.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4930-4930
Author(s):  
Julie Abraham ◽  
Houria Debarri ◽  
Amelie Penot ◽  
Estelle Desport ◽  
Claire Aguilar ◽  
...  
Keyword(s):  
Light Chain ◽  
Complete Response ◽  
Free Light Chain ◽  
New Drugs ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
Front Line ◽  
Multicentric Study ◽  
Hematological Response

Abstract Abstract 4930 Purpose AL amyloidosis is a monoclonal disorder responsible for secretion of a monoclonal free light chain which will deposit as aggregated fibrils and cause organ dysfunction. Prognosis without treatment is poor with median survival around 1 year. Since our multicentric randomized trial comparing M-dex (oral Melphalan and Dexamethasone combination) and high dose treatment with stem cell support (Jaccard et al, NEJM 2007), M-Dex is our reference front line therapy in AL patients, whatever the risk group. Median survival with this strategy has dramatically improved, reaching 5 years in our study as well as in the Italian one (Palladini et al, Blood 2007). Nevertheless survival of refractory patients was poor in the absence of valuable rescue treatment between 2000 and 2005(Figure 1). New drugs as Thalidomide, Lenalidomide or Bortezomib, whose efficacy has been proven in multiple myeloma, has been reported to be effective and tolerable in AL patients. We performed a retrospective multicentric study to determine outcome of M-Dex refractory patients in the era of these new drugs. Patients and methods Patients with biopsy proven AL amyloidosis, treated with M-Dex, front line, since June 2006 were included if they were considered as refractory by there referent physician in 10 centres belonging to the French network for AL amyloidosis. We recorded the hematological response with second line treatment. Survival was analyzed from the first treatment date using Kaplan Meier model. Results We included 29 patients with a median age of 60 years (32-76), 16 patients had cardiac involvement, 19 renal involvement. The median number of organ involvement was 2 (1-5). Isotype of monoclonal light chain was kappa in 38% of cases, and lambda in 62%. Median abnormal free light chain level was 158 mg/L (25.9-2100). Twenty patients (69 %) were considered as non responders because they did not reached a 50% decrease in free light chain serum level and 9 patients (31%), who achieved a partial hematological response, because they did not have a clinical response. The median time between the first M-Dex cycle and the second line treatment was five months (1-17). Second line consisted in thalidomide in 5 patients, lenalidomide in 7 patients, and Bortezomib in 17 patients, in combination with sequential Dexamethasone. Hematological response occurred in 69% of the whole series, with 27% complete response. Depending on treatment, partial hematological response was obtained in 4/5 patients with thalidomide, 2/7 patients with lenalidomide, and 14/17 patients with bortezomib responded with 8 complete responses. With a median follow-up of 21 months (0-32) 69% of patients are alive (Figure 2). Conclusion As expected introduction of new drugs for treatment of refractory AL patients gives a high level of hematological response leading to a better survival. Bortezomib seems to be particularly attractive with hematological response rate of 82%, and 47% complete response. The combination of M-Dex and bortezomib will be compared soon with M-Dex in a prospective international multicentric study. Disclosures No relevant conflicts of interest to declare.

Real-World Clinical Outcomes By Cytogenetic Risk Category in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in France

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4784-4784
Author(s):  
Huamao Mark Lin ◽  
Keith L Davis ◽  
James A. Kaye ◽  
Katarina Luptakova ◽  
Lu Gao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Partial Response ◽  
Research Funding ◽  
Complete Response ◽  
Line Treatment ◽  
Second Line ◽  
High Risk Patients ◽  
Risk Patients ◽  
Standard Risk

Abstract INTRODUCTION: Multiple Myeloma (MM) is an incurable hematologic cancer characterized by multiple recurrences. With each recurrence, patients have a lower probability of response and duration of response is shorter. Therefore, there is an unmet need to improve outcomes in relapsed/refractory multiple myeloma (RRMM). There is a shortage of data describing clinical features and outcomes in these patients in real-world practice, particularly with regard to differences in outcomes by baseline cytogenetic risk. To help address this information gap, this study analyzed data from a cohort of RRMM patients in France. METHODS: A retrospective observational review of medical records was conducted in a cohort of 200 patients with RRMM in France. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 40 hematology/oncology providers across France practicing mainly in academic hospitals. Inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) first-line (induction) regimen of chemotherapy with or without stem cell transplant (SCT) and with or without other post-induction/SCT therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients could be alive or deceased at the time of record abstraction. Baseline cytogenetic risk was defined as follows: high-risk: cytogenetic abnormalities del(17p), t(4:14), or t(14;16); unknown/unassessed risk: patients for whom cytogenetics were unavailable; or standard-risk: all patients with known cytogenetics not classified as high-risk. Patients were assessed for treatment response, overall survival (OS) and progression-free survival (PFS) from date of first relapse (study index date). All analyses were descriptive. Survival was assessed using the Kaplan-Meier (K-M) method. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. A total of 55 high-risk and 113 standard-risk patients were identified; risk category was unknown or unassessed for 32 patients. Among all patients, mean (SD) age at RRMM diagnosis was 66.3 (8.9) years and 62% of the sample was male. Lenalidomide + dexamethasone was the most common second-line systemic regimen initiated (50% of high-risk patients, 59.5% of standard-risk patients receiving second-line treatment). A total of 114 patients (57%) initiated a third-line treatment. Despite clinical response in second-line treatment occurring sooner in high-risk patients (median: 106 days) than in standard-risk patients (median: 237 days), physician-assessed overall response rate (ORR) was lower in high-risk patients (63%: 17% complete response, 46% partial response) than standard-risk patients (91%: 26% complete response, 65% partial response) across all second-line treatments combined (Table 2).. For third-line treatment, ORR was lower in high-risk patients (54%: 12% complete response, 42% partial response) than standard-risk patients (74%: 9% complete response, 65% partial response). Among patients who initiated a second-line treatment (n = 192), 47.4% were deceased at the time of data collection. From second-line initiation, K-M estimates of 1- to 5-year OS and PFS were substantially lower for high-risk patients versus standard-risk. Specifically, the proportions of patients still alive 1, 3, and 5 years after second-line treatment initiation were 73%, 51%, and 36%, respectively, for high-risk patients and 94%, 73%, and 61% for standard-risk patients. The proportions of patients without disease progression at 1, 3, and 5 years after second-line initiation were 48%, 13.5%, and 5% for high-risk patients and 82%, 42%, and 14% for standard-risk patients. CONCLUSIONS: The importance of cytogenetic risk classification as a prognostic factor in RRMM was apparent in this retrospective review, in which patients with high-risk cytogenetics had less favorable outcomes in terms of ORR, OS, and PFS than standard-risk patients. Decreased response rate and lower PFS and OS was documented among patients with high-risk cytogenetics, which is in contrast to shorter time needed to achieve best clinical response in this subgroup. Results from this real-world study provide further confirmation of the unmet medical need presented by RRMM, especially for patients with high-risk cytogenetics. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Gao:Takeda: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

High dose chemotherapy with peripheral blood stem cell (P.B.S.C.) rescue in metastatic Ewing’s sarcoma at diagnosis

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 9004-9004
Author(s):  
A. Tienghi ◽  
S. Ferrari ◽  
M. Mercuri ◽  
P. Giovanis ◽  
E. Barbieri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Peripheral Blood Stem Cell ◽  
High Dose Chemotherapy ◽  
Blood Stem Cell ◽  
High Dose

Complete response (CR) to ifosfamide, gemcitabine, and vinorelbine (IGEV) and outcome in relapsed/refractory Hodgkin's lymphoma (HL) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8568-8568
Author(s):  
A. Anastasia ◽  
R. Mazza ◽  
L. Giordano ◽  
M. Balzarotti ◽  
M. Magagnoli ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Disease Status ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cox Proportional Hazard ◽  
Kaplan Meier

8568 Background: High dose chemotherapy with autologous stem cells transplant (ASCT) is the gold standard in patients with relapsed/refractory HL. Response to induction chemotherapy (chemosensitive patients) plays a major role in prognosis, however the role of CR status after induction therapy has not been established. Methods: One hundred twenty one patients with relapsed/refractory HL received 4 courses of IGEV followed by single (N=59) or tandem (N=19) ASCT (Santoro et al., Haematologica 92, 2007). Response to IGEV was evaluated by Cheson criteria (1999).The aim of this study was to evaluate the role of CR versus no-CR to IGEV induction therapy on the outcome in terms of progression free survival (PSF) and overall survival (OS). Statistical analysis was performed by using the Kaplan-Meier method and Cox proportional hazard model. Results: IGEV induced an overall response rate of 75% with 46% of CR. In the univariate analysis favourable factors for outcome were CR vs no-CR to IGEV (PFS: p <0.001, OS: p 0.002), A vs B symptoms (PFS: p 0.003; OS: p 0.05), limited vs advanced stage (PFS: p 0.03; OS: p 0.03), and 1 vs≥2 previous chemotherapy lines (PFS: p 0.03, OS: p 0.02); response to last therapy (relapsed vs refractory) influenced PFS (p 0.03) but not OS (p 0.70). The multivariate analysis confirmed the favourable prognostic role of CR to IGEV (PFS HR: 2.5, CI 95%:1.3; 4.6 - OS HR 2.3, CI 95%:1.1;4.8) and of the number of previous chemotherapy lines (PFS HR:1.8, CI 95%:1.0;3.2 - OS HR 2.1, CI 95%:1.1;3.9). Conclusions: According to our data, we conclude that: 1. CR to IGEV is the strongest indicator of outcome in relapsed/refractory HL. 2. Achievement of CR to IGEV overcomes the role of initial disease status. 3. Efforts are warranted to increase the CR rate by induction therapy. No significant financial relationships to disclose.

Resminostat in advanced hepatocellular carcinoma (HCC): Overall survival subgroup analysis of prognostic factors in the SHELTER trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15088-e15088 ◽  
Author(s):  
Michael Bitzer ◽  
Tom M. Ganten ◽  
Marcus A. Woerns ◽  
Jens T. Siveke ◽  
Matthias M. Dollinger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lower Risk ◽  
Vascular Invasion ◽  
Line Treatment ◽  
Second Line ◽  
Monotherapy Group ◽  
First Line ◽  
Treatment Groups ◽  
Risk Of Death ◽  
Baseline Characteristics

e15088 Background: Previously published results of the phase I/II SHELTER study demonstrated efficacy and safety of the novel pan-HDAC inhibitor resminostat in second-line treatment of HCC patients (pts) who had progressed under first-line sorafenib. As patient baseline characteristics might influence treatment outcome, an analysis of their potential influence on overall survival (OS) was performed. Methods: 45 pts with advanced-stage HCC and centrally confirmed radiologic progression under first-line sorafenib were included in a multi-center, two-arm trial. Resminostat was administered either alone or in combination with sorafenib. A Cox proportional-hazards model was used to evaluate the interaction between baseline characteristics and the effect of the two treatment groups on overall survival. Results: In the combination group, pts with Child-Pugh-A, ECOG 0 or absence of vascular invasion had a statistically significant lower risk of death compared to pts with Child-Pugh-B (HR 0.19, 95% CI 0.06-0.55), ECOG 1 (HR 0.15, 95% CI 0.05-0.44), or vascular invasion (HR 0.37, 95% CI 0.15-0.93), respectively. For pts with BCLC-B there was a strong trend, although not statistically significant, of a lower risk of death when compared to pts with BCLC-C (HR 0.43, 95% CI 0.13-1.49). Etiology, prior TACE therapy, extrahepatic spread and interval between first- and second-line treatment had no impact on overall survival in this study. Similar findings were observed in the monotherapy group. Comparing the impact of these baseline characteristics in the combination and monotherapy group, no statistically significant different influence on OS between both treatment groups was observed. Conclusions: Resminostat in combination with sorafenib provides a substantial OS benefit (median OS of 8.1 months) for advanced HCC patients who had developed progressive tumor disease under first-line sorafenib therapy. Subgroup analysis of patient baseline characteristics revealed a significant influence of Child-Pugh index, ECOG classification, and vascular invasion on overall survival, whereas e.g. the interval between first- and second-line treatment had no impact on overall survival. Clinical trial information: NCT00943449.

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