Efficacy and safety of radiotherapy (RT) plus temozolomide (TMZ) in elderly patients (EP) with glioblastoma (GBM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2043-2043 ◽  
Author(s):  
Giuseppe Lombardi ◽  
Luisa Bellu ◽  
Franco Berti ◽  
Patrizia Farina ◽  
Sara Galuppo ◽  
...  

2043 Background: the optimal management of EP with GBM remains controversial. The role of RT with TMZ for EP is unclear, and EP are often treated with RT alone, TMZ alone or palliative approaches. We describe our experience of combining RT with concurrent TMZ for treatment of EP with GBM Methods: medical records of patients ≥65 years old with newly GBM, histologically confirmed at Veneto Institute of Oncology – Padua, and treated with RT plus TMZ, were reviewed. Concomitant TMZ was 75mg/m2/die. The adjuvant treatment consisted of TMZ 150-200mg/m2/die for six cycles. Median progression-free survival(PFS) and overall survival(OS) were estimated with Kaplan-Meier method. Toxicity was scored according to CTCAE 4.0 Results: we analyzed 60 patients(PTS), 34 males and 26 females; the average age was 70 (range 65-82); ECOG PS was 0-1 in 35 PTS and 2 in 25 PTS; complete surgery was performed in 35 PTS, partial surgery in 25 PTS. 40 and 20 PTS received RT within 6 or more weeks (range 7-9) from surgery. MGMT and IDH1 were analyzed in 43 PTS: MGMT methylated in 20 PTS (46%), all PTS had wild-type IDH1. 34 PTS were treated with RT 40Gy in 15 fractions, 26 PTS with RT 60Gy in 30 fractions with no significant difference in ECOG PS, MGMT and type of surgery between the two subgroups. For all PTS, PFS and OS were 9.5 and 12.7 ms, respectively. OS was 13.7 and 12.4 ms (p=0.9) in PTS receiving RT within 6 or more weeks from surgery, respectively. 13% of PTS showed grade 3-4 haematological toxicity, 12% grade 3-4 asthenia, 3% nausea/vomiting. MGMT methylated and complete surgery was associated with a longer survival. PFS was 9 vs 10 months (p=0.4) and OS was 11.7 vs 13.7 ms (p=0.1), for PTS treated with 40Gy and 60Gy, respectively. Regarding toxicity: grade 3-4 haematological toxicity was 9% vs 23%, severe asthenia was 9% vs 15%, nausea/vomiting was 3% vs 4% of PTS receiving RT 40Gy and 60Gy, respectively. Conclusions: RT plus TMZ is effective and safe in EP with GBM and good ECOG PS. PFS and OS was not statistically different between PTS receiving RT 40Gy or 60Gy, although we showed a trend for longer OS with RT 60Gy; in contrast, severe toxicity was higher in PTS with RT 60Gy. OS was similar between PTS receiving RT within 6 or more weeks (7-9ws) from surgery.


2020 ◽  
Vol 20 (11) ◽  
pp. 887-895 ◽  
Author(s):  
Martina Catalano ◽  
Giandomenico Roviello ◽  
Raffaele Conca ◽  
Alberto D’Angelo ◽  
Valeria Emma Palmieri ◽  
...  

Background: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice. Methods: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. Results: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. Conclusions: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.



Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.



Author(s):  
Yang Wang ◽  
Jun Nie ◽  
Ling Dai ◽  
Weiheng Hu ◽  
Jie Zhang ◽  
...  

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.



BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunlong Huang ◽  
Xiaoyuan Gu ◽  
Xianshang Zeng ◽  
Baomin Chen ◽  
Weiguang Yu ◽  
...  

Abstract Background An upgraded understanding of factors (sex/estrogen) associated with survival benefit in advanced colorectal carcinoma (CRC) could improve personalised management and provide innovative insights into anti-tumour mechanisms. The aim of this study was to assess the efficacy and safety of cetuximab (CET) versus bevacizumab (BEV) following prior 12 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus BEV in postmenopausal women with advanced KRAS and BRAF wild-type (wt) CRC. Methods Prospectively maintained databases were reviewed from 2013 to 2017 to assess postmenopausal women with advanced KRAS and BRAF wt CRC who received up to 12 cycles of FOLFOXIRI plus BEV inductive treatment, followed by CET or BEV maintenance treatment. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rate. The secondary endpoint was the rate of adverse events (AEs). Results At a median follow-up of 27.0 months (IQR 25.1–29.2), significant difference was detected in median OS (17.7 months [95% confidence interval [CI], 16.2–18.6] for CET vs. 11.7 months [95% CI, 10.4–12.8] for BEV; hazard ratio [HR], 0.63; 95% CI, 0.44–0.89; p=0.007); Median PFS was 10.7 months (95% CI, 9.8–11.3) for CET vs. 8.4 months (95% CI, 7.2–9.6) for BEV (HR, 0.67; 95% CI 0.47–0.94; p=0.02). Dose reduction due to intolerable AEs occurred in 29 cases (24 [24.0%] for CET vs. 5 [4.8%] for BEV; p< 0.001). Conclusions CET tends to be superior survival benefit when compared with BEV, with tolerated AEs.



Author(s):  
Jonathan Weller ◽  
Sophie Katzendobler ◽  
Philipp Karschnia ◽  
Stefanie Lietke ◽  
Rupert Egensperger ◽  
...  

Abstract Introduction The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy. Methods Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed. Results PFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS. Conclusions PCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.



Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.



2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  

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]



Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4997
Author(s):  
Madelon Dijkstra ◽  
Sanne Nieuwenhuizen ◽  
Robbert S. Puijk ◽  
Florentine E. F. Timmer ◽  
Bart Geboers ◽  
...  

This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan–Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher’s exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts (p = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities (p = 0.010) and primary tumor location (p = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416–1.691; p = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249–1.756; p = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483–1.318; p = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).



2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shuo Li ◽  
Xiang-Yu Meng ◽  
Souraka Tapara Dramani Maman ◽  
Yong-Nong Xiao ◽  
Sheng Li

Background. Refractory and relapsed multiple myeloma (RRMM) remains a clinical challenge. We compared the progression-free survival (PFS) of RRMM patients treated with lenalidomide and low dose dexamethasone plus elotuzumab or carfilzomib (ELD vs. CLD), using reconstructed individual patient data (IPD) based on two published trials reports. Methods. We extracted data of study-level characteristics from original trial reports. We evaluated the comparability between the two treatment groups in terms of baseline status. Digitization of PFS Kaplan-Meier curves, reconstruction of IPD data, and subsequent survival analysis were performed. Distribution of progression and death events over time was visualized as histograms and corresponding kernel density lines, and Kaplan-Meier survival curves were plotted. Hazard ratio (HR) and corresponding 95% confidence interval (95% CI) were calculated. Results. Significant difference in race and disease stage distribution was found (P < 0.0001). Higher proportion of white patients and patients with advanced disease in the carfilzomib group was identified. Survival analysis revealed better PFS in the carfilzomib group (elotuzumab group vs. carfilzomib group: HR = 1.36, 95% CI = [1.11-1.67]). Conclusion. The CLD regimen may result in better PFS as compared with the ELD regimen in RRMM patients.



2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi75-vi76
Author(s):  
Catherine Garcia ◽  
Zin Myint ◽  
Rani Jayswal ◽  
Allison Butts ◽  
Heidi Weiss ◽  
...  

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.



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