A Phase II Study of Low Dose Intravenous Clofarabine for Elderly Myelodysplastic Syndrome Patients Who Have Failed 5-Azacytidine

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4955-4955
Author(s):  
Seah H Lim ◽  
John McMahan ◽  
Jian Zhang ◽  
Yana Zhang
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Disease Progression ◽  
Phase Ii ◽  
Low Dose ◽  
Response Rate ◽  
Phase Ii Study ◽  
Low Risk ◽  
The Other ◽  
Low Doses

Abstract Abstract 4955 Based on the observations of changes in DNA methylation status of various tumor suppressor genes, epigenetic targeting of myelodysplastic syndrome (MDS) with DNA hypomethylating agents are currently used for these patients. However, only up to 40% of the patients respond to these treatments. Therapeutic options for non-responders or responders whose disease progresses while on therapy are very limited. Based on our recent findings that low concentration clofarabine induced DNA hypomethylation, we carried out a Phase II study of elderly MDS patients who had failed 5-azacytidine (5-aza) therapy to determine the efficacy and toxicities of low dose intravenous clofarabine (ClinicalTrials.gov Identifier NCT00700011). Patients in Cohort 1 received intravenous clofarabine at 10 mg/m2/day and patients in Cohort 2 5 mg/m2/day for 5 days, each infusion given over 2 hours and each cycle repeated every 4 to 8 weeks, depending on the rate of bone marrow recovery. Eight patients were planned for each of the treatment dose. The patients were treated until disease progression or intolerable toxicities. The International Working Group response criteria were used. The study was closed after 10 patients were treated. Of the 10 patients (6 males and 4 females) treated, ei8 received 10 mg/m2/day (Cohort 1) of clofarabine and 2 patients 5 mg/m2/day (Cohort 2). The median age was 73 years (range 65–78). Five patients had only received 5-aza prior to being treated with clofarabine while the other 5 patients had also received other therapy (lenolidomide and decitabine). Three patients received 1 cycle, 4 patients received 2 cycles, 1 patient received 3 cycles and 2 patients received 4 cycles of clofarabine. The following responses were observed in the 9 evaluable patients: 1 CR (11%), 1 PR (11%), 2 HI (22%), 3 SD and 2 PD. The overall response rate was 44% in this group of elderly patients. All responses were observed in patients who received clofarabine 10 mg/m2/day. Response rate of 67% (4/6) was observed in patients with low risk MDS (IPSS < 1). In contrast, all 3 evaluable patients with high risk/Int.-2 MDS showed disease progression. The median time to response was 6 weeks (range 4–6 weeks) and 1 cycle of clofarabine. The patient who achieved a CR remained in CR for 14 months. The 2 patients who achieved HI both restored the erythroid-responsiveness to recombinant erythropoietin and became transfusion-independent, both for 10 months (1 patient received only 1 cycle and the other patient 2 cycles of clofarabine). As of July 31, 2010, diseases in all four responders have relapsed/progressed. The median duration of response was 10 months (range 5–14). Despite using low doses of clofarabine, severe and prolonged pancytopenia was observed in all 10 patients. All 10 patients needed considerable blood and platelet transfusions. Eight of these ten patients also needed hospitalization for neutropenic fever. Of the 22 cycles of clofarabine administered, there were a total of 13 hospital admissions with 100 hospital days. A total of 169 units of irradiated packed red blood cells (median 10 units/cycle; range 1.5–14 units/cycle) and 211 units of irradiated single donor platelets (median 10 units/cycle; range 2–30.5 units/cycle) were used. One patient died, within 2 weeks of completing cycle 1 of clofarabine, from intracranial bleed despite intensive support of severe thrombocytopenia with aggressive platelet transfusion. This patient was already thrombocytopenic prior to starting clofarabine and had a history of severe thrombocytopenic gastrointestinal bleed prior to starting on clofarabine. Nonhematologic toxicities occurred very infrequently and were mainly Grade 2 or lower. In all cases, clofarabine was discontinued due to either disease progression (2 patients) or toxicities (8 patients). With a median follow-up of 7.5 months (range 0.5–22), the overall survival for the whole group was 50%. In conclusion, elderly MDS patients, especially those with low risk disease, who have failed 5-aza may respond to low dose clofarabine. However, even at the low doses used in this study, bone marrow toxicity was significant. It remains to be determined whether the dose of clofarabine can be reduced further to minimize toxicities without compromising efficacy in this group of patients. Future studies should investigate the role of low dose clofarabine in low risk MDS patients. Study supported by Genzyme Corporation, Cambridge, MA, USA Disclosures: No relevant conflicts of interest to declare.

Flow Cytometric Detection of Human Telomerase Reverse Transcriptase Expression in CD34 Positive Precursor Fraction in Myelodysplastic Syndrome Bone Marrow.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4300-4300
Author(s):  
Hiroshi Handa ◽  
Takafumi Matsushima ◽  
Norifumi Tsukamoto ◽  
Masamitsu Karasawa ◽  
Hiroyuki Irisawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Disease Progression ◽  
Risk Group ◽  
Telomerase Activity ◽  
Low Risk ◽  
Htert Expression ◽  
Trap Assay

Abstract Telomerase activity has been found in most common cancers indicating that telomerase detection may be a useful marker in cancer diagnosis. For detection of telomerase activity and the expression of associated genes in cells, TRAP assay and RT-PCR are customarily used. Immunohistochemical detection of hTERT is useful to detect telomerase-positive cells in a background of non- cancerous cells. We developed a method for the detection of intra-nuclear hTERT protein, in a sub-population of hematopoietic cells, using concurrent staining cell surface antigen and multi color flow cytometry. Human leukemia and myeloma cell lines showed 100% positivity, whereas neutrophils of normal subjects showed 0% positivity, it is consistent with telomerase activity assessed by TRAP assay (r=0.71, p&lt;0.0001) and previous observations. Then we applied this method to analyze hTERT expression in myelodysplastic syndrome (MDS). Forty MDS patients samples were obtained, 36 patients were diagnosed as low risk MDS (RA), 14 patients were diagnosed as high risk MDS (RAEB or RAEB-t) according to FAB classification. All samples were acquired after informed consent was obtained from the patients. Expression of hTERT protein was higher in CD34-positive blast-gated cells than CD34-negative blast-gated cells. The percentage of the CD34+ cells expressing hTERT ranged from 9.66% to 90.91% in low risk MDS patients, whereas from 50.46% to 97.68% in high risk MDS. The expression level was higher in the high risk group compared to that in the low risk group in MDS (p=0.0054, p=0.0084). This observation implied that telomerase up-regulation and hTERT expression were important for disease progression and could be a marker of more advanced disease. In subsets of MDS and AML bone marrow specimens obtained from these patients, we examined the hTERT expression in CD34+/CD38 high cells and CD34+/CD38 low cells containing stem cell fraction. Of interest, some of the patients showed higher expression of hTERT in CD34+/CD38 low cells than in CD34+/CD38 high cells. This observation is inconsistent with previous reports describing normal bone marrow hematopoietic cell findings. We speculated that this phenomenon could be a marker of MDS abnormality and that telomerase up-regulation may be initiated in the more primitive precursor fraction containing hematopoietic stem cells during the disease progression. Telomerase studies may be useful for definition of the risks associated with disease severity. Multi-parameter nature of flow cytometry and its ability to identify cellular sub-populations will facilitate a fuller understanding of the mechanisms of activation of telomerase.

A phase II study of sEphB4-HSA in metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS274-TPS274
Author(s):  
Michael C. Burns ◽  
Vinay Sagar ◽  
Borko Jovanovic ◽  
Alicia K. Morgans ◽  
David James VanderWeele ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Cancer Tissue ◽  
Tumor Cell Death ◽  
Overall Response ◽  
Castration Resistant ◽  
Psa Response

TPS274 Background: The EphB4/EphrinB2 pathway is a promising therapeutic target for patients with mCRPC. EphB4 expression is increased in prostate cancer tissue and cell lines, and retained in castration resistant states. EphB4 crosstalks with the PI3K/AKT and MAPK pathways to regulate cell survival and proliferation, and its interaction with the transmembrane ligand EphrinB2 leads to T-cell suppression and immune evasion. A soluble decoy EphB4 receptor-human serum albumin fusion protein (sEphB4-HSA) binds to EphrinB2 and blocks interaction with the cell surface EphB4 receptor to promote immune infiltration and induce tumor cell death. Here we report an ongoing phase II study exploring the preliminary efficacy and safety of sEphB4-HSA in patients with progressive disease after frontline therapy for mCRPC. Methods: Eligibility criteria include mCRPC with disease progression after second generation AR targeted therapy (i.e., abiraterone or enzalutamide), ECOG PS ≤ 2, and adequate renal, hepatic and hematological functions. Pts having received 4 or more prior treatment therapies for mCRPC are excluded. The primary objective is efficacy as reflected by PSA response using PCWG3 criteria. Secondary objectives include safety and tolerability by CTCAE v 5.0, time to PSA progression, overall response by RECIST 1.1 and PCWG3 (bone) criteria, and rPFS. Translational endpoints include expression of EphB4 and EphrinB2 in metastatic tumor samples by immunohistochemistry and correlation with alterations in MYC, PTEN/PI3K, AR, and p53 pathways. sEphB4-HSA is administered as IV infusion over 60 min every 14 days with spacing to every 21 days after 6 cycles. Therapy will continue till disease progression, unacceptable toxicity, treatment delay ≥4 weeks, or patient withdrawal. Preliminary efficacy will be assessed using PSA response rate (PR and CR) with a Simon two stage minimax trial design assuming the undesirable overall response rate (null hypothesis) to be approximately 10% or less, and the alternate hypothesis suggesting success to be approximately 30% or more. Toxicity will be evaluated by the DSMC after the first stage including 15 patients. If 2 or more respond, then an additional 10 patients will be added. Clinical trial information: NCT04033432.

Cetuximab plus docetaxel-cisplatin (DC) as first-line treatment for locally advanced or metastatic gastric cancer: Preliminary results of a phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15592-e15592
Author(s):  
J. Fahlke ◽  
K. Ridwelski ◽  
A. Florschuetz ◽  
E. Kettner ◽  
M. Leithaeuser ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Published Data ◽  
First Line ◽  
Overall Response ◽  
Grade 3

e15592 Background: Based on promising published data, this multicenter, phase II study was initiated to investigate a combined treatment using DC and cetuximab in the first-line setting for patients with gastric cancer. Methods: Patients aged 18–75 years with stage III (T4, nonresectable) or stage IV gastric cancer, ECOG performance status (PS) ≤2, and life expectancy ≥3 months were recruited to receive cetuximab (400 mg/m2 on day 1 then 250 mg/m2 q1w) and DC (D 75 mg/m2 and C 75 mg/m2; both as 1-h infusions on day 1 and then q3w). Treatment was stopped in the event of disease progression, intolerable toxicity, or consent withdrawal. Tumor staging was performed after cycle 3 and then every 12 weeks. The primary endpoint was overall response rate and secondary endpoints included time to progression, overall survival and toxicity. Planned accrual was 79 patients. A per-protocol interim response analysis was planned for the initial 20 evaluable patients. Results: Preliminary data are available for 30 patients; median age 64 [range: 40–73] years; median ECOG PS 1 [range: 0–2]; adenocarcinoma 87%. Median cycles administered were 3 [range: 1–14] and the median follow-up was 1.63 months. The overall response rate was 27.3% (complete response, n=1; partial response, n=5). Stable disease was observed in 10 patients, and disease progression in 6 patients. The most relevant NCI-CTC grade 3–4 hematologic events per patient were leukopenia and neutropenia (73%), anemia (13%), and febrile neutropenia (10%). Major grade 3–4 nonhematologic toxicities were nausea (30%), vomiting (20%), diarrhea (13%), acne (13%), and fatigue (13%). Conclusions: DC and cetuximab were well tolerated and resulted in promising response rates and a predictable toxicity profile. The study is ongoing. No significant financial relationships to disclose.

Low-dose versus standard-dose gemcitabine infusion and cisplatin for patients with advanced bladder cancer: A randomized phase II trial.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 266-266 ◽  
Author(s):  
H. Khaled ◽  
F. Abu-Taleb ◽  
R. Haggag ◽  
A. Zekri
Keyword(s):  
Bladder Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Low Dose ◽  
Response Rate ◽  
Phase Ii Trial ◽  
High Dose ◽  
Prolonged Infusion ◽  
Significant Difference ◽  
Gemcitabine And Cisplatin

266 Background: Bladder carcinoma is the foremost oncologic problem in Egypt. Prolonged infusion of gemcitabine and cisplatin is an effective treatment for advanced bilharzial-related bladder cancer based on a previously published phase II trial. Methods: To compare efficacy and safety of both prolonged infusion and standard gemcitabine-cisplatin combination, this phase II randomized study of 60 untreated patients with stage III/IV bladder cancer was conducted. Patients were randomized to receive either gemcitabine (250 mg/m2) 6-hour infusion on days 1 and 8, and cisplatin (70 mg/m2) on day 2 every 21-day cycle (Arm1) or gemcitabine (1,250 mg/m2) 30-min infusion on days 1 and 8, and cisplatin (70 mg/m2) on day 2 every 21-day cycle (Arm 2). Results: The 47 males and 13 females had a median age of 60 years (range 40-73 years). A total of 44 patients had transitional cell, 12 had squamous cell, and 4 had undifferentiated cell carcinoma. Among the 53 evaluable patients (26 patients in arm1 and 27 patients in arm 2), complete response rate was achieved in 19.3% (5/26 patients of arm 1) and 7.4% (2/27 patients of arm 2). Eight patients in arm 1 (30.7%) and 7 patients (25.9%) in arm 2 had partial response on therapy. Thus the overall response rate of patients in arm1 and arm 2 was 50% (13/26 patients) and 33.3% (9/27patients), respectively (p = 0.21). No significant difference in median time to disease progression (6.7 months versus 7.9 months, p = 0.42), median survival (9.7 months versus 8.8 months, p = 0.3), and 1-year survival (27% versus 6%, p = 0.3) was detected between arms 1 and 2, respectively. No treatment- related deaths occurred. Main hematologic and nonhematologic toxicities were similar in both arms with no statistically significant differences. Conclusions: In the treatment of advanced bilharzial bladder cancer, gemcitabine in low dose and prolonged infusion in combination with cisplatin is not inferior to high-dose short infusion gemcitabine and cisplatin in terms of overall survival, time to disease progression, and response rates with favorable toxicity profile and less financial costs. No significant financial relationships to disclose.

Phase II study of biweekly dose-intense docetaxel plus gemcitabine (GEM/DOC) in patients with recurrent locoregional or metastatic head and neck squamous cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5534-5534 ◽  
Author(s):  
Ammar Sukari ◽  
Zyad Kafri ◽  
Lance K. Heilbrun ◽  
George H. Yoo ◽  
Heather a Mulrenan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Disease Progression ◽  
Annual Meeting ◽  
Phase Ii ◽  
Squamous Cell ◽  
Response Rate ◽  
Phase Ii Study ◽  
Neck Squamous Cell Carcinoma

5534 Notice of Retraction: "Phase II study of biweekly dose-intense docetaxel plus gemcitabine (GEM/DOC) in patients with recurrent locoregional or metastatic head and neck squamous cell carcinoma." ASCO's Confidentiality Policy requires that abstracts be considered confidential and embargoed from the time of submission until the findings have been publicly released in conjunction with the ASCO Annual Meeting. Abstract 5534, published in the 2012 Annual Meeting Proceedings Part I, a supplement to the Journal of Clinical Oncology, violated this policy and has been retracted from publication and presentation at the 2012 ASCO Annual Meeting. Background: Patients with metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, limited treatment options, and median survival of 6 to 9 months. Docetaxel and gemcitabine have both shown activity in HNSCC. The optimal combination, dosing, and scheduling of both drugs is, however, unknown. Thus, we investigated the efficacy and safety of biweekly dose intense GEM/DOC in patients with recurrent locoregional or metastatic HNSCC. Methods: An open-label, single-institution, single-arm, phase II study was conducted for patients who were previously treated with no more than two cytotoxic regimens. The patients received docetaxel (60 mg/m2IV) and gemcitabine (3000 mg/m2 IV) on day 1. The treatments were repeated every 14 days (one cycle), until disease progression or unacceptable toxicity. The primary end point was response rate. RECIST-defined response was evaluated every 4 cycles and toxicities were evaluated at each cycle. Results: A total of 36 patients were enrolled (M:F 26:10; median age (range), 60 years (46-79); performance status 0-1) , 29 of whom were response-evaluable. The patients received a median of 4 cycles (range 0-24). Of these 29 patients, none achieved complete response (CR) and 6 demonstrated a partial response (PR). Thus, the overall response rate was 21% (95% confidence interval [CI], 0.10 – 0.38). Ten patients had stable disease (SD), resulting in tumor control (CR or PR or SD) in 16 of 29 patients (55%), whereas 13 patients (45%) had disease progression. The median response duration was 3.2 months (80% CI: 2.0 – 6.1 months). For all 36 patients, the median overall survival was 4.2 months (95% CI: 2.4 – 7.0 months). Myelosuppression was the most common adverse event. Grade 3-4 neutropenia and anemia were observed in 10 (30%) and 13 (39%) patients, respectively. None of these patients, however, had febrile neutropenia or bleeding events, and there were no treatment-related deaths. Conclusions: The combination of biweekly dose intense GEM/DOC was tolerable and active regimen in patients with recurrent locoregional or metastatic HNSCC. Our findings warrant further investigation in a larger patient population.

A Phase II Study of Nilotinib, a Novel Inhibitor of c-Kit, PDGFR, and Bcr-Abl, Administered to Patients with Systemic Mastocytosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2703-2703 ◽  
Author(s):  
Andreas Hochhaus ◽  
Oliver G. Ottmann ◽  
STephanie Lauber ◽  
Timothy Hughes ◽  
Gregor Verhoef ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Adverse Events ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Systemic Mastocytosis ◽  
Clinical Indication ◽  
Kit Mutation ◽  
Cell Counts

Abstract Systemic mastocytosis is a clonal disorder associated with a constitutive activation of the c-kit tyrosine kinase based on point mutations and is characterized by mast cell infiltration of extracutaneous organs. Nilotinib is a novel aminopyrimidine which potently inhibits Bcr-Abl, as well as the PDGF-R, and c-kit tyrosine kinases. Preclinical data demonstrated the activity of nilotinib against D816V mutated c-kit in biochemical and cellular assays. This Phase II study was designed to evaluate the safety and efficacy of nilotinib administered at an oral dose of 400 mg twice daily to patients with systemic mastocytosis defined by specific disease criteria and with a clinical indication for treatment. Data are available for 60 patients (34 male, 26 female). The median age is 51 years (range, 29 to 79). Of the 60 patients 31 (52%) had extramedullary involvement at baseline. In 30/36 patients investigated (83%) D816V c-kit mutation was found by D-HPLC and/or conventional sequencing in bone marrow or extracutaneous organs. Two patients showed the c-kit I798I polymorphism. Treatment is ongoing for 38 (63%) patients; 22 (37%) have discontinued; ten (17%) for adverse events, seven (12%) withdrew consent, and one (2%) each for disease progression and lost to follow-up. There were two (3%) deaths related to disease progression. Based on investigators’ assessment of serum tryptase, bone marrow mast cell counts and improvement of clinical symptoms 12 patients (20%) had a documented clinical response including two (3%) complete, five (8%) incomplete, four (7%) minor, and one partial response. Adverse events occurring in >15% of patients included nausea in 28 (47%), headache in 26 (43%), fatigue in 25 (42%), vomiting in 22 (37%), diarrhea in 21 (35%), pruritis in 16 (27%), and rash in 15 (25%) patients, dizziness and muscle spasms in 14 (23%) patients each, bone pain in 12 (20%), pyrexia and myalgias in 11 (18%) patients each, and dyspnea, constipation, increased ALAT, and arthralgias in ten (17%) patients each. Most side effects occurred early after initiation of nilotinib therapy and were successfully treated with H1- and H2-blockers and/or corticosteroids, indicating a mast cell degranulation syndrome. Overall the most frequent Grade 3/4 adverse events included diarrhea in four (7%) patients, and thrombocytopenia and headache in three (5%) patients each. The data suggest that nilotinib has clinical activity and an acceptable safety and tolerability profile in patients with systemic mastocytosis with constitutive c-kit activation. Individual molecular characterization will help to guide targeted therapy in this disease.

Low-Dose 5-Aza-2′-Deoxycytidine, a DNA Hypomethylating Agent, for the Treatment of High-Risk Myelodysplastic Syndrome: A Multicenter Phase II Study in Elderly Patients

2000 ◽  
Vol 18 (5) ◽  
pp. 956-956 ◽  
Author(s):  
P. Wijermans ◽  
M. Lübbert ◽  
G. Verhoef ◽  
A. Bosly ◽  
C. Ravoet ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Myelodysplastic Syndrome ◽  
Survival Time ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Response Duration ◽  
Multicenter Phase ◽  
Dna Hypomethylating Agent

PURPOSE: 5-Aza-2′-deoxycytidine (decitabine; DAC) is a DNA hypomethylating agent that has shown a 50% response rate in a small phase II study in elderly patients with high-risk myelodysplastic syndrome. We performed a second, multicenter phase II study in a larger group of patients to confirm our findings and to study the toxicity of DAC. PATIENTS AND METHODS: Between June 1996 and September 1997, 66 patients (median age, 68 years) from seven centers received DAC 45 mg/m2/d for 3 days every 6 weeks. For patients in whom a complete response (CR) was reached after two courses, two further cycles were administered as consolidation therapy. In case of a stable disease situation, improvement, or a partial response (PR), a maximum of six cycles was administered. The primary end points were response rate and toxicity. The secondary end points were response duration, survival from the start of therapy, and overall survival. RESULTS: The observed overall response rate was 49%, with a 64% response rate in the patients with an International Prognostic Scoring System (IPSS) high-risk score. The actuarial median response duration was 31 weeks, with a response duration of 39 weeks and 36 weeks for patients who reached a PR or CR, respectively. The actuarial median survival time from the time of diagnosis was 22 months and from the start of therapy was 15 months. For the IPSS high-risk group, the median survival time was 14 months. The median progression-free survival time was 25 weeks. Myelosuppression was rather common, and the treatment-related mortality rate was 7% and was primarily associated with pancytopenia and infection. Significant responses were observed with regard to megakaryopoiesis, with increases in platelet counts having already occurred after one cycle of DAC therapy in the majority of the responding patients. CONCLUSION: We were able to confirm our previous observation that DAC therapy was effective in half of the studied patients with high-risk myelodysplastic syndrome and is especially active in the patients with the worst prognoses. Myelosuppression was the only major adverse effect observed.

Phase II Study on the Effect of Disease Sites, Age, and Prior Therapy on Response to Iodine-131-Metaiodobenzylguanidine Therapy in Refractory Neuroblastoma

2007 ◽  
Vol 25 (9) ◽  
pp. 1054-1060 ◽  
Author(s):  
Katherine K. Matthay ◽  
Gregory Yanik ◽  
Julia Messina ◽  
Alekist Quach ◽  
John Huberty ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Soft Tissue ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Hematopoietic Stem ◽  
Prior Therapy ◽  
Treatment Regimens ◽  
Iodine 131

Purpose To evaluate the effect of disease sites and prior therapy on response and toxicity after iodine-131-metaiodobenzylguanidine (131I-MIBG) treatment of patients with resistant neuroblastoma. Patients and Methods One hundred sixty-four patients with progressive, refractory or relapsed high-risk neuroblastoma, age 2 to 30 years, were treated in a limited institution phase II study. Patients with cryopreserved hematopoietic stem cells (n = 148) were treated with 18 mCi/kg of 131I-MIBG. Those without hematopoietic stem cells (n = 16) received 12 mCi/kg. Patients were stratified according to prior myeloablative therapy and whether they had measurable soft tissue involvement or only bone and/or bone marrow disease. Results Hematologic toxicity was common, with 33% of patients receiving autologous hematopoietic stem cell support. Nonhematologic grade 3 or 4 toxicity was rare, with 5% of patients experiencing hepatic, 3.6% pulmonary, 10.9% infectious toxicity, and 9.7% with febrile neutropenia. The overall complete plus partial response rate was 36%. The response rate was significantly higher for patients with disease limited either to bone and bone marrow, or to soft tissue (compared with patients with both) for patients with fewer than three prior treatment regimens and for patients older than 12 years. The event-free survival (EFS) and overall survival (OS) times were significantly longer for patients achieving response, for those older than 12 years and with fewer than three prior treatment regimens. The OS was 49% at 1 year and 29% at 2 years; EFS was 18% at 1 year. Conclusion The high response rate and low nonhematologic toxicity with 131I-MIBG suggest incorporation of this agent into initial multimodal therapy of neuroblastoma.

Phase II study of low-dose interleukin-11 in patients with myelodysplastic syndrome

2006 ◽  
Vol 47 (10) ◽  
pp. 2049-2054 ◽  
Author(s):  
Alberto J. Montero ◽  
Zeev Estrov ◽  
Emil J. Freireich ◽  
Issa F. Khouri ◽  
Charles A. Koller ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Study ◽  
Interleukin 11

Phase II study of combining immunotherapy and pulsed low dose rate radiotherapy for abdominal metastasis of gastric cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16099-e16099
Author(s):  
Yang Yang ◽  
Jing Yan ◽  
Juan Liu ◽  
Shuangshuang Li ◽  
Shanbao Gao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Low Dose ◽  
Response Rate ◽  
Phase Ii Study ◽  
Low Dose Rate ◽  
Line Therapy ◽  
Abdominal Metastasis

e16099 Background: Immune-mediated responses against tumor antigens by checkpoint inhibitors (CPIs) may be enhanced by radiotherapy and the combination may hold therapeutic promise. Pulsed low dose rate radiotherapy (PLDR) is an effective strategy for abdominal tumor by taking advantage of low dose hyper-radiosensitivity with maximizing tumor response and minimizing adverse events by radiotherapy. In this phase II study, we prospectively analyzed the response and adverse events of the combination strategy of CPIs and PLDR for abdominal metastasis of gastric cancer. Methods: Eligibility criteria included pathologically confirmed advanced gastric adenocarcinoma with abdominal metastasis. Patients received XELOX regimen chemotherapy, anti-PD-1 toripalimab, and PLDR for abdominal metastasis, prescription dose was 50-56Gy/25-28f. The primary endpoint was objective response rate (ORR) and safety. Secondary endpoints were regional response rate (RRR) and regional controlled rate (RCR) for radiotherapy target tumor, progression-free survival (PFS), and overall survival (OS). Results: Between November 2018 and June 2020, 24 patients were enrolled and included in the efficacy analysis. 13 of them were first line therapy, and 11 of them were second line therapy. The ORR was 70.8% and the combination regimen were tolerable. The RRR was 83.3% and the RCR was 95.8%. The median PFS was 11.1 months and the median OS was not yet reached. Conclusions: In this phase II clinical trial, the combination of Immunotherapy and radiotherapy provided good response and toleration for abdominal metastasis of gastric cancer. It suggested clinical efficacy of this regimen in patients with advanced gastric cancer. Clinical trial information: NCT03061162.

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