Feasibility of metastasectomy in patients treated with bevacizumab in first-line mCRC - Preliminary results from the First Beat-study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3523-3523 ◽  
Author(s):  
M. Michael ◽  
E. Vancutsem ◽  
A. Kretzschmar ◽  
S. Berry ◽  
F. Rivera ◽  
...  
Keyword(s):  
Wound Healing ◽  
Residual Disease ◽  
Elective Surgery ◽  
Myocardial Infarct ◽  
Phase Iii ◽  
Major Surgery ◽  
Limited Data ◽  
First Line ◽  
Complete Wound Healing

3523 Background: In a phase III pivotal trial in patients (pts) with mCRC, bevacizumab (BEV) increased overall survival by 30% when added to first-line irinotecan, 5FU and leucovorin. The study reported 10% of pts having wound healing complications after major unplanned or elective surgery. The study had limited data on the feasibility and safety of metastastasectomies. First BEAT was opened to evaluate safety events of BEV in a broader pt population using a variety of chemotherapy (CT) regimens. Methods: First BEAT started in June 2004 and aims to enrol up to 2000 mCRC pts in 41 countries. Eligible patients starting with first-line CT are treated until progression with BEV (5mg/kg q2w (5FU based CT) or 7.5mg/kg q3w (Capecitabine (CAP) based CT). In case of major elective surgery, BEV should be stopped 6–8 weeks prior to the planned surgery and could be restarted 28 days after surgery and complete wound healing. At protocol visits, bleeding and wound healing data was collected according to CTC AE grading (v3.0). Results: By Dec 20th, 2005, 31 pts (13 male; median age 55 years; PS 0/1 90%/10%) had undergone metastasectomies. 27 were liver (1 pt had two operations), 3 lung, 1 peritoneal and 1 other resections. 27 were curative, 3 palliative and 2 other resections. 17 reported no residual disease, 5 had residual disease and for 8 resections the outcome was missing or unknown. Median time from first BEV treatment to surgery was 167 days and 54 days from last BEV administration to surgery, respectively. Median follow-up was 12.4 months. One pt died due to disease progression 5.5 months after surgery. CT regimens used with BEV included FOLFOX (N=9), CAPOX (N=9) and FOLFIRI (N=7). No wound healing or bleeding were reported. 21/31 pts reported no complications at all, for 3/31 data was currently missing and 7/31 pts reported the following complications: stomach perforation, right pleural effusion, surgical area infection, thrombosis portal vein/myocardial infarct, bowel-obstruction, ascites, ileus/cornea infection. Updated data will be available in June 06. Conclusions: Preliminary data suggest metastasectomies are feasible after treatment with BEV and CT. Stopping BEV 6–8 weeks before major surgery resulted in no bleeding or wound healing complications. [Table: see text]

scholarly journals Using a 4K three-dimensional exoscope system (Vitom 3D) for mastoid surgery during the coronavirus disease 2019 pandemic

2021 ◽  
pp. 1-3
Author(s):  
M Ally ◽  
P Kullar ◽  
G Mochloulis ◽  
A Vijendren
Keyword(s):  
Residual Disease ◽  
Elective Surgery ◽  
Three Dimensional ◽  
Depth Of Field ◽  
High Definition ◽  
Microscopic Surgery ◽  
Lateral Skull Base ◽  
Mastoid Surgery ◽  
And Training

Abstract Objective Microscopic surgery is currently considered the ‘gold standard’ for middle-ear, mastoid and lateral skull base surgery. The coronavirus disease 2019 pandemic has made microscopic surgery more challenging to perform. This work aimed to demonstrate the feasibility of the Vitom 3D system, which integrates a high-definition (4K) view and three-dimensional technology for ear surgery, within the context of the pandemic. Method Combined approach tympanoplasty and ossiculoplasty were performed for cholesteatoma using the Vitom 3D system exclusively. Results Surgery was performed successfully. The patient made a good recovery, with no evidence of residual disease at follow up. The compact system has excellent depth of field, magnification and colour. It enables ergonomic work, improved work flow, and is ideal for teaching and training. Conclusion The Vitom 3D system is considered a revolutionary alternative to microscope-assisted surgery, particularly in light of coronavirus disease 2019. It allows delivery of safe otological surgery, which may aid in continuing elective surgery.

Tailored immunotherapy approach with nivolumab in advanced transitional cell carcinoma (TITAN-TCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 446-446
Author(s):  
Marc-Oliver Grimm ◽  
Bernd Schmitz-Dräger ◽  
Uwe Zimmermann ◽  
Barbara Grün ◽  
Gustavo Bruno Baretton ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Transitional Cell ◽  
Added Value ◽  
Phase Iii ◽  
First Line ◽  
Third Line

446 Background: Several PD-1 immune-checkpoint inhibitors including Nivolumab (Nivo) are approved in urothelial cancer. Recently, in the front line setting, improved activity of combined PD-L1 and CTLA4 immune-checkpoint inhibition has been reported and a phase III trial with Nivolumab + Ipilimumab (Nivo+Ipi) is ongoing. Here we report a response-based tailored approach starting treatment with Nivo monotherapy using Nivo+Ipi as immunotherapeutic “boost”. Methods: Between July 2017 and April 2019 86 patients were enrolled and treated according to protocol version 3 (cohort 1). Patients started with Nivo 240 mg Q2W induction. After 4 dosings and tumor assessment at week 8 (i) responders (PR/CR) to Nivo monotherapy continued with maintenance while (ii) patients with stable (SD) or progressive disease (PD) received 2 cycles Nivo3+Ipi1 followed by another 2 cycles Nivo1+Ipi3 if not responding. Median follow-up is 8.7 months. The primary endpoint is confirmed investigator-assessed objective response rate (ORR) per RECIST1.1. Secondary endpoints include activity of Nivo monotherapy at week 8, remission rate with Nivo+Ipi “boosts”, safety, overall survival and quality of life. Results: Of the patients 42, 39 and 5 were first, second and third line, respectively. Median age was 67 years (range 45-84), 61 patients (71 %) were male and 25 female. ORR with Nivo monotherapy at first assessment (week 8) was 29 % and 23 % in first and second/third line, respectively. Of the patients 41 received Nivo+Ipi “boosts” after week 8 while 12 received later “boosts”. Best overall response (BOR) rate with Nivo induction ± Nivo+Ipi “boosts” was 48 % and 27 % in first and second/third line, respectively. In first line 7/17 (41 %) patients receiving Nivo+Ipi after week 8 had an improved response compared to 2/24 (8.3 %) in second/third line. Of the patients who continued with Nivo maintenance after week 8 and received later “boosts” 2/12 (17 %) had a PR and 2/12 (17 %) improved to SD. Treatment-related AEs will be presented. Conclusions: TITAN–TCC explores a response-driven use of Nivo+Ipi as an immunotherapeutic “boost”. In first line, this significantly improved ORR compared to the expected response rate of Nivo monotherapy, providing further evidence to the added value of Ipi in combination with Nivo. Further follow-up is ongoing to characterize duration and depth of response. Clinical trial information: NCT03219775 . Research Sponsor: Bristol-Myers Squibb[Table: see text]

scholarly journals Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner
Keyword(s):  
Systemic Treatment ◽  
Sequential Treatment ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Curative Surgery ◽  
To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6032-6032
Author(s):  
Wang Fang FangZheng
Keyword(s):  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Long Term Outcomes ◽  
First Line ◽  
Grade 3

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P > 0.05) and 97.8% (P > 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.

scholarly journals ATIM-13. MULTIMODAL IMMUNOTHERAPY WITH IO-VAC® FOR PATIENTS WITH GBM: A SINGLE INSTITUTION EXPERIENCE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi4-vi4
Author(s):  
Stefaan Van Gool ◽  
Jennifer Makalowski ◽  
Wilfried Stuecker
Keyword(s):  
Tumor Antigens ◽  
Residual Disease ◽  
Local Therapy ◽  
Autologous Tumor ◽  
Line Treatment ◽  
First Line ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy ◽  
First Line Treatment

Abstract Multimodal immunotherapy (Newcastle Disease Virus (NDV) + modulated electrohyperthermia + IO-VAC® + immunomodulatory strategies) is an innovative treatment for primary GBM and might prolong overall survival (OS). IO-VAC® consists of DCs loaded with autologous tumor antigens and matured with cytokine cocktail and NDV. We retrospectively reviewed 132 cases of primary GBM. Multimodal immunotherapy was integrated as individualized treatment approach and following different scenario’s in combination with standard treatment in the first line treatment in 71 patients, used at time of first or subsequent relapse as treatment with or without chemotherapy in 61 cases. Median ages were resp. 55 and 53 y. Median KPI at start of immunotherapy was 90 and 80. Median OS for the patients treated with immunotherapy as part of first-line treatment was 20 months with 2-y OS of 40% (CI95%: -13,+13). Median OS for patients treated at time of relapse was 7 months with but still with 18-m OS of 16% (CI95%: -12,+9). Two resp. 1 patients were lost of follow up. A subgroup of 34 GBM patients (10 females) with median age 58y (20–67) was detected, who received NDV + modulated electrohyperthermia during Temozolomide maintenance cycles followed by two IO-VAC® DC vaccinations, and further NDV + modulated electrohyperthermia courses. Median KPI was 70 (60–100). MGMT status was methylated (12), unmethylated (13), unknown (9). Median OS for this subgroup was 23.4 months with 2-year OS of 48% (CI95%: -18,+20). Immunotherapy was feasible without immunotherapy-related side effects of grade III or more. The data suggest that multimodal immunotherapy with IO-VAC® already during and after maintenance chemotherapy, at time of achieved minimal residual disease with local therapy, might help in prolongation of OS. Prolongation of OS in a small group of patients at time of relapse was also demonstrated. IO-VAC® is an approved advanced therapy medicinal product (DE-NW-04-GMP-2015-0030).

A pilot study of topotecan in the treatment of serous carcinoma of the uterus

2003 ◽  
Vol 13 (2) ◽  
pp. 216-222
Author(s):  
J. T. Chambers ◽  
T. J. Rutherford ◽  
P. E. Schwartz ◽  
M. L. Carcangiu ◽  
S. K. Chambers ◽  
...  
Keyword(s):  
Pilot Study ◽  
Topoisomerase I ◽  
Residual Disease ◽  
Serous Carcinoma ◽  
Hematologic Toxicity ◽  
First Line ◽  
Uterine Serous Carcinoma ◽  
Grade 3 ◽  
Disease Free

A pilot study investigated topotecan (Hycamtin, GlaxoSmithKline, Philadelphia, PA), a topoisomerase I inhibitor, in treating uterine serous carcinoma, a typically unresponsive aggressive tumor. Fifteen patients were surgically staged, then treated with topotecan (1.5 mg/m2, Days 1–5 every 21 days) as first-line therapy (n = 12) or secondary to platinum failure (n = 3). Patients received topotecan through six courses, disease progression, or unacceptable toxicity. Grade 3/4 hematologic toxicity prompted dose adjustments. Thirteen patients exhibited no gross evidence of residual disease postoperatively. At topotecan initiation, one patient had 5-cm and one had < 1-cm residual disease. Seventy-eight courses (median, six) were administered; 12 (80%) patients completed the specified protocol. Common serious toxicities included grade 3 neutropenia (33%), anemia (13%), and thrombocytopenia (13%). Eight patients received erythropoietin and/or granulocyte colony-stimulating factor. Median follow-up for 14 evaluable patients was 26 months (range, 13–40). Of 11 evaluable first-line topotecan patients, nine were alive at follow-up; five were disease-free. Of three second-line topotecan patients, two died and one was alive with disease 31 months post-treatment. One patient with measurable disease achieved a complete and one a partial response as assessed by computed tomography scan. Median progression-free survival was 25 months; median survival has not been reached at 26 months. Although topotecan's antitumor activity cannot yet be quantified, disease-free interval and survival outcomes compare favorably with other therapies in uterine serous carcinoma. Further evaluation of topotecan in this population is warranted.

90Yttrium-Ibritumomab-Tiuxetan as First-Line Treatment for Follicular Lymphoma: 30 Months of Follow-Up Data From an International Multicenter Phase II Clinical Trial

2013 ◽  
Vol 31 (3) ◽  
pp. 308-313 ◽  
Author(s):  
Christian W. Scholz ◽  
Antonello Pinto ◽  
Werner Linkesch ◽  
Ola Lindén ◽  
Andreas Viardot ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Residual Disease ◽  
Standard Procedure ◽  
Complete Response ◽  
Molecular Response ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Multicenter Phase

Purpose We report on a multicenter phase II trial of 90yttrium-ibritumomab-tiuxetan (90YIT) as first-line stand-alone therapy for patients with follicular lymphoma (FL). Patients and Methods Fifty-nine patients with CD20+ FL grade 1 to 3a in stages II, III, or IV, age 50 years old or older requiring therapy were enrolled. They received 90YIT according to standard procedure. If complete response (CR) or unconfirmed complete response (CRu) without evidence for minimal residual disease (MRD) 6 months after application of 90YIT was achieved, patients were observed without further intervention. The same applied to patients with partial response (PR) or with stable disease (SD). Patients with CR but with persisting MRD were to receive a consolidation treatment with rituximab. Primary end point was the clinical and molecular response rate. Secondary end points were time to progression, safety, and tolerability. Results Six months after treatment with 90YIT, 56% of the patients showed a CR or CRu and 31% achieved a PR. After a median follow-up of 30.6 months, the progression-free survival (PFS) was 26 months. There was a trend for shorter PFS in patients with increased lactate dehydrogenase (LDH). Of the 26 patients who had CR 12 months after 90YIT, only three had relapsed. Median time to next treatment has not been reached. The most common toxicities were transient thrombocytopenia and leukocytopenia. Nonhematologic toxicities never exceeded grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE v2.0). Conclusion 90YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after 90YIT appear to have long- lasting responses.

Mabthera (Rituximab) Plus CVP Chemotherapy for First-Line Treatment of Stage III/IV Follicular Non-Hodgkin’s Lymphoma (NHL): Confirmed Efficacy with Longer Follow-Up.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 350-350 ◽  
Author(s):  
Philippe Solal-Celigny ◽  
Kevin Imrie ◽  
Andrew Belch ◽  
Katherine Sue Robinson ◽  
David Cunningham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Progression ◽  
Phase Iii ◽  
Stage Iii ◽  
Line Treatment ◽  
First Line ◽  
Time To Death ◽  
Kaplan Meier ◽  
First Line Treatment

Abstract Design/Methods: We recently demonstrated in a phase III trial that the addition of rituximab to each of 8 cycles of CVP (R-CVP) chemotherapy significantly improves the clinical outcome of previously untreated patients with stage III/IV CD20 positive follicular NHL when compared to CVP alone (Marcus et al., Blood2005; 105: 1417–23). A multivariate Cox regression analysis of time to progression or death (TTP) showed a treatment benefit in all patient subgroups according to baseline risk factors, except for patients with a baseline hemoglobin level below normal. We now present an updated analysis of all major trial endpoints with 42 months follow-up (FU). Results: A total of 321 patients (median age 53 years) were recruited (159 CVP, 162 R-CVP). Approximately half of the patients had high-risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI, score 3–5). The median TTP was more than doubled for patients receiving R-CVP compared to CVP alone (33.6 months vs 14.5 months, p&lt;0.0001). Median time to new lymphoma treatment or death (TNLT) was 12.3 months in the CVP group and nearly quadrupled to 46.3 months in the R-CVP group (p&lt;0.0001). Superior response rates for R-CVP were confirmed (CR+CRu rate 41% vs 11%, p&lt;0.0001) with a median response duration (DR) of 13.5 months in the CVP arm versus 37.7 months in the R-CVP arm. Median disease free survival (DFS) in complete responders was 44.8 months for patients receiving R-CVP and 20.5 months in patients receiving CVP alone (p=0.0005). Thirty-five patients in the CVP arm and 23 patients in the R-CVP arm have died. Kaplan-Meier estimates of 3-year OS rates were 81% in the CVP arm and 89% in the R-CVP (p=0.07). Importantly, significantly more patients receiving CVP died due to lymphoma progression compared to patients receiving R-CVP (25 vs 12 deaths, p=0.02). Subgroup analysis for TTP, ORR, DR and OS according to risk factors at baseline are ongoing and will be presented. Conclusion: With longer FU, the combination of 8 cycles of rituximab with CVP chemotherapy continues to provide a major benefit as first line treatment for patients with advanced stage follicular NHL. Kaplan Meier plot of time to death due to disease progression Kaplan Meier plot of time to death due to disease progression

Reduced Intensity Stem Cell Transplantation and Donor Lymphocyte Infusion after Imatinib Induction To Eradicate Residual Disease in Chronic Myeloid Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1097-1097
Author(s):  
Nicholas Heaney ◽  
Mhairi Copland ◽  
Karen Stewart ◽  
Judith Godden ◽  
Anne Parker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Control ◽  
Cell Transplantation ◽  
Residual Disease ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Reduced Intensity

Abstract Recommended first-line therapy for patients with chronic phase (CP) CML is imatinib mesylate (IM). Although IM induces complete cytogenetic responses (CCR) in the majority of patients, disease often remains detectable by Q-RT-PCR, likely reflecting stem cell persistence. Furthermore, primary and acquired resistance to IM have led to concerns about response durability. Allogeneic stem cell transplantation (SCT) remains the only curative option and with reduced intensity conditioning (RISCT) is less toxic and may be offered to a broader patient group. Our novel approach used IM to establish disease control (CCR) in patients with newly diagnosed CP CML prior to RISCT (fludarabine/melphalan/MabCampath). Prophylactic escalating DLI was given for residual disease. 18 patients (4 centres) were recruited between 2001 and 2006. Of these, 3 received myeloablative SCT, 2 for progression to blast crisis prior to SCT and the third for failing to reach a major cytogenetic response. 15 patients with a median age of 39y (21–56y) received sibling RISCT. Hasford scores were 38% low, 54% intermediate and 8% high risk. EBMT risk scores were 1–2 (13 patients) and 3–4 (2 patients). 5 patients required IM dose escalation to achieve CCR prior to RISCT. Follow-up data extends to a median of 31 (12–61) months (m) post RISCT. The RISCT procedure was well tolerated with rapid engraftment and short in-patient stays. 53% had infective episodes post RISCT, including CMV reactivation (86% patients at risk), EBV+ post transplant lymphoproliferative disease (2 patients) and PCP (1 patient). 1 patient developed aGvHD (grade III) and 8 cGvHD (6 limited, 2 extensive). DLI was given to 13 patients (87%), 6 for elevated Bcr-Abl, 4 for mixed chimerism and 2 for both. The median total dose was 0.65 × 107CD3+cells/kg (0.1–6.65 × 107cells/kg) in a median of 2 infusions. GvHD was seen in 6 of 12 patients receiving DLI (50%). IM was required in 4 patients with residual disease and all discontinued IM once disease control was re-established (4–13m of IM). 1 of 15 transplanted has died (at 12m with GvHD and infection). Of surviving patients median Bcr-Abl measurements fell as follow-up progressed. 8 patients currently have sustained undetectable Bcr-Abl. 7 of these 8 received DLI, the other had GvHD. The interval between last DLI and first proof of disease eradication was median 2m (range 1–28m). Only 2 of these 8 patients received IM post-transplant. In this study, the patients receiving RISCT were in early CP with a CCR to IM. It is likely that the majority would have maintained CCR if not offered transplantation. However the number of patients who achieved undetectable Bcr-Abl following RISCT and DLI compares favourably with the response expected with IM alone. The patients have tolerated the transplant procedure well and are currently off all treatment for CML. Regular monitoring remains necessary, however if relapse occurs it should be DLI responsive. Currently IM is the accepted first line therapy in the majority of patients however we would highlight the importance of RISCT in selected groups and believe our approach is effective and well tolerated.

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