P14.92 Combination of Tumor Treating Fields and CCNU chemotherapy as valuable option for the treatment of unresectable progressive glioblastoma: A case presentation

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii55-ii55
Author(s):  
E Mergen ◽  
S Landrock ◽  
B Chizzali
Keyword(s):  
Combination Therapy ◽  
Right Hemisphere ◽  
Occipital Region ◽  
Second Line ◽  
Second Line Therapy ◽  
Term Survival ◽  
Tumor Treating Fields ◽  
Line Therapy ◽  
Perifocal Edema ◽  
The Right

Abstract BACKGROUND Tumor Treating Fields (TTFields) are low intensity (1–3 V/cm) alternating electric fields with an intermediate frequency of 100–300 kHz. TTFields in addition to temozolomide (TMZ) after radiochemotherapy according to Stupp significantly increased progression-free survival (PFS), overall survival (OS) and long-term survival rates in patients with newly diagnosed glioblastoma (GBM) in the multicenter phase 3, EF-14 trial. Post-hoc analysis of the trial revealed that TTFields in combination with second-line therapy after first recurrence significantly prolonged OS compared to second-line therapy alone. We here report on a GBM patient with partial resection showing regressive volume of unresected, previously progressive tumor under combination therapy of TTFields and second-line CCNU chemotherapy. MATERIAL AND METHODS In November 2018, MRI of a 59-year-old female patient revealed a large heterogeneous space-occupying lesion in the left occipital region with clearly contrast-enhanced margin, perifocal edema and two smaller contrast-enhancing lesions in the splenium corporis callosi and right of the trigonum suboccipitale. While the tumor in the left occipital region was completely resected, lesions in the right hemisphere remained unresected. Histopathology identified MGMT-promoter methylated GBM. The patient received concomitant radiochemotherapy followed by adjuvant TMZ. However, after three cycles, the unresected tumor progressed, TMZ was exchanged by procarbazine/CCNU and TTFields therapy was initiated. After two cycles, chemotherapy was changed to only CCNU due to further progression while TTFields therapy was continued. RESULTS One year after diagnosis, MRI showed no contrast-enhancing tissue in the resection cavity and regressive perifocal edema while lesions in the right hemisphere remained stable. Under tolerable hematotoxicity CCNU was continued together with TTFields, to which the patient showed high adherence far beyond the suggested threshold of 75%. Control examination in February 2020 reported regressive tumor volume in the right hemisphere under CCNU/TTFields therapy. Until January 2021, the tumor regressed even further without the detection of new lesions. The patient is currently continuing CCNU together with TTFields, achieving an average usage of 84% over the last twelve months. CONCLUSION In the presented case, the combination of TTFields and CCNU was feasible and safe in progressive GBM. The patient showed radiological response and local tumor regression under the combination therapy, whereas the tumor had previously progressed under chemotherapy alone. In conclusion, the addition of TTFields to chemotherapy is a valuable treatment option to improve clinical and radiological outcome of patients with progressive GBM. This example of TTFields use in clinical practice encourages its use beyond tumor progression.

Combination therapy of low-dose gemcitabine and paclitaxel in every 4 weeks for patients with platinum-resistant urothelial cancer whose performance status is 2 or 3.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 462-462
Author(s):  
Tomohiro Matsuo ◽  
Yasuyoshi Miyata ◽  
Yuji Sagara ◽  
Kojiro Ohba ◽  
Hideki Sakai
Keyword(s):  
Combination Therapy ◽  
Urothelial Cancer ◽  
Low Dose ◽  
Performance Status ◽  
Control Group ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
Experimental Group

462 Background: Platinum-based regimens are standard therapy for advanced urothelial cancer (UC). However, second-line chemotherapy is still not established. Therefore, best supportive care is often selected in patients with poor performance status (PS). In our hospital, combination therapy of low-dose gemcitabine and paclitaxel every 4 weeks is administered as second-line therapy for platinum-resistant patients with PS 2 or 3. We investigated the quality of life (QoL) and safety of our regimen in these patients. Methods: Forty-two advanced UC patients were treated with gemcitabine (700 mg/m2 on day 1) and paclitaxel (70 mg/m2 on day 1) every 4 weeks (experimental group). The QoL was evaluated using the short-form survey (SF)-36, and the data were collected on the day before the first cycle was started and 8 weeks after starting the therapy. In addition, survival analysis was performed between these patients and 30 patients who received no second-line therapy (control group). Results: In experimental group, one patient showed grade 3 anemia after the treatment. However, this patient also had severe hematuria before staring of the therapy. No patient had severe adverse events (grade 3 and higher) because of this therapy. The QoL score decreased after the therapy; however, the difference was not significant. With regard to efficacy, partial response was found in two patients, and the mean/SD survival period of the experimental group was 9.2/7.2 months. This period was significantly (P < 0.01) longer than that in the control group (5.8/2.4 months). In addition, 13 (31.0%) and 6 patients (14.3%) survived over 12 and 18 months, respectively. Conclusions: Combined therapy of low-dose gemcitabine and paclitaxel every 4 weeks was well tolerated, and the patient’s QoL was maintained after treatment. Some patients showed relatively long survival periods. We suggest that this treatment regimen is worthy of consideration as second-line therapy for patients with advanced UC with PS 2 or 3.

Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel with or without bevacizumab as second-line therapy or beyond for patients with metastatic non-small-cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20517-e20517
Author(s):  
Fan Zhang ◽  
Tao Li ◽  
Yuzi Zhang ◽  
Shangli Cai ◽  
Lei Zhao ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Therapy Group ◽  
Group Versus ◽  
Combination Therapy Group ◽  
Second Line ◽  
Monotherapy Group ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients

e20517 Background: Immunotherapy combined with platinum-based chemotherapy is now standard first line treatment for NSCLC patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Therefore, a retrospective study was conducted to assess whether immunotherapy plus nab-paclitaxel with or without bevacizumb could improve efficacy compared with immune monotherapy as second line therapy or beyond for NSCLC patients. Methods: Patients with metastatic NSCLC receiving anti-PD-1/PD-L1 monotherapy or combination therapy from 2015 to 2018 were identified in Chinese People’s Liberation Army General Hospital. Patients who received PD-1/PD-L1 inhibitors as first-line therapy or combined with therapies other than nab-paclitaxel and bevacizumab were excluded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR) and safety. Results: Of 59 patients, 42 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel with or without bevacizumab. With a median follow-up of 8.2 months, combination therapy group showed significantly longer PFS compared with monotherapy group (8.4m vs. 3.7m, P = 0.047). When adjusted by covariates in COX proportional regression model, both treatment group (P = 0.007, Hazard ration [HR] 0.32; 95%CI 0.14-0.73) and performance status (P = 0.018, HR 0.44; 95%CI 0.22-0.87) demonstrated significant contribution to longer PFS. In addition, ORR was 23.5% (4/17) in the combination therapy group versus 12.8% (5/39) in the monotherapy group (P = 0.265) and the DCR was 88.2% (15/17) in the combination therapy group versus 61.5% (24/39) in the monotherapy group (P = 0.061). The incidence of grade 3/4 adverse events were 23.5% (4/17) in the combination therapy group and 4.8% (2/42) in monotherapy group (P = 0.052). Conclusions: PD-1/PD-L1 inhibitor plus nab-paclitaxel with or without bevacizumab resulted in significantly longer PFS and higher DCR as second line therapy of beyond in metastatic NSCLC patients. These findings need to be further explored by randomized controlled studies.

scholarly journals Tigecycline as a Second-Line Agent for Legionnaires’ Disease in Severely Ill Patients

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Deepika Slawek ◽  
Diana Altshuler ◽  
Yanina Dubrovskaya ◽  
Eddie Louie
Keyword(s):  
Combination Therapy ◽  
Clinical Response ◽  
Second Line ◽  
Cell Models ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Clinical Challenge ◽  
Immunosuppressed Patients ◽  
Legionnaires Disease ◽  
High Concentrations

Abstract Treatment of Legionnaires’ disease in severely ill or immunosuppressed patients presents a clinical challenge. Tigecycline (TG) achieves high concentrations intracellularly and has been shown to be effective against L. pneumophila in animal and cell models. We report our experience using TG as second-line therapy. Clinical response was seen in most patients after switching to TG alone or as a combination therapy.

scholarly journals BCR-ABL1 Transcript of 7.93% at 3 Months Is an Early Predictor for Long-Term Survival to Second-Line Therapy Using Next Generation Tyrosine Kinase Inhibitors in Imatinib-Resistant Chronic Phase Chronic Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4564-4564
Author(s):  
Sung-Eun Lee ◽  
Soo Young Choi ◽  
Yun Jeong Oh ◽  
Soo-Hyun Kim ◽  
Hye-Young Song ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Independent Predictor ◽  
Chronic Phase ◽  
Third Generation ◽  
Second Line ◽  
Second Line Therapy ◽  
Term Survival ◽  
Long Term Survival ◽  
Line Therapy

Abstract Abstract Background: The first BCR-ABL1 tyrosine kinase inhibitor (TKI), imatinibmesylate (IM), has become a first-line therapy for chronic phase (CP) chronic myeloid leukemia (CML). However, approximately one third of IM-treated patients discontinue therapy due to an inadequate response or adverse event. More potent second or third generation TKIs such as nilotinib, dasatinib, radotinib, bosutinib and ponatinib have developed and these agents have shown high rates of hematologic and cytogenetic responses after failure of IM therapy. Although the new European Leukemia Net (ELN) recommendation serves provisionally the definitions of the response to second-line therapy, early molecular milestones which are associated with the best long-term are not confirmed. The aim of this study was to identify 3-month molecular milestone for predicting long-term survival to second-line therapy using second or third generation TKIs in CP CML patients who showed a failure or warning to IM. Methods: Between March 2005 and January 2014, 198 CP CML patients with failure or warning to IM (defined by 2013 ELN recommendation) had been treated with nilotinib, dasatinib, radotinib, bosutinib or ponatinib as a second-line therapy. Among them, 180 patients had available molecular data at 3 months from the initiation of second-line therapy. Based on receiver operating characteristic (ROC) curveanalysis, the predictive cutoffs of BCL-ABL1 transcripts at 3 months for progression-free survival (PFS), and overall survival (OS) were evaluated. OS included any death regardless of causes, and PFS included progression to AP or BP as well as death resulting from any reason. OS and PFS were also collected on patients who were treated with other TKIs after failure of second-line TKI therapy. Results: A total of 180 patients were treated with second-line TKI, dasatinib (n=66), nilotinib (n=61), radotinib (n=44), bosutinib (n=7), and ponatinib (n=2). 119 men and 61 women were included and their median age was 42 years (range, 15-75). Using a ROC curve analysis, BCR-ABL1 transcript level 7.93% on the international scale, at 3 months were predictive cutoffs for both PFS and OS. The median follow-up for survivors since the start of second-line TKI was 78.73 months (range, 6.3-114.0 months). 104 patients continue on therapy and 76 patients were permanently discontinued due to intolerance (n=38), failure (n=20), progression (n=14), and others (n=4). The7-year PFS and OS were 82.6% and 85.3%, respectively. The patients with transcript levels below 7.93% at 3 months had significantly better 7-year PFS (95.1% vs. 60.4%; P < 0.001) and OS (96.3% vs. 67.9%; P < 0.001). After adjusting for potential factors affecting PFS and OS in univariate analyses, multivariate analyses showed that BCR-ABL1 transcript of 7.93% at 3 months was the independent predictor for PFS (RR of 8.37, P < 0.001) and OS (RR of 13.53, P = 0.001). In addition, increasing age (RR of 1.05, P = 0.023) and presence of BCR-ABL1 kinase domain abnormalities (KDA) at baseline (RR of 5.83, P = 0.007) were associated with a lower OS. Conclusions: Our data showed BCR-ABL1 transcript of 7.93% at 3 months was an early independent predictor for long-term survival to second-line TKIs in IM-resistant CP CML. It implies that the patients who failed an achievement of reduction of BCR-ABL1transcripts to this level may require more precise monitoring on second-line therapy, allowing early clinical intervention using other third-line TKI therapy or allografting. Disclosures No relevant conflicts of interest to declare.

Long-Term Continuing Second Complete Remission (CCR2) despite Allogeneic Stem Cell Transplantation in CR1: Results from the International Randomised Phase III Study Pediatric Relapsed AML 2001/01

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2977-2977
Author(s):  
G.J.L. Kaspers ◽  
M. Zimmermann ◽  
D. Reinhardt ◽  
B. Gibson ◽  
R. Tamminga ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Late Relapse ◽  
Second Line ◽  
Second Line Therapy ◽  
Term Survival ◽  
Probability Of Survival ◽  
Line Therapy

Abstract Relapse remains the commonest adverse event in newly diagnosed AML patients, and the reported long-term survival after relapse in pediatric AML is 20–30%. Allogeneic stem cell transplantation (allo-SCT) in CR1 is employed by several groups with the aim of reducing the relapse rate. There is a widely held view that patients with AML who relapse after an allo-SCT in CR1 have no or minimal chances of long-term survival. However, such a cohort has never been described in the literature. Therefore, the outcome of children with AML who received an allo-SCT in CR1 and who subsequently relapsed and were enrolled in study Relapsed AML 2001/01 is described. This is a prospective, randomised study for relapsed AML, excluding AML M3 and those &gt;18 years of age at initial diagnosis comparing FLAG with Daunoxome-FLAG. FLAG is given for 2 consecutive courses: fludarabine 30 mg/m2/day × 5 days, cytarabine 2 g/m2/day × 5 days, G-CSF 200 μg/m2/dose × 6 days, starting day −1. Liposomal daunorubicin (DaunoXome®, DNX; a new anthracycline with potentially less cardiotoxicity) at 60 mg/m2/day on days 1, 3 and 5 is added or not in a 1:1 randomised fashion to the first course of FLAG. After two courses, patients are eligible for allo-SCT, sometimes bridged by high-or low-intensity consolidation chemotherapy. Efficacy data for both arms are still blinded as the study remains open until the end of 2008. Thirteen groups worldwide are enrolling patients. More than 500 patients were registered by April 2008, but this analysis relates to 329 fully evaluable patients diagnosed before July 2007, who are known to have or have not received an allo-SCT in CR1. Reasons for allo-SCT in CR1 differ between groups, but in general it is reserved for higher-risk patients and predominantly those with a matched-sibling donor. As part of relapsed treatment, 214 patients underwent allo-SCT to consolidate second line therapy, and for 11 patients this was their second allo-transplant. Twenty-two (7%) of these 329 patients had undergone allo-SCT in CR1, 12 boys and 10 girls, the majority being between 1 and 10 years of age. Three out of these 22 patients had a favorable karyotype, i.e. inv(16) or t(8;21). The majority of these patients (17/22, 77%) had a late relapse (occurring at least one year from initial diagnosis) compared to 47% of relapsed AML patients who had not received an allo-SCT in CR1 (p=0.01). There was no significant difference in chemotherapy related morbidity or mortality between those children who had received an allo-SCT in CR1 and those who had not, including cardiotoxicity. The percentage of so-called poor early responders (more than 20% bone marrow blasts on day “28” sampled shortly before the 2nd reinduction course) was 24% versus 23% (n.s.) and the CR2 rate 45% versus 65% (p=0.09) in the yes and no allo-SCT in CR1 patients, respectively. Within late relapsed AML only, the rate of poor early responders was 23% versus 15% (n.s.) and the CR2 rate 50% versus 77% (p=0.03) in the yes and no allo-SCT in CR1 patients, respectively. Finally, 4-year probability of survival from relapsed AML was 27% (95%-C.I. 8–47%) in the “yes allo-SCT in CR1” subgroup compared to 33% (27–39%) in the remaining patients (n.s.). Limiting this analysis to late relapsed AML patients, it was 29% (6–53%) versus 45% (36–54), respectively (n.s.). Five of the 6 patients who survived after allo-SCT in CR1 (median follow up 2 years) received a second allo-SCT. In conclusion, the small number of trial patients who relapsed early and who had received an allo-SCT in CR1 suggests that clinicians may have been reluctant to enter these patients into trial. In general, patients with an early relapse of AML treated in this study have a reasonable chance of cure (Kaspers et al., ASH 2007 and 2008), but the very small number of such patients who had an allo-SCT in CR1 preclude any firm conclusions for that subgroup. Patients with a late relapse who have received an allo-SCT in CR1 appear to have a somewhat (but statistically not significant) inferior outcome compared to patients who were not transplanted in CR1. The probability of survival at 4 years from relapse of nearly 30% warrants the use of second line therapy in patients with a late relapse despite allo-SCT in CR1.

scholarly journals Treatment of Advanced or Recurrent Endometrial Carcinoma With Doxorubicin in Patients Progressing After Paclitaxel/Carboplatin: Memorial Sloan-Kettering Cancer Center Experience From 1995 to 2009

2013 ◽  
Vol 23 (5) ◽  
pp. 929-934 ◽  
Author(s):  
Vicky Makker ◽  
Martee L. Hensley ◽  
Qin Zhou ◽  
Alexia Iasonos ◽  
Carol. A. Aghajanian
Keyword(s):  
Overall Survival ◽  
Endometrial Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Second Line ◽  
Survival Times ◽  
Second Line Therapy ◽  
Term Survival ◽  
Line Therapy

ObjectiveLong-term survival for patients with advanced endometrial carcinoma is poor, and limited options exist for the management of recurrent disease. Our goal was to investigate the activity of doxorubicin in the second-line setting in patients who progressed after paclitaxel/carboplatin adjuvant treatment.MethodsWe conducted a retrospective analysis of patients with recurrent endometrial carcinoma who were treated at Memorial Sloan-Kettering Cancer Center from 1995 to 2009 and who received paclitaxel/carboplatin adjuvant chemotherapy followed by second-line doxorubicin therapy at time of recurrence. The median progression-free survival (PFS) and overall survival times following paclitaxel/carboplatin and following second-line doxorubicin therapy were estimated using the Kaplan-Meier method. Toxicity was assessed by the treating physician at each visit and graded using version 4.0 of Common Terminology Criteria for Adverse Events. Patient presentation, treatment, patterns of recurrence, and patient outcomes were summarized.ResultsSeventeen patients were included in study analyses. The median PFS from completion of paclitaxel/carboplatin was 8.0 months (95% confidence interval [CI], 4.5–13.6 months). At the time of recurrence, all 17 patients were treated with doxorubicin as second-line therapy. No patient achieved objective response of stable disease. The median PFS of this cohort following doxorubicin treatment was 2.1 months (95% CI, 0.95–2.7) months. Median overall survival was 5.8 months (95% CI, 1.0–15.0 months). There is only 1 patient still alive; her median follow-up time is 49.4 months. Predominant doxorubicin-related grade 2 toxicities included nausea/vomiting (18.8%), fatigue (18.8%), and neutropenia (12.5%). No grade 3 or 4 toxicities occurred.ConclusionsAmong patients with advanced endometrial carcinoma who had received adjuvant paclitaxel/carboplatin, treatment with doxorubicin at time of disease recurrence failed to achieve any objective responses and was associated with a very short (2 months) time to progression. Doxorubicin may be considered inactive as second-line therapy in this endometrial carcinoma population.

Outcomes after first-line therapy for immune/immune or immune/VEGF combinations.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 706-706
Author(s):  
Francesca Jackson-Spence ◽  
Agne Jovaisaite ◽  
Michael Grant ◽  
Wing-Kin Liu ◽  
Thomas Butters ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Therapy ◽  
Response Rates ◽  
Second Line ◽  
Front Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Group I

706 Background: The introduction of first line immune combination or immune/VEGF therapy in metastatic renal cancer has changed treatment landscape. Here we compare outcomes of these combinations with patients treated with first line sunitinib. The focus is on the impact of subsequent treatments. Methods: This retrospective analysis was performed at Barts Cancer Institute for consecutive patients from April 2015 when front line immune therapy was first used at our institution. Only patients enrolled on reported prospective trials were included to avoid selection bias. Patients were treated with VEGF targeted therapy (n=35) (group V), PD-1 + CTLA4 (n=15) (group I/I) or a combination of PD-L1 + VEGF TKI inhibitor (n=29) (group I/V). The primary analysis focused on the proportion of patients who received second line therapy and their outcome. Results: 79 patients received first line therapy for clear cell RCC. IMDC good, intermediate and poor risk occurred in 27.8%, 60.8% and 11.4% respectively. Front line response rates for V, I/I and I/V groups were 34.3%, 46.7% and 65.5% and PFS in V, I/I and I/V groups were 11mo (95%CI 6-16), 18mo (95% CI 0-41) and 36mo (95% CI 13-59), respectively (P= 0.016). OS in the 3 groups were immature but not significantly different. Second line therapy occurred in 87.5%, 92.9% and 81.8% in the V, I/I and I/V groups respectively (in those who progressed after initial therapy). Second line response rate post first line V, I/I and I/V were 11%, 0% and 0% respectively as per RECIST 1.1. 63% of patients receiving VEGF front line therapy subsequently received immune therapy. 95% of patients receiving first line immune/immune or immune/VEGF combination therapy received VEGF therapy in the second line. Only 70% of patients who progressed on second line therapy got 3rd line therapy across all arms. Conclusions: Response rates after front line immune combination therapy are modest. The sequencing of PD-1 therapy after VEGF monotherapy appears particularly relevant in outcomes. A high proportion of patients are sequencing therapy and reaching third line which may help improve outcomes.

Sign in / Sign up

Export Citation Format

Share Document