A Randomized Crossover Study of High- and Standard-Dose Recombinant Factor VIIa for Treatment of Hemarthroses in Hemophiliacs with Inhibitors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 323-323
Author(s):  
Elena Santagostino ◽  
Maria E. Mancuso ◽  
Angiola Rocino ◽  
Giacomo Mancuso ◽  
Francesco A. Scaraggi ◽  
...  
Keyword(s):  
Dose Regimen ◽  
Factor Viia ◽  
Standard Dose ◽  
Home Treatment ◽  
Response To Treatment ◽  
High Dose ◽  
Success Rates ◽  
Recurrence Rates ◽  
High Dose Regimen ◽  
Vas Score

Abstract A multicenter randomized crossover trial was designed to compare efficacy, safety, feasibility and cost associated with standard- and high-dosages of rFVIIa for home treatment of hemarthroses in hemophiliacs with inhibitors. Enrolled patients were instructed to treat within 6 hours from the onset of bleeding 4 consecutive haemarthroses of ankles, knees or elbows either with the rFVIIa standard dose of 90 mcg/kg (repeated as necessary every 3 hours) or with a single high dose of 270 mcg/kg. Patients who did not achieve a success within 9 hours continued rFVIIa treatment with repeated standard doses. The response to treatment was assessed for up to 48 hours by patients/caregivers who reported on a visual analogic scale (VAS) graded from 0 to 100 the improvement in symptoms and also rated the response as effective, partially effective or ineffective. Success was defined a treatment rated as effective and VAS score ≥70 and failure a treatment rated as ineffective and VAS score ≤30, responses that did not fulfil these criteria being considered a partial response. Of 20 hemophiliacs with inhibitors enrolled (median age: 27 years), 18 treated 32 hemarthroses assigned to the standard- and 36 to the high-dose regimen during the study period of 18 months. Forty-eight hemarthroses (71%) occurred in target joints. Success rates for standard- and high-dose regimens were similar: 31% and 25% at 9 hours, 53% and 50% at 24 hours, 66% and 64% at 48 hours. Recurrence rates were identical (3%). The median number of rFVIIa boluses needed to achieve a successful course was 3 for the standard-dose and 1 for the high-dose regimen, and the median amount of rFVIIa used per successful course was identical (270 mcg/kg). Our results indicate that the use of a high-dose regimen with rFVIIa for home treatment of hemarthroses is effective, safe, does not imply an increased consumption of rFVIIa and requires the infusion of a smaller number of boluses. Its convenience is particularly relevant in cases with difficult venous access and in hemorrhages into target joints.

Efficacy and Safety of Tigecycline for Patients with Hospital-Acquired Pneumonia

Chemotherapy ◽  
2016 ◽  
Vol 61 (6) ◽  
pp. 323-330 ◽  
Author(s):  
Li Xu ◽  
Ya-Li Wang ◽  
Shuai Du ◽  
Lin Chen ◽  
Li-Hui Long ◽  
...  
Keyword(s):  
Dose Regimen ◽  
Clinical Cure ◽  
Standard Dose ◽  
Meta Analysis ◽  
High Dose ◽  
Efficacy And Safety ◽  
High Dose Regimen ◽  
Significant Difference ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

Background: Tigecycline is an antibiotic agent with a broad spectrum, which has an antibacterial effect against many multidrug-resistant organisms. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is disputed. Materials and Methods: In this report, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of tigecycline for the treatment of HAP. The primary outcome was the rate of clinical cure, and the secondary outcomes were mortality and adverse events (AEs). Results: Four trials involving 1,234 patients were included. The standard-dose tigecycline and comparator groups did not differ significantly in their rates of clinical cure. However, high-dose tigecycline was more effective than standard-dose tigecycline or the comparators for the treatment of HAP. There was no significant difference in mortality between the standard-dose or high-dose regimen and the comparators. Although the safety profile of standard-dose tigecycline was similar to the comparators, the high-dose regimen exhibited more AEs compared with the other groups. Conclusion: High-dose tigecycline is efficient for the treatment of HAP but is associated with more AEs.

Randomized Phase III Study Comparing Conventional-Dose Doxorubicin Plus Ifosfamide Versus High-Dose Doxorubicin Plus Ifosfamide Plus Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Advanced Soft Tissue Sarcomas: A Trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group

2000 ◽  
Vol 18 (14) ◽  
pp. 2676-2684 ◽  
Author(s):  
A. Le Cesne ◽  
I. Judson ◽  
D. Crowther ◽  
S. Rodenhuis ◽  
H.J. Keizer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Dose Regimen ◽  
Standard Dose ◽  
Soft Tissue Sarcomas ◽  
Dose Intensity ◽  
High Dose ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Grade 3 ◽  
Stimulating Factor

PURPOSE: This randomized multicenter study was designed to compare the activity of a high-dose doxorubicin-containing chemotherapy regimen with a conventional standard-dose regimen in adult patients with advanced soft tissue sarcomas (ASTS). PATIENTS AND METHODS: Between 1992 and 1995, 314 patients were randomized to receive a standard-dose regimen (arm A), containing doxorubicin (50 mg/m2 on day 1) and ifosfamide (5 g/m2 on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m2 on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 μg/m2 on days 3 to 16); all courses were repeated every 3 weeks. RESULTS: The median age of the 294 eligible patients was 50 years. They received a median of five chemotherapy cycles. The median dose and relative doxorubicin dose-intensity achieved were 245 mg and 97% in arm A and 360 mg and 99% in arm B, respectively. Thirty-eight percent and 23% of patients presented with leiomyosarcomas and liver metastases, respectively. Objective responses were observed in 31 (21%) of 147 assessable patients in arm A and in 31 (23.3%) of 133 in arm B (P = .65). No change was observed in 41.6% and 46.2% of patients in arm A and B, respectively. Progression-free survival (PFS) was significantly longer in the intensive arm (P = .03). The median duration of the time to progression was 19 weeks in the conventional arm and 29 weeks in the intensified arm. There was no difference in overall survival (P = .98) between the two therapeutic arms. Toxicities were manageable in both arms. A grade 3/4 neutropenia and infection occurred in 92% and 4.6% of patients in arm A, respectively, and in 90% and 16.6% in arm B, respectively. Grade 3/4 thrombocytopenia was more frequent in arm B. CONCLUSION: The use of rhGM-CSF allowed safe escalation of chemotherapy doses. Despite a 50% increase of the doxorubicin dose-intensity, the high-dose regimen failed to demonstrate any impact on survival in patients with ASTS. The low complete response rate, the high incidence of leiomyosarcomas, and liver metastases may in part explain these results. However, the lengthening of the PFS in the intensive arm, because of the quality of stable disease and inappropriate tumor evaluation policies that potentially lead to an underestimation of antitumor activity, does not definitively refute the use of a high-dose chemotherapy regimen in selected patients with ASTS.

A randomized trial of standard chemotherapy v a high-dose chemotherapy regimen in the treatment of poor prognosis nonseminomatous germ-cell tumors.

1988 ◽  
Vol 6 (6) ◽  
pp. 1031-1040 ◽  
Author(s):  
R F Ozols ◽  
D C Ihde ◽  
W M Linehan ◽  
J Jacob ◽  
Y Ostchega ◽  
...  
Keyword(s):  
Germ Cell ◽  
Dose Regimen ◽  
Standard Therapy ◽  
Poor Prognosis ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
High Dose Regimen ◽  
Disease Free

We performed a prospective randomized trial of a high-dose chemotherapy regimen v standard cisplatin-based chemotherapy in poor prognosis nonseminomatous germ-cell cancer patients. The high-dose regimen consisting of twice the standard dose of cisplatin (P), along with vinblastine (Ve), bleomycin (B), and the epipodophylotoxin etoposide (VP-16) (V) (PVeBV) was compared to the classic regimen with normal dose cisplatin, vinblastine, and bleomycin (PVeB). Eligibility criteria included large abdominal masses, liver metastases, multiple pulmonary metastases, brain metastases, marked elevations in serum tumor markers (alpha-fetoprotein greater than 1,000 ng/mL or the beta-subunit of human chorionic gonadotropin greater than 10,000 mIU), unfavorable histology (pure choriocarcinoma), or extragonadal germ-cell tumors. Fifty-two consecutive patients with poor prognostic features were randomized to receive either PVeBV or PVeB. The median follow-up is 4 years. Treatment with the high-dose regimen increased the complete remission rate (88% v 67%, P = .14) and was associated with a lower relapse rate (17% v 41%, P = .2). The median survival of patients receiving standard therapy was 30 months, while the median survival for patients receiving the high-dose regimen has not been reached. Actuarial 5-year survival for patients treated with the high-dose regimen is 78%, compared with 48% for patients receiving standard therapy (two-sided Mantel-Cox test = .06). Disease-free survival was also superior for patients randomized to PVeBV (P = .03). Sixty-eight percent of patients (23 of 34) randomized to PVeBV are alive and continuously disease-free, compared with 33% (six of 18) for PVeB (P = .02). The major difference in toxicity between the high-dose regimen and standard therapy was the severity of myelosuppression and the incidence of severe hearing loss. Ninety-one percent of patients treated with PVeBV had a WBC count less than 1,000/microL, compared with 50% of patients receiving PVeB (P less than .05). Hearing aids were recommended for 12 patients who received PVeBV and two who received PVeB. The increased effectiveness of the PVeBV regimen in poor prognosis germ-cell cancer patients may relate to the double-dose cisplatin, the addition of VP-16, or to a synergistic effect of these two drugs.

Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.

1988 ◽  
Vol 6 (9) ◽  
pp. 1491-1500 ◽  
Author(s):  
A E Chang ◽  
T Kinsella ◽  
E Glatstein ◽  
A R Baker ◽  
W F Sindelar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Dose Regimen ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Regimen ◽  
Disease Free

We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.

Genetic Polymorphisms Associated with Clinical Outcome in the Intergroup Trial S9321, Comparing High Dose Therapy with Standard Dose Therapy for Myelomaon, on Behalf of ECOG, SWOG, CALGB, and the Bank on a Cure.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1495-1495
Author(s):  
Rafael Santana-Davila ◽  
John Crowley ◽  
Brian Durie ◽  
Bart Barlogie ◽  
Philip Greipp ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Genetic Polymorphisms ◽  
Median Survival ◽  
Dose Regimen ◽  
Standard Dose ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Intergroup Trial

Abstract Genetic variations in patient populations likely contribute to disease progression and therapeutic outcomes. We have begun a systematic approach to examine the association of genetic variations (ie. functional, single nucleotide polymorhisms, SNPs) involved in myeloma growth promotion, metabolic events, drug responses, and DNA repair on clinical outcome in the intergroup trial S9321. This trial tested a single high dose regimen with autologous stem cell support against a conventional dose regimen, with further randomization of responders to maintenance with interferon or not, in newly diagnosed patients with multiple myeloma. ECOG, CALGB and SWOG enrolled 899 patients with newly diagnosed MM to receive VAD induction x 4 cycles followed by randomization to PBSC-supported high dose therapy (HDT) versus standard dose therapy (SDT) of VBMCP, using CTX 4.5 g/m2 + G-CSF for PBSC mobilization in all patients. Responders to VBMCP or HDT were randomized to IFN or no maintenance. Specimens were distributed through ECOG for biologic correlative studies, including candidate SNP analysis. SNP assays have been developed using the Sequenom Mass-extend platform for functional SNPs in IL-6, IL-1, IL-RA, IL-10, TNF, Lta, TGFb, MDR1, MPO, CYP3A4, GST (M, P, T), ERCC2 and XRCC1, and are being evaluated on 803 DNA samples prepared from patients enrolled in S9321. Preliminary findings (n=135) demonstrate functional genetic variants of IL-10 (position -1082), IL-1 (position +3953), TGFb (postion -509), and TNFa (position -308) are showing trends associated with differences in progression free survival; and variants in IL-6 (position -174) are associated with response. Median survival of the IL-10 variants was 31 months for A/A low producer alleles versus 19 months for the G/G high producer alleles (p=.5). For TNFa, 2 cases with the high producer A/A alleles died within a year, while the median survival for the lower producer G/G alleles was 2 years (p=.04). For patients with the high producer C/C/ allele of IL-1 (n=67), median survival was 2 years, versus 5 patients with the T/T low producer alleles that had a median survival greater than 5 years (preliminary p=.29). While these preliminary results are now only suggestive of trends in genetic polymorphisms associated with clinical outcome, completion of the full SNP panel on the entire sample base should provide a extensive association study, and analysis of potential differences in therapy arms of the trial. The full panel and association studies will be presented.ααββααα

Autologous Stem Cell Transplantation (autoSCT) for HIV-Associated Lymphoma in the Era of Combination Antiretroviral Therapy (cART): A Retrospective Analysis of the EBMT Lymphoma Working Party

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2257-2257 ◽  
Author(s):  
Kai Huebel ◽  
Alessandro Re ◽  
Ariane Boumendil ◽  
Herve Finel ◽  
Marcus Hentrich ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Dose Regimen ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Hiv Patients ◽  
High Dose Regimen

Abstract Introduction: Patients infected with HIV have an increased risk of developing aggressive B-cell non-Hodgkin lymphoma and Hodgkin lymphoma (HL). The continuous development of cART during the last decade has improved the prognosis of HIV-associated lymphoma considerably. However, a significant proportion of these patients will experience lymphoma relapse and may be candidates for autoSCT. The purpose of the present study was to investigate if recent advances in anti-lymphoma therapy and anti-infectious strategies have influenced the outcome of autoSCT for HIV-related lymphoma. Patients and methods: For this retrospective study, all EBMT-registered patients aged 18 years or older with HIV-positive serostatus who were treated with a first autoSCT between 2007 and 2013 were eligible. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers were requested to provide additional HIV and lymphoma treatment and follow-up information. Statistical analysis used log rank test to assess the impact of baseline characteristics on survival endpoints. In multivariate analysis, the relevance of prognostic factors was estimated using Cox regression models. Curves of cumulative incidence of relapse (IR) and non-relapse mortality (NRM) were compared by Gray's test. Results: 138 patients from 25 European centers met the eligibility criteria and had the full data set required for this analysis available. 86% were male, median age was 44 years (range 24-69). Underlying diagnoses were diffuse large B cell lymphoma (DLBCL) in 46%, HL in 21%, Burkitt lymphoma in 14%, plasmablastic lymphoma (PBL) in 10%, and other lymphoma in 9% of the patients. Disease status at autoSCT was complete remission (CR) in 51%, partial remission (PR) in 33%, and less than PR in 16% of the patients, achieved after 1 (28%), 2 (58%), or more than 2 lines of chemotherapy (14%). With HIV load below the threshold of detection in 74% of the patients, the median CD4+ cell count was 187/µl (range 0-800) at transplant. 95% of the patients continued with cART during salvage and high-dose chemotherapy. BEAM was used as high-dose regimen in 77% of the patients. With a median follow-up of 4 years, 2-year NRM, IR, progression-free survival (PFS) and overall survival for the whole series were 9%, 23%, 68% and 70%, respectively. By multivariate analysis, diagnosis DLBCL or PBL (vs HL), increasing number of chemotherapy pretreatment lines, and less than PR at autoSCT were significant predictors of an unfavorable PFS; whilst age, high-dose regimen, performance status, and viral load had no significant impact. 2-year PFS in patients with 1st-line CR, later CR, PR, or less than PR at autoSCT was 91%, 80%, 64%, and 23%, respectively. Conclusions: This series, which is the largest ever on lymphoma transplants in HIV+ patients, suggests that in the cART / chemoimmunotherapy era, the outcome of autoSCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of HIV infection. AutoSCT under ongoing cART therapy remains the treatment of choice for HIV+ patients with PBL or recurrent DLBCL or HL. Disclosures Kröger: Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Montoto:Roche: Honoraria; Gilead: Research Funding. Dreger:Novartis: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Gilead: Consultancy; Janssen: Consultancy; Roche: Consultancy.

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