Continuous fluropyrimidine (FP) with platinum (P) based chemotherapy (CT) versus maintenance FP after induction therapy in advanced gastric (G) and gastroesophageal (GE) cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 375-375
Author(s):  
Daniel Walden ◽  
Mohamad Bassam Sonbol ◽  
Skye Buckner Petty ◽  
Mitesh J. Borad ◽  
Tanios S. Bekaii-Saab ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Induction Therapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Significant Difference ◽  
Potential Benefits ◽  
Ct Data ◽  
Grade 3 ◽  
Improve Patient ◽  
Continuous Induction

375 Background: Combination FP with P CT have become the standard of care for advanced G/GEJ cancer. Clinical trials in conjunction with practice, have adopted induction FP and P CT for 3-4 months (mos). In other GI malignancies, induction CT followed by maintenance CT (MTC) has been shown to improve patient (pt) outcomes compared to observation, with a decrease in treatment (trmt) related toxicities with induction therapy. However a maintenance approach in G/GEJ cancer has not been investigated in clinical trials. We investigated pt outcomes with metastatic G/GEJ cancer who received continuous induction (CTX) versus induction followed by MTC. Methods: A retrospective analysis of pts with metastatic G/GEJ adenocarcinoma treated with (FP+ P)-based CT between 2007 to 2017 from three centers of a single institution was performed. Metastatic G/GEJ cancer pts who achieved at least stable disease after initial induction trmt were included. Pts were categorized into the CTX group if they received greater than 16 weeks or 8 cycles of combined CT and assigned to the MTC group if they received maintenance FP monotherapy after 8 or less cycles of combined induction CT. Data was extracted from the medical record to determine progression free survival (PFS), overall survival (OS), and toxicities. Results: Sixty-four pts that met criteria and were evaluated, thirty-four received CTX and thirty received MTC. No significant difference in PFS (12.1 vs 8.0 mos p = .72, HR=1.10 95%CI .66-1.83) was observed between the CTX and MTC groups, additionally there was no significant difference in OS. A significant decrease in trmt related toxicities were observed, with a higher proportion of thrombocytopenia (84.8% vs 50.0% p = .004), and grade 3 neuropathy (39.4% vs 13.8% p =.024) in CTX pts (Table). Conclusions: MTC following induction FP/P CT is associated with an improved toxicity profile and appears to be effective compared to CTX in metastatic G/GEJ cancer. Prospective randomized studies confirming its potential benefits compared with continuous induction CT are warranted. [Table: see text]

scholarly journals A Comparison Between Chemo-Radiotherapy Combined With Immunotherapy and Chemo-Radiotherapy Alone for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Montserrat Lara-Velazquez ◽  
Jack M. Shireman ◽  
Eric J. Lehrer ◽  
Kelsey M. Bowman ◽  
Henry Ruiz-Garcia ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Combined Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Care Group ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Grade 3

BackgroundImmunotherapy for GBM is an emerging field which is increasingly being investigated in combination with standard of care treatment options with variable reported success rates.ObjectiveTo perform a systematic review of the available data to evaluate the safety and efficacy of combining immunotherapy with standard of care chemo-radiotherapy following surgical resection for the treatment of newly diagnosed GBM.MethodsA literature search was performed for published clinical trials evaluating immunotherapy for GBM from January 1, 2000, to October 1, 2020, in PubMed and Cochrane using PICOS/PRISMA/MOOSE guidelines. Only clinical trials with two arms (combined therapy vs. control therapy) were included. Outcomes were then pooled using weighted random effects model for meta-analysis and compared using the Wald-type test. Primary outcomes included 1-year overall survival (OS) and progression-free survival (PFS), secondary outcomes included severe adverse events (SAE) grade 3 or higher.ResultsNine randomized phase II and/or III clinical trials were included in the analysis, totaling 1,239 patients. The meta-analysis revealed no statistically significant differences in group’s 1-year OS [80.6% (95% CI: 68.6%–90.2%) vs. 72.6% (95% CI: 65.7%–78.9%), p = 0.15] or in 1-year PFS [37% (95% CI: 26.4%–48.2%) vs. 30.4% (95% CI: 25.4%–35.6%) p = 0.17] when the immunotherapy in combination with the standard of care group (combined therapy) was compared to the standard of care group alone (control). Severe adverse events grade 3 to 5 were more common in the immunotherapy and standard of care group than in the standard of care group (47.3%, 95% CI: 20.8–74.6%, vs 43.8%, 95% CI: 8.7–83.1, p = 0.81), but this effect also failed to reach statistical significance.ConclusionOur results suggests that immunotherapy can be safely combined with standard of care chemo-radiotherapy without significant increase in grade 3 to 5 SAE; however, there is no statistically significant increase in overall survival or progression free survival with the combination therapy.

Do elderly patients benefit from enrollment in phase I clinical trials?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9509-9509
Author(s):  
Wai Meng David Tai ◽  
Cindy Lim ◽  
Aziah Ahmad ◽  
Whee Sze Ong ◽  
SuPin Choo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Clinical Characteristics ◽  
Phase 1 ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
Phase I Clinical Trials ◽  
Lung Cancers ◽  
Significant Difference ◽  
Grade 3

9509 Background: Despite the significant burden of cancer in the older population, their outcomes in the context of phase I studies have been poorly studied. We evaluated the clinical characteristics and outcomes of elderly pts enrolled in phase 1 clinical trials in our centre and evaluate the performance of Royal Marsden Hospital (RMH) prognostic score (albumin, LDH, no of met sites) in this pt population. Methods: 296 consecutive pts who were treated in 20 phase 1 trials from 2005-2012 in our unit were analysed. Clinical characteristics and outcomes between young pts (<65, n=202) and older pts (≥65, n=94) were compared. Results: The median age of the older pts was 69 (65-84), 71% were males. 51% of the pts received chemotherapy based treatment with or w/out biological agents. 61% of the pts had lung cancers and 32% had gastrointestinal cancers. 52% of pts had ≥2 co-morbidities. After median follow up of 7.5 mths (0.36-50.6 mths), the median progression free survival (PFS) and overall survival (OS) were 5.8 and 8.8 mths respectively. Although elderly pts had more co-morbidities and lower albumin levels at baseline, there was no significant difference in survival (8.8 vs 9.9 mths), p=0.68) compared to younger pts. The prognostic factors for OS identified in multivariate analysis were prior lines of chemotherapy (0-2 vs ≥3), baseline sodium levels (≥135 vs <135mmol/L) and platelet levels (≤400 vs >400×10⁹). We developed a risk nomogram based on the factors identified prognostic of OS with concordance(c)-index of 0.65. RMH score (2-3 vs 0-1) predicted for OS with hazard ratio of 2.1, p=0.03 and c- index of 0.63. 26% of elderly pts experienced grade 3/4 toxicities in the first cycle of treatment. Common grade 3/4 toxicities were dermatological (25%), haematological (17%) and gastrointestinal (13%). Both age of pts (p=0.70) and dose levels (p=0.18) did not have any bearing on occurrence of grade 3/4 toxicities. Conclusions: Elderly pts (≥65) enrolled into phase 1 clinical trials had similar survival outcomes and toxicity profiles compared to younger pts. Risk scoring models to aid patient selection need further clarification in this population.

scholarly journals Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

2021 ◽  
Author(s):  
Yang Wang ◽  
Jun Nie ◽  
Ling Dai ◽  
Weiheng Hu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Significant Difference ◽  
Grade 3 ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p  = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

scholarly journals Safety and Efficacy of Four Drug Versus Three Drug Regimens Among Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Saad Ullah Malik ◽  
Nazma Hanif ◽  
Priyanka Kumari ◽  
Khadija Noor Sami ◽  
Chase Warner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Standard Of Care ◽  
Drug Regimen ◽  
P Value ◽  
Newly Diagnosed ◽  
Drug Regimens ◽  
Grade 3

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 &gt;50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value:&lt;0.001, I2: 0%). Also, OS improved significantly in four drug regimen group (HR: 0.62, 95% CI: 0.51-0.76, p-value:&lt;0.001, I2: 3.5%). There was no statistically significant difference in any grade ≥3 hematologic adverse events when 4 vs 3 drug regimens were compared (RR: 1.26, 95% CI: 0.93-1.73, p-value:0.14, I2: 93%). Sensitivity analysis after removing D-VTd regimen from any grade ≥3 hematologic adverse events revealed similar results (RR: 1.05, 95% CI: 0.97-1.13, p-value:0.23, I2: 23%) confirming the robustness of analysis. When each hematologic adverse event was looked at separately, there was no difference between 4 vs 3 drug regimen in rates of anemia (RR: 0.99, 95% CI: 0.76-1.28, p-value:0.92, I2: 0%), neutropenia (RR: 1.39, 95% CI: 1.00-1.94, p-value:0.05, I2: 85%) and thrombocytopenia (RR: 1.13, 95% CI: 0.92-1.39, p-value:0.24, I2: 33%). There was low risk of bias and strength of evidence was of moderate. Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1077-1077
Author(s):  
Joyce O'Shaughnessy ◽  
Kevin Punie ◽  
Mafalda Oliveira ◽  
Filipa Lynce ◽  
Sara M. Tolaney ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Antibody Drug Conjugate ◽  
Phase 3 ◽  
Chemotherapy Agent ◽  
Recist 1.1 ◽  
Duration Of Response ◽  
Grade 3

1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

scholarly journals Efficacy and safety of combined androgen blockade with antiandrogen for advanced prostate cancer

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Y. Yang ◽  
R. Chen ◽  
T. Sun ◽  
L. Zhao ◽  
F. Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
First Line ◽  
Combined Androgen Blockade ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Grade 3 ◽  
Androgen Blockade

Background Combined androgen blockade (cab) is a promising treatment modality for prostate cancer (pca). In the present meta-analysis, we compared the efficacy and safety of first-line cab using an antiandrogen (aa) with castration monotherapy in patients with advanced pca.Methods PubMed, embase, Cochrane, and Google Scholar were searched for randomized controlled trials (rcts) published through 12 December 2016. Hazard ratios (hrs) with 95% confidence intervals (cis) were determined for primary outcomes: overall survival (os) and progression-free survival (pfs). Subgroup analyses were performed for Western compared with Eastern patients and use of a nonsteroidal aa (nsaa) compared with a steroidal aa (saa).Results Compared with castration monotherapy, cab using an aa was associated with significantly improved os (n = 14; hr: 0.90; 95% ci: 0.84 to 0.97; p = 0.003) and pfs (n = 13; hr: 0.89; 95% ci: 0.80 to 1.00; p = 0.04). No significant difference in os (p = 0.71) and pfs (p = 0.49) was observed between the Western and Eastern patients. Compared with castration monotherapy, cab using a nsaa was associated with significantly improved os (hr: 0.88; 95% ci: 0.82 to 0.95; p = 0.0009) and pfs (hr: 0.85; 95% ci: 0.73 to 0.98; p = 0.007)—a result that was not achieved with cab using a saa. The safety profiles of cab and monotherapy were similar in terms of adverse events, including hot flushes, impotence, and grade 3 or 4 events, with the exception of risk of diarrhea and liver dysfunction or elevation in liver enzymes, which were statistically greater with cab using an aa.Conclusions Compared with castration monotherapy, first-line cab therapy with an aa, especially a nsaa, resulted in significantly improved os and pfs, and had an acceptable safety profile in patients with advanced pca.

scholarly journals EPID-07. HEMATOLOGICAL ADVERSE EVENTS IN GLIOBLASTOMA PATIENTS TREATED WITH TEMOZOLOMIDE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi75-vi76
Author(s):  
Catherine Garcia ◽  
Zin Myint ◽  
Rani Jayswal ◽  
Allison Butts ◽  
Heidi Weiss ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Protective Factor ◽  
Significant Proportion ◽  
Progression Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
History Of ◽  
Grade 3 ◽  
Severe Grade

Abstract BACKGROUND Temozolomide (TMZ) is the cornerstone for glioblastoma (GBM) treatment. A significant proportion of patients develops hematologic toxicities with limited investigations on outcomes and risk factors for their development. METHODS Our study combines data from the two largest group trials, RTOG 0525 and RTOG 0825, to analyze serious hematologic adverse events (HAE) associated with TMZ therapy for GBM. We analyzed frequency and outcomes of HAE during chemoradiation. RESULTS 1154 patients were evaluated with a median age of 57 years. Over 79% of patients developed HAE during the entire course of GBM treatment. During chemoradiation the most common HAE during chemoradiation was lymphopenia (41.5%), followed by thrombocytopenia (39.0%), and anemia (35.3%). Of these, 34.1% were severe (Grade 3 or 4) and 65.9% were mild (grade 1 or 2). During maintenance the most common HAE was leukopenia (50.7%), followed by neutropenia (50.4%), and lymphopenia (45.3%). MGMT methylation was not associated with HAEs. A history of HAEs during chemoradiation was a protective factor for developing HAEs during maintenance. MGMT methylated and age younger than 50 were protective factors for mortality. Patients that presented HAEs anytime during treatment had a longer overall survival and progression free survival. There was no significant difference in survival between mild or severe HAEs. CONCLUSION HAE are common during chemoradiation with TMZ for GBM, but are more commonly grade 1 or 2 per CTCAE. HAE during GBM treatment is associated with decreased progression free survival and overall survival.

Meta Analysis of Grade 3 and/or 4 Toxicities in Low-Grade Non-Hodgkin Lymphoma (LG-NHL) Patients Receiving Maintenance Rituximab (MR) Therapy: Impact of Schedule on Toxicity

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2704-2704
Author(s):  
Chadi Nabhan ◽  
Dana Villines ◽  
Tina V. Valdez ◽  
Michele Ghielmini ◽  
Shu-Fang Hsu Schmitz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Research Funding ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Comparative Trial ◽  
Progression Free Survival ◽  
Low Grade ◽  
Front Line ◽  
Grade 3 ◽  
The Impact

Abstract Abstract 2704 Background: MR has improved the outcome and progression-free survival (PFS) in patients with follicular lymphoma (FL) in front-line and relapsed settings. However, maintenance schedules have been empirically designed based on either B-cell depletion kinetics or rituximab levels, with no consensus on the optimal regimen. Overall, toxicities have been predictable and tolerable but the impact of MR schedule on toxicities has not been previously reported and could influence selection of maintenance regimens. Methods: Using PubMed, prospective clinical trials employing MR were identified. Data presented in abstract form or at meetings were deemed incomplete and thus excluded. Data were analyzed from published manuscripts as percentages of subjects experiencing an adverse event (AE). Percentages were considered as the unit of analysis as this adjusted for the uneven sample sizes. Data were collected for overall Grade 3 and/or Grade 4 toxicity (AE reported at any phase of treatment) and was further categorized as AE occurring during initial treatment or during MR. Grade 1 and 2 toxicities were excluded from meta-analysis, given lack of consistent reporting. No grade 5 toxicities were reported. The incidence, severity, and type of toxicity was analyzed by type of induction (Rituximab (R) vs. R plus chemotherapy), histology (FL vs. FL plus other LG-NHL), setting (front-line vs. relapsed), and MR schedule (one dose every 2 months vs. one dose every 3 months vs. 4 doses every 6 months). Results: Nine clinical trials involving 1,928 patients were included in this Meta analysis (4 of which were randomized controlled in the MR phase). Of those, 1,004 patients received MR. The mean percentage of Grade 3/4 toxicities during any phase of treatment was 26% (95% CI = 0.12–51.88) but when restricted to the MR phase; it was 12.88% (95% CI = 6.50–19.26). Toxicities were numerically higher in patients receiving R induction plus chemotherapy versus R induction alone and in patients receiving MR for relapsed disease versus newly diagnosed patients, but did not reach statistical significance (P = 0.661 and 0.517, respectively). However, patients receiving MR every 2 months were significantly more likely to develop grade 3 and 4 toxicities compared to patients receiving MR every 6 months (P = 0.005). No statistical differences were demonstrated between the 2 vs. 3 months schedules or when comparing the 3 vs. 6 months schedules (P = 0.342 and 0.267, respectively) (Table 1). Statistically significant differences were also found in studies restricted to FL versus others allowing non-FL histologies (P = 0.025) with the FL patients experiencing more toxicity than others. The most frequently reported toxicities were neutropenia and infections. There were no treatment-related deaths in any of the arms. Conclusions: Approximately 13% of patients receiving MR experience grade 3 and/or 4 toxicities, mainly consisting of neutropenia and infections. MR given every 6 months appears to provide the least grade 3 and 4 toxicities. There is a suggestion of increased toxicity in FL histologies. It is important to note that this meta-analysis did not address efficacy and only a true comparative trial can definitively establish the relative risk/benefit ratios amongst MR schedules. Disclosures: Nabhan: Genentech: Research Funding, Speakers Bureau. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Smith:Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Treatment of glioblastoma in Venezuela: Limitations using the current standard of care

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13036-e13036
Author(s):  
E. I. Arbona-Roche ◽  
C. Sucre ◽  
R. Vera-Gimón ◽  
A. Vera-Gimón ◽  
R. Vera-Vera ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
High Rate ◽  
Phase Iii ◽  
Stevens Johnson Syndrome ◽  
Hematologic Toxicity ◽  
Current Standard ◽  
Johnson Syndrome ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

e13036 Background: The EORTC/NCIC phase III clinical trial using chemoirradiation with temozolomide (TMZ) 75 mg m-2 x 42d, followed by adyuvant TMZ 150–200 mg m-2 daily x 5d q28d x six cycles set a new standard of care for newly diagnosed glioblastoma (GBM). The applicability of this regimen in developing countries can be problematic. Objectives: To review our experience in Venezuela, contrasting overall survival (OS), 6-month progression-free survival (6PFS), and toxicity in our patients with corresponding outcomes from the EORTC/NCIC trial. Methods: We treated 30 patients with this regimen from March 2001 through July 2004. Results: The median age was 51 years; 17 (60%) were men; 27 (90%) had biopsy or partial resection; 27 (90%) took prophylactic anticonvulsants; and 23 (77%) had prophylaxis against P. jiroveci. Most patients (83%) took the full TMZ treatment during radiation, 7% interrupted TMZ during RT, and 10% could not afford the drug. One patient had Stevens-Johnson syndrome and did not complete RT. Twelve (40%) patients had stereotactic radiosurgery for recurrent disease during the adjuvant phase. The 24-month OS was 30%, median OS was 7.5 months, median PFS was 5 months, and 6PFS was 41%. SRS did not have any effect on OS (p = 0.17, logrank). Grade 3–4 hematologic toxicity was seen in two patients (7%). Conclusions: Except for differences in median OS (7.1 mo) and in 6-PFS (12.6 percentage points) all other measures were reasonably close to the EORTC/NCIC trial. Of concern is the high rate of anticonvulsant prophylaxis using enzyme-inducing drugs and the difficult access to TMZ. No significant financial relationships to disclose.

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