Alternative Schedule of Filgrastim after Autologous Transplantation: Less Dosing, Same Efficacy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4334-4334
Author(s):  
Aida B. Sousa ◽  
Fatima Costa ◽  
Gilda Ferreira
Keyword(s):  
Pilot Study ◽  
Median Time ◽  
Autologous Transplantation ◽  
Standard Of Care ◽  
Control Group ◽  
Study Group ◽  
Current Standard ◽  
Transfusion Requirements ◽  
Clinical Instability ◽  
Grade 3

Abstract Administration of colony-stimulating factors (CSF) after autologous peripheral-blood progenitor cell transplantation is the current standard of care, and G-CSF is usually given from day +5 or +7 until engraftment. Recent preliminary data in a non-transplant setting suggest that 2 doses of G-CSF may be equivalent to the standard schedule. In this pilot study, we evaluated the safety and efficacy of giving only 2 doses of filgrastim post-transplant (days +7 and +9) in non-myeloma pts; exclusion criteria were re-transplants and clinical instability at day +7. From July 07 to June 08, 19 consecutive pts were included (16 lymphomas, 3 acute leukaemias) and their outcome was compared to a historical control group of 42 similar pts transplanted from Jan 06 to Jun 07, who received filgrastim from d+7 until 1000 neutrophils/ul (4–18 days, median 9). There were no significant differences in primary endpoints: median time to neutrophil engraftment (500/ul reached on day +12 vs +11) rate of documented infections (with bacteremia in 23% of transplants in the study group vs 36% in the control group) and median length of hospitalisation (both 22 days). Median duration of intravenous antibiotics (11 vs 12 days) median time to platelet engraftment (20,000/ul reached on day +13 vs +14) incidence of grade 3/4 mucositis and transfusion requirements were also similar. There were no deaths at day +30 in the study group. In 2 of the 19 pts a secondary prescription of filgrastim was made (for 2 and 4 days). In this pilot study, reducing filgrastim administration to 2 doses seems possible without undue risks. If confirmed in a randomized trial, these findings could have a significant impact on the cost of transplantation.

EXTH-56. ZIKA VIRUS TREATMENT SIGNIFICANTLY PROLONGS SURVIVAL IN A GLIOBLASTOMA PATIENT DERIVED XENOGRAFT MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi175-vi176
Author(s):  
Parvez Akhtar ◽  
Samuel Zwernik ◽  
Deborah Donohoe ◽  
Catherine Warner ◽  
Dmitry Bosenko ◽  
...  
Keyword(s):  
Median Survival ◽  
Zika Virus ◽  
Oncolytic Virus ◽  
Xenograft Model ◽  
Standard Of Care ◽  
Control Group ◽  
Current Standard ◽  
Patient Derived Xenograft ◽  
Current Standard Treatment ◽  
Tumor Remission

Abstract The poor median survival for patients with glioblastoma (GBM) of 15 months has not budged for the past 15 years, when the current standard treatment was first approved. There is no standard of care chemotherapy for recurrent GBM. We previously showed that Zika virus (ZIKV) tropism for GBM cells is mediated through the receptor tyrosine kinase, AXL. This infection is cytotoxic. In this study we show that ZIKV is an effective oncolytic virus in a patient derived xenograft model. Fox N1 Nude homozygous female mice 6-8-weeks-old were grouped into 4 experimental arms: two patient derived cell lines, each with a ZIKV treated and a control group. There were 12 mice in each arm. Animals received subcutaneous flank injections of GBM 8049 or its AXL CRISPR knockout 8049 AXLKO (2x106 cells). When tumors reached 200 mm3, mice received intra-tumoral injection of 2.5x106 ZIKV particles or saline. ZIKV induced complete tumor remission in 22 of 24 animals (8049: 11/12; 8049 AXLKO: 11/12). There was no tumor remission in the saline treated animals. Median survival of 8049 and 8049 AXLKO ZIKV treated mice was 124 days and 125 days, respectively. This is compared to median survival of control animals 8049: 42 days; 8049 AXLKO: 46 days (P= 0.001). Among ZIKV treated mice, there were two recurrences: one in the 8049 tumor (24 days after significant tumor remission) and one 8049 AXLKO tumor (7 days after significant tumor remission). We conclude that ZIKV should be considered a candidate oncolytic virus for GBM.

Is Treatment of Segond Fracture Necessary With Combined Anterior Cruciate Ligament Reconstruction?

2017 ◽  
Vol 46 (4) ◽  
pp. 832-838 ◽  
Author(s):  
Heath P. Melugin ◽  
Nick R. Johnson ◽  
Isabella T. Wu ◽  
Bruce A. Levy ◽  
Michael J. Stuart ◽  
...  
Keyword(s):  
Pivot Shift ◽  
Cruciate Ligament ◽  
Control Group ◽  
Study Group ◽  
Activity Levels ◽  
Segond Fracture ◽  
Acl Tear ◽  
Significant Difference ◽  
Ikdc Score ◽  
Grade 3

Background: There is a paucity of clinical information to guide the treatment of a combined anterior cruciate ligament (ACL) tear and Segond fracture. Purpose: To compare clinical outcomes, graft failure rates, and activity levels between patients undergoing ACL reconstruction (ACLR) with and without an untreated Segond fracture at a minimum 2-year follow-up. Study Design: Cohort study; Level of evidence, 3. Methods: This study included a group of patients with a combined ACL tear/untreated Segond fracture that was matched based on age, sex, body mass index, and graft type to a control group of patients with an ACL tear and no Segond fracture. All patients were treated with ACLR alone between the years of 2000 and 2015. The diagnosis of a Segond fracture, or bony avulsion of the anterolateral complex, was made by radiographic analysis. Data regarding the initial injury, surgical intervention, and physical examination findings were recorded. Clinical and functional outcomes were obtained using physical examination results, International Knee Documentation Committee (IKDC) subjective scores, and Tegner activity levels. Results: Twenty patients (16 male, 4 female) with a combined ACL tear/untreated Segond fracture with a mean age of 26.3 years (range, 13-44 years) were matched to a control group of 40 patients (32 male, 8 female) with an ACL tear and no Segond fracture with a mean age of 26.4 years (range, 13-47 years). The study group was followed for a mean of 59.1 months (range, 24-180 months) and the control group for a mean of 55.5 months (range, 24-120 months). The mean IKDC score was 86.5 (range, 54-100) for the study group compared with 93.0 (range, 54-100) for the control group ( P = .03). The graft rupture rate was 10% for both groups ( P = .97). The mean time to rupture was 33.0 months (range, 21-45 months) in the study group and 63.5 months (range, 39-88 months) in the control group ( P = .24). Patients in the study group had significantly more anteroposterior instability by preoperative Lachman testing than those in the control group (control group: 0 normal, 3 grade 1+, 37 grade 2+, 0 grade 3+; study group: 0 normal, 1 grade 1+, 10 grade 2+, 9 grade 3+; P = .0001). There was no significant difference between the 2 groups in regard to postoperative Lachman testing (control group: 35 normal, 3 grade 1+, 2 grade 2+, 0 grade 3+; study group: 17 normal, 3 grade 1+, 0 grade 2+, 0 grade 3+; P = .31). Patients in the study group had significantly more instability by preoperative pivot-shift testing than those in the control group (control group: 0 normal, 7 grade 1+, 33 grade 2+, 0 grade 3+; study group: 1 normal, 1 grade 1+, 11 grade 2+, 7 grade 3+; P = .0003). No significant difference was found between the 2 groups for postoperative pivot-shift testing (control group: 36 normal, 2 grade 1+, 2 grade 2+, 0 grade 3+; study group: 18 normal, 1 grade 1+, 1 grade 2+, 0 grade 3+; P = .61) or final Tegner activity level (median, 6). Conclusion: At midterm follow-up, patients undergoing ACLR with and without a Segond fracture had similar pivot-shift test results, graft failure rates, and activity levels. The IKDC score was statistically worse in the patients with a combined ACL tear/untreated Segond fracture, but the difference was less than the minimal clinically important difference for the IKDC score. These findings suggest that patients with a combined ACL tear/untreated Segond fracture can have comparable outcomes to patients with an ACL tear and no Segond fracture when treated with ACLR alone.

Lingual Tonsil Hypertrophy in Patients With Allergic Rhinitis

2019 ◽  
Vol 34 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Kübra Çoban ◽  
Alper Köycü ◽  
Erdinc Aydın
Keyword(s):  
Allergic Rhinitis ◽  
Healthy Volunteers ◽  
Laryngopharyngeal Reflux ◽  
Control Group ◽  
Study Group ◽  
Positive Skin ◽  
Lingual Tonsil ◽  
Immunglobulin E ◽  
Skin Prick Tests ◽  
Grade 3

Background Lingual tonsils, part of the Waldeyers’ Ring, are located in base of the tongue. They are commonly observed in childhood, due to increased immunological activity. Several factors such as laryngopharyngeal reflux, younger age, smoking, and obesity are associated with hypertrophy of lingual tonsils (LTH) in adulthood. However, the relation between allergic rhinitis and LTH is not clearly highlightened in the literature so far. Objective To investigate the role of allergic rhinitis in the development of LTH. Methods Adult patients who were diagnosed with allergic rhinitis were included in the study group. The control group consisted of age- and sex-match healthy volunteers. Complete otorhinolaryngology examination including fiberoptic endoscopic evaluation was performed to both groups. Blood samples were obtained for total immunglobulin E levels, and skin prick tests were performed to both groups. Patients with allergy complaints and positive skin prick tests were included in the study group, while healthy volunteers with negative skin prick tests were enrolled in the control group. The grading for LTH was achieved by a physician who was blind to the study. Results The incidence of LTH was significantly higher in the study group when compared to the control group ( P = .001). Similarly, the incidence of grade 3 LTH was significantly higher in the study group compared to the controls ( P = .002). Conclusion According to our results, LTH is more frequently observed in patients with allergic rhinitis. Grade 3 representing larger LTH is more commonly seen in patients with allergic rhinitis.

scholarly journals Oral Hygiene in a Sample of Children/Adolescents Living in Family-Homes from the Province of Milan (Italy): A Pilot Study

2020 ◽  
Vol 8 (2) ◽  
pp. 33 ◽  
Author(s):  
Alessandro Nota ◽  
Floriana Bosco ◽  
Shideh Ehsani ◽  
Francesca Giugliano ◽  
Giulia Moreo ◽  
...  
Keyword(s):  
Pilot Study ◽  
Oral Hygiene ◽  
Clinical Results ◽  
Plaque Index ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Study Group ◽  
Significant Difference ◽  
And Gender ◽  
Oral Hygiene Instructions

Objective: This pilot study is a prospective controlled clinical trial, designed to evaluate the short-term clinical results (the plaque index) of an educational/motivational program for home oral hygiene, directed to children and adolescents who live in family-homes. Methods: The setting of the project was the province of Milan (Italy), where two family-homes were selected. The study group included 26 children (16 females and 10 males) aged between 7 and 15 years, of Italian nationality, from the family-home communities. The control group included 26 children (15 females and 11 males, aged between 7 and 15 years) of Italian nationality, matched for age and gender distribution with the study group, that were not in a socially disadvantaged condition. Collection of the plaque index (PI) was performed at t0. Then, all basic oral hygiene instructions were given to all children/adolescents and their educators. Education and motivation were repeated in the same way after 4–7 weeks (T1), and after 10–12 weeks (T2). The PI was taken also at T1 and T2. Results: An improvement in the PI was generally found in both groups, but there was no statistically significant difference between the two groups over time. Multivariate analysis of variance (MANOVA) revealed a statistically significant effect of time [F (1, 52) = 90.73, p < 0.001], regardless of the assignment group, in consequence of which the plaque index presented a moderate and significant improvement. Conclusion: The present data confirm the validity of the educational/motivational program to improve oral hygiene in children/adolescents, regardless of the assignment group.

scholarly journals Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer

2019 ◽  
Vol 3 (12) ◽  
pp. 2295-2304 ◽  
Author(s):  
Lia Head ◽  
Katja Kiseljak-Vassiliades ◽  
Toshimasa J Clark ◽  
Hilary Somerset ◽  
Jonathan King ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Standard Of Care ◽  
Response Evaluation ◽  
Adrenocortical Cancer ◽  
First Line ◽  
Current Standard ◽  
Dismal Prognosis ◽  
Grade 3 ◽  
Combined Immunotherapy ◽  
First Line Treatment

Abstract Adrenocortical carcinoma (ACC) is a rare orphan disease with a dismal prognosis. Surgery remains the first-line treatment, but most patients eventually develop metastatic disease. Mitotane is often used with chemotherapy with modest success. Little information is available concerning the efficacy of immunotherapy in combination with mitotane. We conducted a retrospective review of our initial six patients with metastatic ACC, for whom mitotane alone or with chemotherapy failed, and who were subsequently treated with a combination of pembrolizumab and mitotane, between July 2016 and March 2019. Imaging was analyzed per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Two patients had a partial response and four patients had stable disease (8 to 19 months). One patient had grade 3 hepatitis and pembrolizumab was discontinued after 8 months. She died with disease progression 16 months after initiating pembrolizumab. One patient developed brain metastasis after 19 months of treatment and was transitioned to hospice. One patient had focal pneumonitis after 18 months of treatment, and pembrolizumab was discontinued. Three remaining patients continue pembrolizumab plus mitotane at the time of this writing. The current standard of care for ACC is a combination of etoposide, doxorubicin, cisplatin, and mitotane with an overall survival of 14.8 months. All six patients lived for at least 16 months after starting pembrolizumab added to mitotane therapy. The therapy appeared to be effective in both microsatellite instability-high and microsatellite stable tumors, suggesting some synergistic effect with mitotane. Combined immunotherapy and mitotane should be considered in future clinical trials in patients with ACC.

Analyzing a Health-System's Use of Unfractionated Heparin to Ensure Optimal Anticoagulation

2005 ◽  
Vol 21 (2) ◽  
pp. 69-77 ◽  
Author(s):  
Samantha P Jellinek ◽  
Victor Cohen ◽  
Antonios Likourezos ◽  
William M Goldman ◽  
Eustace L Lashley
Keyword(s):  
Decision Support ◽  
Unfractionated Heparin ◽  
Medical Literature ◽  
Standard Of Care ◽  
Control Group ◽  
Computerized Physician Order Entry ◽  
Order Entry ◽  
Current Standard ◽  
Dosing Strategy ◽  
Physician Order Entry

Background: Although unfractionated heparin (UH) dosing nomograms have proven to be superior to standard dosing, the latter remains the mainstay at our institution. We hypothesize that the incorporation of technology integrated with a decision support algorithm will facilitate the use of a UH nomogram by clinicians. Objective: To critically appraise the steps involved with the use of UH, create a decision support algorithm to aid in the management of UH, and determine whether the use of this algorithm can improve achievment of rapid and safe anticoagulation compared with the current standard of care. Methods: We analyzed the steps involved with the use of UH and subsequently reviewed the medical literature for risk factors for bleeding that patients may harbor when initiating UH. Based on this information, we designed a computerized physician order entry (CPOE), factor-based, weight-adjusted decision support algorithm with the primary goal of minimizing the risk of bleeding while optimizing and ensuring optimal anticoagulation. We compared the CPOE strategy with our current standard of care. Results: The CPOE factor–based dosing strategy significantly improved the rates and decreased the time to achieving an initial activated partial thromboplastin time (aPTT) that was ≥60 seconds compared with the control group. At the time of first aPTT measurement, the CPOE factor-based group achieved a 92.9% therapeutic rate compared with the standard heparin dosing group, which achieved a 60.8% therapeutic rate (p < 0.01). Conclusions: The institution of a CPOE factor-based dosing strategy in collaboration with pharmacists' interventions optimizes anticoagulation treatment with UH.

scholarly journals Effect of Rifampin on Steady-State Pharmacokinetics of Atazanavir with Ritonavir in Healthy Volunteers

2006 ◽  
Vol 50 (10) ◽  
pp. 3336-3342 ◽  
Author(s):  
D. M. Burger ◽  
S. Agarwala ◽  
M. Child ◽  
A. Been-Tiktak ◽  
Y. Wang ◽  
...  
Keyword(s):  
Steady State ◽  
Standard Of Care ◽  
Hiv Protease ◽  
Control Group ◽  
Hiv Protease Inhibitors ◽  
Time Curve ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
Dosing Regimens ◽  
Grade 3

ABSTRACT Mycobacterium tuberculosis is a concern in patients with human immunodeficiency virus (HIV) infection. Rifampin (RIF), an agent used against M. tuberculosis, is contraindicated with most HIV protease inhibitors. Atazanavir (ATV) has clinical efficacy comparable to a standard of care regimen in naive patients and, when dosed with low-dose ritonavir (RTV), also in treatment-experienced patients. We evaluated here the safety and pharmacokinetics of ATV, resulting from three regimens of ATV, RTV, and RIF in 71 healthy subjects. The pharmacokinetics for ATV and RTV were assessed after 6 and 10 days of dosing with ATV 400 mg (n = 53) and with ATV-RTV at 300 and 100 mg (ATV/RTV 300/100; n = 52), respectively. Steady-state pharmacokinetics for ATV, RTV, RIF, and desacetyl-rifampin (des-RIF) were measured after 10 days of dosing of ATV/RTV/RIF 300/100/600 (n = 17), ATV/RTV/RIF 300/200/600 (n = 17), or ATV/RTV/RIF 400/200/600 (n = 14). An RIF 600-alone arm was enrolled as a control group (n = 18). With ATV/RTV/RIF 400/200/600, ATV area under the concentration-time curve values were comparable, but the C min values were lower relative to ATV 400 alone. ATV exposures were substantially reduced for the other RIF-containing regimens relative to ATV 400 alone and for all regimens relative to ATV/RTV 300/100 alone. RIF and des-RIF exposures were 1.6- to 2.5-fold higher than with RIF 600 alone. The incidence of grade 3/4 alanine aminotransferase/aspartate aminotransferase values was limited to 1 subject each in both the ATV/RTV/RIF 300/200/600 and the ATV/RTV/RIF 400/200/600 treatments. Coadministration of ATV with RIF was safe and generally well tolerated. Since ATV exposures were reduced in all regimens, ATV and RIF should not be coadministered at the dosing regimens studied.

Intensive Consolidation with Clofarabine and Intermediate-Dose Cytarabine (CLARA) in Patients with High-Risk AML in First CR: The ALFA-0702 Pilot Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1934-1934 ◽  
Author(s):  
Xavier Thomas ◽  
Ida Lobe ◽  
Emmanuel Raffoux ◽  
Nicolas Boissel ◽  
Quoc-Hung Le ◽  
...  
Keyword(s):  
Pilot Study ◽  
High Risk ◽  
Median Time ◽  
Remission Induction ◽  
High Dose ◽  
Antibacterial Prophylaxis ◽  
Younger Adults ◽  
Historical Series ◽  
Grade 3 ◽  
Intermediate Dose

Abstract Introduction. One standard option for consolidation chemotherapy in younger patients with acute myeloid leukemia (AML) in first CR (CR1) is based on 3 to 4 repeated cycles of high-dose cytarabine (HDAC), according to the CALGB schedule (RJ. Mayer, NEJM 1994). Nevertheless, relapse incidence remains high, especially in those with high-risk AML features and no available donor for allogeneic stem cell transplantation (SCT). Combination of clofarabine with intermediate-dose cytarabine (CLARA) has been reported to induce promising response rate in high-risk AML patients (S. Faderl, Blood 2005 and 2006). We thus tested the feasibility and safety of CLARA consolidation in these patients. Methods. In this 2-center ALFA-0702 pilot study, all younger adults with high-risk AML in CR1 and no possibility of conventional SCT were eligible to receive three CLARA cycles. Patients with good-risk AML (core binding factor, NPM1+/FLT3-ITDwt, or CEBPA+/FLT3-ITDwt) were not eligible and received standard HDAC consolidation. Each CLARA cycle consisted of 1,000 mg/m2/d cytarabine day 1–5 and 40 mg/m2/d clofarabine day 2–6. Planned interval between two consecutive cycles was 35 days. All patients received oral antibacterial prophylaxis with amoxicillin or levofloxacin. Results. Between February 2007 and July 2008, 19 patients aged 22 to 63 years (median, 48 years) were enrolled. All had previously received remission induction according to ALFA protocols. At diagnosis, cytogenetic and molecular findings were as follows: FLT3-ITD (#6), abns of chromosome 5 or 7 (#3), complex karyotype (#1), 3q abn (#1), t(6;9) (#1), 11q23 abn (#1), normal karyotype or various abns (#6). At the present time, a total of 37 CLARA cycles are evaluable for safety. Myelosuppression was relatively rapid and profound. The median time to reach a PMN count less than 0.5 x 109/L was 8 days (range, 6–11). All cycles required platelet transfusions. The median time from cycle initiation to neutrophil recovery (≥ 0.5 x 109/L) was 28 days (range, 17–48), without differences between cycles 1, 2, or 3. However, probably due to non-hematological events, the median time between two consecutive cycles was 43 days (range, 39–79) between cycle 1 and 2, and 48 days (range, 42–78) between cycle 2 and 3. Main clinically relevant non-hematologic toxicities were sepsis (#14), Grade 3/4 nausea/vomiting (#13), Grade 3/4 mucositis (#4), and fungal (#3) or VZV (#1) infection. One patient experienced a curious unexpected and transient CNS event with a mixed sensitive-motor unilateral presentation and cervical hypersignal at MRI. One patient died from a septic shock after the second cycle. Three patients received only two cycles because of an adverse event (fungal infection, liver toxicity, CNS toxicity). Two additional patients received reduced intensity conditioning SCT after one and two CLARA cycles, respectively. Both are alive in CR1 six and four months after SCT, respectively. Even if the follow-up is still relatively short (median, 7 months), only one patient relapsed after 11 months of CR1 duration (the one with t(6;9) translocation). When compared to a historical series of 28 CR patients with similar eligibility criteria treated in the previous ALFA-9802 trial by HDAC consolidation, a gain in disease-free survival might appear (estimated 12-month DFS, 75 versus 57%). Conclusion. Administration of repeated CLARA consolidation cycles is feasible in younger adults with AML in CR1. However, the high rate of infections leads to recommend a careful patient monitoring maximizing infectious prophylaxis and avoiding out-patient management. The randomized ALFA-0702 Phase 2 trial will be initiated in Q4 2008 by the ALFA group in order to prospectively compare these two consolidation approaches in terms of anti-leukemic efficacy.

A Direct Comparison of High Dose Cytarabine to Combination of Gemtuzumab and High Dose Cytarabine for Acute Myeloid Leukemia Patients in First Relapse Confirmed the Benefit of Gemtuzumab Based Regimens.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2051-2051
Author(s):  
Thomas Prébet ◽  
Aude Charbonnier ◽  
Anne Etienne ◽  
Evelyne D'Incan ◽  
Sabine Fürst ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Standard Of Care ◽  
Allogeneic Transplantation ◽  
Control Group ◽  
High Dose ◽  
Current Standard ◽  
Advanced Phase ◽  
High Dose Cytarabine ◽  
First Relapse

Abstract Abstract 2051 Poster Board II-28 Acute meyloid leukemia (AML) in first relapse is associated with a poor outcome when treated with standard dose cytarabine regimens and intermediate to high dose cytarabine (IHDAraC) is the current standard of care. During the last years, Gemtuzumab Ozogamycin (GO) has demonstrated a relevant clinical activity in relapsed and refractory AML. This antibody directed against CD33 is conjugated to calicheamycin that triggers apoptosis when hydrolyzed in the leukemic blasts. Combination regimen of GO are currently extensively studied in both frontline and advanced phase disease. Nevertheless, analysis of the litterature showed that only few data are available regarding a direct comparison of IHDAraC and IHDAraC+GO regimen. To this respect, we conduced a retrospective analysis of response (CR and CRi) and survival for patients with first relapse AML treated in our centre with either IHDAraC or IHDAraC+GO regimen. A total of 84 patients were included in the analysis: 28 were induced in the IHDAraC+GO group (mean GO dose: 6mg/m2, range:[3-9], including 82% of combination with anthracyclines or etoposide) and 56 in the IHDAraC group (including 57% of combination with other agents, mostly etoposide and anthracyclines). Patients characteristics were comparable between the IHDAraC+GO group and the control group in terms of median age (51y vs 49y), Performance Status at relapse (1 vs 1), median time to relapse (221 days vs 280 days), cytogenetic risk group clustering and previous allogeneic transplantation in first CR (21% vs 16%). Median Follow-up was 24 months. Univariate analysis showed that IHDAraC+GO induction, as compared with IHDAraC, was associated with a better response rate (68% vs 48%, p=0.08), a lower relapse rate (31% vs 66%, p=0.02), a better Overall Survival (median 35 months vs 19 months, p=0.02) and a better Event Free Survival (median Not Reached vs 10 months, p=0.02). Of note, the better response rate in the IHDAraC+GO group allowed to bring more patients to allogeneic transplantation in second CR (33% vs 16% respectively, p=0.08).Multivariate analysis using logistic regression method for response evaluation and Cox model for survival showed that treatment in the IHDAraC+GO group was an independent prognosis factor with a favorable impact on both response (HR:2.8, 95%CI:[1.1-7.7], p=0.048) and Overall Survival (HR:1.9, 95%CI:[1.1-3.4], p=0.047). It is already known that combination of IHDAraC and GO could give good results for advanced phase AML patients but, to our knowledge, this report is the first that directly compared the results of IHDAraC+GO with the current standard of care regimen on an homogeneous sample of patients in first relapse. This report also underline the importance of a prospective comparison in order to define the best combination therapy. Disclosures: No relevant conflicts of interest to declare.

A Clinical Pharmacology and Exploratory Study of Azacitidine Administered Subcutaneously or Intravenously In Japanese Patients with Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4964-4964
Author(s):  
Yukio Kobayashi ◽  
Michinori Ogura ◽  
Kiyoshi Ando ◽  
Kensei Tobinai ◽  
Toshiki Uchida ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Median Time ◽  
Research Funding ◽  
Treatment Protocol ◽  
Japanese Patients ◽  
Hematologic Response ◽  
Transfusion Requirements ◽  
Grade 3 ◽  
To Receive

Abstract Abstract 4964 [Background and Purpose]: Azacitidine is a pyrimidine nucleoside analog of cytidine with hypomethylating and cytotoxic activity. Although azacitidine is currently approved for subcutaneous (SC) injection and intravenous(IV) administration for the treatment of myelodysplastic syndromes (MDS) in the US, there are limited data available on the treatment effects of IV versus SC administration. To compare the safety, pharmacokinetics (PK), and efficacy of IV with SC administration, a phase I/II study of azacitidine in Japanese patients with MDS was conducted. [Patients and Method]: Patients with RA, RA with ringed sideroblasts (RARS), RAEB, or RAEB-t defined by the French-American-British (FAB) classification were enrolled. RA and RARS must fulfill the additional criteria of significant marrow dysfunction (defined by cytopenias and/or transfusion requirements). Eligible patients were at least 20 years of age but younger than 80 and had a ECOG PS between 0 and 2. The patients were alternately assigned to receive azacitidine SC or IV (10-minutes) at 75 mg/m2/day for 7 days every 4 weeks for a minimum of 4 cycles. Patients who achieved a complete response (CR) received additional 3 cycles of azacitidine and were followed up without treatment. Subjects with a partial response (PR) or hematologic improvement (HI) received azacitidine until disease progression with a maximum of 18 cycles. Ten patients received azacitidine by both SC and IV administration on the different cycle and PK parameters were compared on day 1 of each cycle. The primary endpoints of this study were the safety, PK and HI according to the International Working Group (IWG 2006) criteria for MDS, respectively. [Results]: A total of 54 patients (10 in phase I portion and 44 in phase II portion) were enrolled between October 2007 and November 2008. Of these, 53 patients received at least one dose of azacitidine; 17 patients (32 %) were female; the median age was 65 years (range 35–77 years). FAB MDS subtypes were: RA (16/53, 30%); RARS (3/53, 6%); RAEB (20/53, 38%); RAEB-t (14/53, 26%). IPSS risk groups were: Low (0%); Int-1(23/53, 43%); Int-2(15/53, 28%); High(15/53, 28%). IPSS cytogenetic groups were: good (24/53, 45%); intermediate (13/53, 25%); poor (16/53, 30%). Fifty-one patients have completed the treatment protocol to date. The median number of treatment cycles was 7(range 1 – 18). Seven patients have completed 18 cycles of treatment. Two patients are continuing to receive treatment in their cycles 16 and 17. HI was observed in 53% (26/49) of patients. Median time to HI was 55 days (range 20–217). Of the 27 patients who were RBC transfusion dependent at baseline, 15 (56%) became transfusion independent. Hematologic response (CR, PR, or marrow CR) was achieved in 29% (15/51) of patients. Median time to hematologic response was 113 days (range 49–247). HI rate in SC and IV administration was 50 % (12/24) and 56 % (14/25), respectively. Hematologic response rate in SC and IV administration was 29% (7/24) and 30% (8/27), respectively. There were no significant differences between SC and IV administration of azacitidine for HI and hematologic response. The Cmax following IV administration was approximately 4-fold of that obtained following SC administration; however, the AUC(0-∞) following SC administration was 92.3 ± 15.8% compared to that of IV, indicating good bioavailability following SC administration. Overall, the PK profile was similar to that of the previously reported study. The most common grade 3 or 4 adverse events included neutropenia 80% (41/51), leukopenia 76% (39/51), hemoglobin decreased 71% (36/51) and thrombocytopenia 65% (33/51). Grade 3 or 4 non-hematologic adverse events which were observed more than 10% included pneumonia 12% (6/51) and hypophosphatemia 16%(8/51). There was no death during the study that occurred within 29 days of last dose of azacitidine. The safety profile did not differ significantly different between SC and IV administration with the exception of injection site reactions observed with SC administration, only. [Conclusions]: Azacitidine is generally well tolerated and demonstrated a beneficial effect in Japanese patients with MDS. The higher Cmax of IV dose was not translated into clinical outcomes; no difference was shown in both efficacy and safety profiles between SC and IV administration. Both IV and SC azacitidine are promising therapeutic options for Japanese patients with MDS. Disclosures: Kobayashi: Nippon Shinyaku Co., Ltd.: Research Funding. Ogura: Nippon Shinyaku Co., Ltd: Research Funding. Ando: Nippon Shinyaku Co., Ltd.: Research Funding. Tobinai: Nippon Shinyaku Co., Ltd.: Research Funding. Uchida: Nippon Shinyaku Co., Ltd.: Research Funding. Ogawa: Nippon Shinyaku Co., Ltd.: Research Funding. Ishikawa: Nippon Shinyaku Co., Ltd.: Research Funding. Ohashi: Nippon Shinyaku Co., Ltd.: Research Funding. Hata: Nippon Shinyaku Co., Ltd.: Research Funding. Usui: Nippon Shinyaku Co., Ltd.: Research Funding. Taniwaki: Nippon Shinyaku Co., Ltd.: Research Funding. Ohnishi: Nippon Shinyaku Co., Ltd.: Research Funding. Akiyama: Nippon Shinyaku Co., Ltd.: Research Funding. Ozawa: Nippon Shinyaku Co., Ltd.: Research Funding. Ohyashiki: Nippon Shinyaku Co., Ltd.: Research Funding. Okamoto: Nippon Shinyaku Co., Ltd.: Research Funding. Tomita: Nippon Shinyaku Co., Ltd.: Research Funding. Nakao: Nippon Shinyaku Co., Ltd.: Research Funding. Hotta: Nippon Shinyaku Co., Ltd.: Research Funding.

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