Low-dose chemotherapy with methotrexate and vinblastine for patients with refractory desmoid tumors: A second report of relationship between efficacy and various factors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11050-11050
Author(s):  
Yoshihiro Nishida ◽  
Tomohisa Sakai ◽  
Koki Shimizu ◽  
Hiroshi Urakawa ◽  
Eisuke Arai ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Treatment Duration ◽  
Low Dose ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Maximum Diameter ◽  
Mutation Status ◽  
Formalin Fixed Paraffin Embedded ◽  
Low Dose Chemotherapy ◽  
Ctnnb1 Mutation

11050 Background: Efficacy of low-dose chemotherapy with methotrexate (MTX) and vinblastine (VBL) for desmoid-type fibromatosis (DF) has been reported and approved by many physicians. However, significant factors including biomarker could not be identified to better predict the efficacy of this chemotherapy. Since 2003, meloxicam, which is a selective COX-2 inhibitor, has been applied consecutively as a first line treatment. We applied the low-dose chemotherapy with MTX+VBL for refractory patients. The aim of this study was to reveal the clinical outcome of low-dose chemotherapy with MTX+VBL, and determine the useful factors to predict the efficacy including CTNNB1 mutation status. Methods: Since 2003, 167 cases were histologically diagnosed as DF. Among them, 36 cases were treated with MTX (30mg/M2) +VBL (6mg/M2) chemotherapy. Treatment interval was basically 2 weeks according to our previous study. Effectiveness was evaluated with MRI and/or CT every 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST). Frozen or FFPE (Formalin-Fixed Paraffin-Embedded) specimens obtained at biopsy or previous surgery were subjected to the analyses for CTNNB1 mutation status by Sanger method. Clinical outcome and factors correlating with the efficacy were analyzed. Results: Among 36 cases with this chemotherapy, male was 13, mean age at the treatment was 36±18 years. Mean maximum diameter of tumor was 15±18 cm. Twenty-nine cases (81%) harbored CTNNB1 or APC mutation. Mean treatment duration and cycles of MTX+VBL were 20 months and 29 cycles, respectively. According to RECIST, PD in 2, PR 1n 15, and SD in 19. According to CTCAE, Grade 3 or more adverse events were observed in only one case. CTNNB1 mutation status, gender, age, size, and location did not affect the outcome of RECIST. Longer treatment duration and cycles of chemotherapy were significantly associated with the outcome (P = 0.002 and 0.004, respectively). In 15 cases of PR, recurrent tumors significantly took longer time to get efficacy (P = 0.027), and tumors arising in trunk and extremities tended to take longer time (P = 0.1). Conclusions: Low-dose MTX+VBL chemotherapy is effective and feasible treatment for refractory DF regardless of CTNNB1 mutation status. Occasionally it takes time to obtain objective response.

Low-dose chemotherapy with methotrexate and vinblastine for patients with desmoid tumors: relationship to CTNNB1 mutation status

2015 ◽  
Vol 20 (6) ◽  
pp. 1211-1217 ◽  
Author(s):  
Yoshihiro Nishida ◽  
Satoshi Tsukushi ◽  
Hiroshi Urakawa ◽  
Shunsuke Hamada ◽  
Eiji Kozawa ◽  
...  
Keyword(s):  
Low Dose ◽  
Desmoid Tumors ◽  
Mutation Status ◽  
Low Dose Chemotherapy ◽  
Ctnnb1 Mutation

scholarly journals Efficacy of low-dose chemotherapy with methotrexate and vinblastine for patients with extra-abdominal desmoid-type fibromatosis: a systematic review

2019 ◽  
Vol 50 (4) ◽  
pp. 419-424 ◽  
Author(s):  
Koki Shimizu ◽  
Shunsuke Hamada ◽  
Tomohisa Sakai ◽  
Hiroshi Koike ◽  
Masahiro Yoshida ◽  
...  
Keyword(s):  
Systematic Review ◽  
Low Dose ◽  
Evaluation Criteria ◽  
Case Series ◽  
Evaluation Methodology ◽  
Adverse Event Rate ◽  
Prospective Case Series ◽  
Extra Abdominal Desmoid ◽  
Low Dose Chemotherapy

Abstract Objective The treatment modality for desmoid-type fibromatosis has shifted from surgery to conservative treatment. This systematic review aims to evaluate the efficacy of low-dose chemotherapy with methotrexate and vinblastine for patients with extra-abdominal desmoid-type fibromatosis. Methods We searched the pertinent literature from January 1990 to August 2017. Two reviewers evaluated and screened the literature independently for eligibility and extracted data. We evaluated the quality of body of evidence and made a recommendation according to the Grading of Recommendations Development and Evaluation methodology. Results The search yielded 40 studies, 9 of which were included after the first and second screenings. There were three prospective case series but no randomized controlled trials among the nine studies. There was no case–control report (vs. no treatment). According to Response Evaluation Criteria in Solid Tumors criteria, the mean response rate (complete remission or partial response) was 36% (11–57%). Including stable disease, namely, clinical benefit was consistently as high as 85% (69–100%). Mean adverse event rate of G3 or G4 according to CTCAE was 31%. One study reported improvement of pain (87.5%) because of this chemotherapy. Conclusion The efficacy of this chemotherapy was convincing. However, the overall evidence was weak, and this chemotherapy is not covered by insurance in Japan; we only weakly recommend low-dose chemotherapy with methotrexate and vinblastine in patients with extra-abdominal desmoid-type fibromatosis.

scholarly journals Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 232
Author(s):  
Rashmi G. Shah ◽  
Marine A. Merlin ◽  
Samuel Adant ◽  
Fayçal Zine-Eddine ◽  
Jean-Mathieu Beauregard ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Normal Cells ◽  
Radiation Delivery ◽  
Different Types ◽  
Pre Treatment ◽  
High Doses ◽  
Low Dose Chemotherapy

The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3–7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.

scholarly journals Immunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Changes

2021 ◽  
Vol 20 ◽  
pp. 153473542110026
Author(s):  
Andrana K. Calgarotto ◽  
Ana L. Longhini ◽  
Fernando V. Pericole de Souza ◽  
Adriana S. Santos Duarte ◽  
Karla P. Ferro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Green Tea ◽  
Regulatory T Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Related Factor ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Green tea (GT) treatment was evaluated for its effect on the immune and antineoplastic response of elderly acute myeloid leukemia patients with myelodysplasia-related changes (AML-MRC) who are ineligible for aggressive chemotherapy and bone marrow transplants. The eligible patients enrolled in the study (n = 10) received oral doses of GT extract (1000 mg/day) alone or combined with low-dose cytarabine chemotherapy for at least 6 months and/or until progression. Bone marrow (BM) and peripheral blood (PB) were evaluated monthly. Median survival was increased as compared to the control cohort, though not statistically different. Interestingly, improvements in the immunological profile of patients were found. After 30 days, an activated and cytotoxic phenotype was detected: GT increased total and naïve/effector CD8+ T cells, perforin+/granzyme B+ natural killer cells, monocytes, and classical monocytes with increased reactive oxygen species (ROS) production. A reduction in the immunosuppressive profile was also observed: GT reduced TGF-β and IL-4 expression, and decreased regulatory T cell and CXCR4+ regulatory T cell frequencies. ROS levels and CXCR4 expression were reduced in bone marrow CD34+ cells, as well as nuclear factor erythroid 2–related factor 2 (NRF2) and hypoxia-inducible factor 1α (HIF-1α) expression in biopsies. Immune modulation induced by GT appears to occur, regardless of tumor burden, as soon as 30 days after intake and is maintained for up to 180 days, even in the presence of low-dose chemotherapy. This pilot study highlights that GT extracts are safe and could improve the immune system of elderly AML-MRC patients.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

scholarly journals A Phase 2 Clinical Trial of Trametinib and Low-Dose Dabrafenib in Patients with Advanced Pretreated NRASQ61R/K/L Mutant Melanoma (TraMel-WT)

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2010
Author(s):  
Gil Awada ◽  
Julia Katharina Schwarze ◽  
Jens Tijtgat ◽  
Giuseppe Fasolino ◽  
Hendrik Everaert ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Low Dose ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Skin Toxicity ◽  
Mek Inhibitor ◽  
Phase 2 ◽  
Cutaneous Toxicity ◽  
Full Dose ◽  
Phase 2 Clinical Trial

Background: MEK-inhibitor monotherapy has activity in advanced NRASQ61R/K/L mutant melanoma but is associated with dose-limiting cutaneous toxicity. The combination of a BRAF- with a MEK-inhibitor at their full dose (as in BRAFV600E/K mutant melanoma) has low cutaneous toxicity. It is unknown whether a low dose of BRAF-inhibitor can mitigate the skin toxicity associated with full-dose MEK-inhibitor treatment in patients with advanced NRASQ61R/K/L mutant melanoma. Methods: This two-stage phase 2 clinical trial investigated trametinib 2 mg once daily in patients with advanced NRASQ61R/K/L mutant melanoma who were pretreated with immune checkpoint inhibitors. In case of trametinib-related cutaneous toxicity, low-dose dabrafenib (50 mg twice daily) was added to prevent recurrent cutaneous toxicity (pre-amendment). Following an amendment, trametinib was combined upfront with low-dose dabrafenib (post-amendment). Objective response rate (ORR) served as the primary endpoint. Results: All 6 patients enrolled pre-amendment developed trametinib-related cutaneous toxicity, necessitating treatment interruption. Combining trametinib with low-dose dabrafenib prevented recurrent skin toxicity thereafter. Trametinib-related skin toxicity was effectively mitigated in all 10 patients post-amendment. In all 16 included patients, the ORR and disease control rate was 6.3% (1 partial response) and 50.0%, respectively. The trial was halted after the first stage. Conclusions: Combining full-dose trametinib with low-dose dabrafenib can mitigate MEK-inhibitor-related skin toxicity but was insufficiently active in this patient population. This combination can be of further interest for the treatment of MEK-inhibitor-sensitive tumors.

Abstract P338: Incidence, Predictors and Impact of Infarct in New Territory in Escape Na1 Trial

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Nishita Singh ◽  
Martha Marko ◽  
Petra Cimflova ◽  
Johanna Ospel ◽  
Nima Kashani ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Endovascular Therapy ◽  
Randomized Study ◽  
Maximum Diameter ◽  
Vascular Territory ◽  
Poor Clinical Outcome ◽  
Guide Catheter ◽  
Ct And Mri

Introduction: Infarct in new territory (INT) is a known complication of endovascular therapy. We assessed the prevalence, predictors and clinical relevance of INT Methods: We included patients from the ESCAPE-NA1: a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in patients with acute ischemic stroke who underwent EVT within 12 hours from onset. All imaging was re-evaluated, and INT was defined by presence of infarct in new vascular territory, outside the baseline target occlusion(s) on follow up CT and MRI. INT’s were classified by maximum diameter (<2mm, 2-20mm and >20mm) and location. Results: Of 1099 analyzed patients in ESCAPE NA1, 107 had INT (9.7%, mean age 67 years, 51.4% females). There were no differences at baseline in those with vs without INT. Most INTs (75.7%) were angiographically occult and 41(38.3%) were > 20mm. The most common INT territory was the ACA alone or in combination with MCA/PCA (30.3%). The presence of emboli in new territory angiographically was significantly associated with INT (OR 16.39, 95%CI 8.14-33.09). Alteplase use, balloon guide catheter use, nerinetide and initial occlusion site did not predict INT. INT patients had higher final median infarct volumes compared to non-INT (44.5cc vs 23.3cc, P<0.001). Large INT (diameter of >20mm) were associated with poor clinical outcome compared to INT (<2mm) OR (mRS 0-2) 0.17, 95%CI 0.05-0.55). Conclusion: Infarcts in new territory are common and are associated with poor outcome.

Sorafenib in Combination With Gemcitabine in Recurrent Epithelial Ovarian Cancer: A Study of the Princess Margaret Hospital Phase II Consortium

2010 ◽  
Vol 20 (5) ◽  
pp. 787-793 ◽  
Author(s):  
Stephen A. Welch ◽  
Hal W. Hirte ◽  
Laurie Elit ◽  
Russel J. Schilder ◽  
Lisa Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Stable Disease ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Ca 125 ◽  
Response Evaluation ◽  
Time To Progression ◽  
Response Evaluation Criteria

Objectives:Antiangiogenic strategies have demonstrated efficacy in epithelial ovarian cancer (EOC). Sorafenib is a novel multitargeted kinase inhibitor with antiangiogenic activity. Gemcitabine has known activity against EOC. A phase 1 clinical trial of this combination suggested activity in ovarian cancer with no dose-limiting toxicity. This phase 2 study was designed to examine the safety and efficacy of gemcitabine and sorafenib in patients with recurrent EOC.Methods:Patients with recurrent EOC after platinum-based chemotherapy and who had subsequently received up to 3 prior chemotherapy regimens were eligible. Gemcitabine (1000 mg/m2 intravenous [IV]) was administered weekly for 7 of 8 weeks in the first cycle, then weekly for 3 weeks of each subsequent 4-week cycle. Sorafenib (400 mg p.o. bid) was given continuously. The primary end point for this trial was objective response rate by the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included Gynecologic Cancer Intergroup (GCIG) CA-125 response, time to progression, overall survival, and toxicity.Results:Forty-three patients were enrolled, and 33 completed at least 1 cycle. Two patients had a partial response (Response Evaluation Criteria in Solid Tumors objective response rate = 4.7%). Ten patients (23.3%) maintained response or stable disease for at least 6 months. GCIG CA-125 response was 27.9%. The median time to progression was 5.4 months, and the median overall survival was 13.0 months. Hematologic toxicity was common but manageable. The most common nonhematologic adverse events were hand-foot syndrome, fatigue, hypokalemia, and diarrhea.Conclusion:This trial of gemcitabine and sorafenib in recurrent EOC did not meet its primary efficacy end point, but the combination was associated with encouraging rates of prolonged stable disease and CA-125 response.

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