scholarly journals Bamlanivimab reduces nasopharyngeal SARS-CoV-2 RNA levels but not symptom duration in non-hospitalized adults with COVID-19

2021 ◽  
Author(s):  
Kara W Chew ◽  
Carlee Moser ◽  
Eric S Daar ◽  
David A Wohl ◽  
Jonathan Z Li ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Area Under The Curve ◽  
Multicenter Trial ◽  
Inflammatory Biomarkers ◽  
Study Entry ◽  
Symptom Improvement ◽  
Symptom Duration ◽  
Risk Of Progression ◽  
Grade 3 ◽  
Rna Levels

Importance: The antiviral activity and efficacy of anti-SARS-CoV-2 monoclonal antibody (mAb) therapies to accelerate recovery from COVID-19 is important to define. Objective: To determine safety and efficacy of the mAb bamlanivimab to reduce nasopharyngeal (NP) SARS-CoV-2 RNA levels and symptom duration. Design: ACTIV-2/A5401 is a randomized, blinded, placebo-controlled platform trial. Two dose cohorts were enrolled between August 19 and November 17, 2020 for phase 2 evaluation: in the first, participants were randomized 1:1 to bamlanivimab 7000 mg versus placebo, and in the second to bamlanivimab 700 mg versus placebo. Randomization was stratified by time from symptom onset (≤ or >5 days) and risk of progression to severe COVID-19 ('higher' vs 'lower'). Setting: Multicenter trial conducted at U.S. sites. Participants: Non-hospitalized adults ≥18 years of age with positive SARS-CoV-2 antigen or nucleic acid test within 7 days, ≤10 days of COVID-19 symptoms, and with oxygen saturation ≥92% within 48 hours prior to study entry. Intervention: Single infusion of bamlanivimab (7000 or 700 mg) or placebo. Main Outcomes and Measures: Detection of NP SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28, time to improvement of all of 13 targeted COVID-19 symptoms by daily self-assessment through day 28, and grade 3 or higher treatment emergent adverse events (TEAEs) through day 28. Secondary measures included quantitative NP SARS-CoV-2 RNA, all-cause hospitalizations and deaths (composite), area under the curve of symptom scores from day 0 through day 28, plasma bamlanivimab concentrations, plasma and serum inflammatory biomarkers, and safety through week 24. Results: Ninety-four participants were enrolled to the 7000 mg cohort and 223 to the 700 mg cohort and initiated study intervention. The proportion meeting protocol criteria for 'higher' risk for COVID-19 progression was 42% and 51% for the 7000 and 700 mg cohort, respectively. Median time from symptom onset at study entry for both cohorts was 6 days. There was no difference in the proportion with undetectable NP SARS-CoV-2 RNA at any post-treatment timepoints (risk ratio compared to placebo, 0.82-1.05 for 7000 mg dose [overall p=0.88] and 0.81-1.21 for 700 mg dose [overall p=0.49]), time to symptom improvement (median of 21 vs 18.5 days, p=0.97, for 7000 mg bamlanivimab vs placebo and 24 vs 20.5 days, p=0.08, for 700 mg bamlanivimab vs placebo), or grade 3+ TEAEs with either dose compared to placebo. Median NP SARS-CoV-2 RNA levels were lower at day 3 and C-reactive protein, ferritin, and fibrinogen levels significantly reduced at days 7 and 14 for bamlanivimab 700 mg compared to placebo, with similar trends observed for bamlanivimab 7000 mg. Viral decay modeling supported more rapid decay with bamlanivimab compared to placebo. Conclusions and Relevance: Treatment with bamlanivimab 7000 mg and 700 mg was safe and compared to placebo led to more rapid reductions in NP SARS-CoV-2 RNA and inflammatory biomarkers, but did not decrease time to symptom improvement. The clinical utility of mAbs for outcomes other than hospitalizations and deaths is uncertain. Trial Registration: ClinicalTrials.gov Identifier: NCT04518410

A phase II multicenter trial of paclitaxel and carboplatin in women with advanced or recurrent malignant mixed müllerian tumors (MMMT) of the uterus

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5589-5589 ◽  
Author(s):  
L. M. Ramondetta ◽  
R. A. Lacour ◽  
E. D. Euscher ◽  
R. B. Iyer ◽  
E. N. Atkinson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Treatment Initiation ◽  
Response Rate ◽  
Multicenter Trial ◽  
Study Entry ◽  
Free Interval ◽  
Grade 3

5589 Background: Systemic therapy for advanced malignant mixed müllerian tumor of the uterus (MMMT) after surgery has been disappointing. Currently, the most common treatment regimen is ifosfamide and platinum. Moderate success has been documented using paclitaxel in MMMT of the ovary. The purpose of this study is to evaluate carboplatin and paclitaxel in patients with advanced (IIIb-IVb) and recurrent MMMT of the uterus. Methods: A single arm, prospective, non-randomized phase II trial opened in October 2001. The planned sample size is 37 evaluable patients, with time to progression and response rate as the primary endpoints. Patients receive carboplatin (AUC 5) and paclitaxel (175 mg/m2) every 21 days. Patients treated adjuvantly receive a total of 6 cycles or until progression or toxicity. Patients with disease present at study entry are treated until progression or toxicity. Results: To date, 18 patients have been enrolled. Seven patients received adjuvant treatment and 11 patients had documented disease at study entry. In the adjuvant group, the median progression-free interval was 15.8 months and median overall survival from treatment initiation was 20.2 months. Four of these 7 patients (57%) continue to be followed with a median follow-up of 19.2 months. In the patients with documented disease, the median progression- free interval was 7.8 months and the median overall survival from treatment initiation was 12.4 months. In this group, there were 3 complete and 4 partial responses (63.6% response rate). Over 45% of patients with disease at study entry are alive with a median follow-up of 14.0 months. Four patients experienced grade 4 granulocytopenia. Only two (11%) had treatment-limiting toxicity, one with grade 3 neuropathy and one with grade 3 fatigue. Conclusions: Carboplatin and paclitaxel appear to have improved tolerability and response rate (63.6%) compared to previous reports of ifosfamide and cisplatin (33% RR) in treating MMMT of the uterus. This regimen seems extremely promising and we are awaiting the final results of this trial. No significant financial relationships to disclose.

scholarly journals Effective use of monoclonal antibodies for treatment of persistent COVID-19 infection in a patient on rituximab

2021 ◽  
Vol 14 (8) ◽  
pp. e243469
Author(s):  
Carlos X Rabascall ◽  
Becky X Lou ◽  
Brianne Navetta-Modrov ◽  
Stella S Hahn
Keyword(s):  
Monoclonal Antibodies ◽  
Symptom Onset ◽  
Severe Disease ◽  
Therapeutic Window ◽  
Immunosuppressed Patient ◽  
Unique Case ◽  
Risk Of Progression ◽  
Immunosuppressed Patients ◽  
Effective Use ◽  
Potential Use

As we are over a year into the COVID-19 pandemic, we have made many forward strides in therapeutics. These treatments, such as monoclonal antibodies, have help mitigate the detrimental and often fatal consequences of COVID-19. The current indication for the use of monoclonal antibodies is mild to moderate COVID-19 infection within 10 days of symptom onset in those who are at high risk of progression to severe disease. However, their role in patients with prolonged symptoms is not clear. We present a unique case of monoclonal antibodies use after 54 days of symptom onset in an immunosuppressed patient with persistent COVID-19 infection despite standard treatment. This case illustrates the potential use of monoclonal antibodies outside of the current recommended therapeutic window in immunosuppressed patients, who may have difficulty with viral clearance.

scholarly journals Prognostic Value of Inflammatory Biomarkers in Patients with Severe COVID-19: A Single-Center Retrospective Study

2021 ◽  
Vol 16 ◽  
pp. 117727192110270
Author(s):  
Gönül Açıksarı ◽  
Mehmet Koçak ◽  
Yasemin Çağ ◽  
Lütfiye Nilsun Altunal ◽  
Adem Atıcı ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Hospital Mortality ◽  
Prognostic Value ◽  
Current Knowledge ◽  
Area Under The Curve ◽  
Prognostic Nutritional Index ◽  
Inflammatory Biomarkers ◽  
Single Center ◽  
Discriminative Ability ◽  
Lymphocyte Ratio

Background: The current knowledge about novel coronavirus-2019 (COVID-19) indicates that the immune system and inflammatory response play a crucial role in the severity and prognosis of the disease. In this study, we aimed to investigate prognostic value of systemic inflammatory biomarkers including C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with severe COVID-19. Methods: This single-center, retrospective study included a total of 223 patients diagnosed with severe COVID-19. Primary outcome measure was mortality during hospitalization. Multivariate logistic regression analyses were performed to identify independent predictors associated with mortality in patients with severe COVID-19. Receiver operating characteristic (ROC) curve was used to determine cut-offs, and area under the curve (AUC) values were used to demonstrate discriminative ability of biomarkers. Results: Compared to survivors of severe COVID-19, non-survivors had higher CAR, NLR, and PLR, and lower LMR and lower PNI ( P < .05 for all). The optimal CAR, PNI, NLR, PLR, and LMR cut-off values for detecting prognosis were 3.4, 40.2, 6. 27, 312, and 1.54 respectively. The AUC values of CAR, PNI, NLR, PLR, and LMR for predicting hospital mortality in patients with severe COVID-19 were 0.81, 0.91, 0.85, 0.63, and 0.65, respectively. In ROC analysis, comparative discriminative ability of CAR, PNI, and NLR for hospital mortality were superior to PLR and LMR. Multivariate analysis revealed that CAR (⩾0.34, P = .004), NLR (⩾6.27, P = .012), and PNI (⩽40.2, P = .009) were independent predictors associated with mortality in severe COVID-19 patients. Conclusions: The CAR, PNI, and NLR are independent predictors of mortality in hospitalized severe COVID-19 patients and are more closely associated with prognosis than PLR or LMR.

Abstract W P172: Prevalence of Positive Dwi Findings in Relation to Tia Etiology

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Yasufumi Gon ◽  
Manabu Sakaguchi ◽  
Syuhei Okazaki ◽  
Hideki Mochizuki ◽  
Kazuo Kitagawa
Keyword(s):  
Symptom Onset ◽  
Clinical Symptoms ◽  
Motor Symptom ◽  
Unknown Etiology ◽  
Symptom Duration ◽  
Motor Symptoms ◽  
Duration Of Symptoms ◽  
Prolonged Duration ◽  
History Of ◽  
Toast Classification

Objective: Previous studies have shown that the prolonged duration of TIA symptoms or ABCD2 score are associated with DWI abnormality, and the presence of DWI abnormality is associated with an increased early risk of stroke. However, there are few reports that show the relation between TIA clinical etiology and DWI abnormality. Our aim of this study is to clarify the prevalence of positive DWI in relation to characteristics of patients and TIA. Methods: The subjects were enrolled from patients who were admitted to our stroke unit within 7 days after symptom onset from January 2006 to July 2013. The diagnosis of TIA was done by NINDS criteria, and we classified TIA etiology by TOAST classification based on clinical symptoms, ECG monitoring, carotid ultrasound, MR angiography and transesophageal echocardiography. All patients underwent DWI-MRI within 7 days after symptom onset. We examined an association between TIA etiology, symptom, duration of symptoms and DWI abnormality. Results: A total of 141 patients (mean 64 years; 63% men) were admitted with TIA during this period. Those included lacuna TIA (n=17, 12.1%), atherothrombotic TIA (n=32, 22.7%), cardioembolic TIA (n=23, 16.3%), TIA due to other causes (n=35, 24.8%), and TIA with unknown etiology (n=34, 24.1%). Prevalence of positive DWI findings were 47.1% in lacunar TIA, 43.7% in atherothrombotic TIA, 52.1% in cardioembloic TIA, 42.8% in TIA due to other causes, and 23.5% in TIA with unknown etiology. DWI abnormality was the most frequent in cardiogenic TIA. In relation to symptom duration, the prevalence of DWI positive findings were 45.2% in less than 1 hour (N=53), 36.6% in 1-3 hour (N=41), 25.0% in 3-6 hour (N=12) and 42.9% in 6-24 hours (N=35). In relation to motor symptoms, there was no difference in prevalence of DWI abnormality between patient with motor symptoms (39.8%, N=113) and without (42.8%, N=28). There was no relation between DWI abnormalities and age, a history of stroke/TIA episode or vascular risk factors. Conclusion: Prevalence of DWI positive findings was high in cardiogenic TIA, and low in TIA with unclassified etiology. There were no relation between DWI abnormality, duration of symptom, and motor symptom.

VERU-111, an oral cytoskeleton disruptor, to treat men with metastatic castration-resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5056-5056
Author(s):  
Mark Christopher Markowski ◽  
Ronald F. Tutrone ◽  
Mario A. Eisenberger ◽  
Christopher Michael Pieczonka ◽  
Robert H. Getzenberg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Androgen Receptor ◽  
Study Entry ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Multidrug Resistance Proteins ◽  
Receptor Targeting ◽  
Phase 1B ◽  
Grade 3 ◽  
Moderate Nausea

5056 Background: VERU-111 is an oral cytoskeletal disruptor that disrupts microtubules supporting the cytoskeleton and has no affinity for multidrug resistance proteins. A phase 1b/2 clinical study has been conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC also resistant to androgen receptor targeting agents. Methods: In the phase 1b component of the study, a 3+3 design with escalating oral dosing of 4.5 mg to 81 mg (7 days on drug/14 days off per 21-day cycle) was utilized. The schedule was also expanded to continuous dosing/cycle. The phase 2 portion utilized 63 mg daily dosing to evaluate efficacy in approximately 40 taxane-naïve men with mCRPC that have failed at least one androgen receptor targeting agent. Results: In the phase 1b portion of the study, 30 taxane-naïve men with mCRPC and a median age of 76 (61-92) were enrolled. 8 had received prior enzalutamide, 12 abiraterone and 10 both. 8 men had bone mets, 5 lymph node, 5 mixed and 1 had soft tissue metastases at study entry. The MTD of VERU-111 is 72mg (3/11 men had grade 3 diarrhea) and the recommended phase 2 dose is 63mg. Grade 3 diarrhea was not observed at doses ≤ 63mg per day and the most common non-dose limiting AEs were mild to moderate nausea, vomiting, diarrhea, and fatigue, with no observed neurotoxicity or neutropenia. Efficacy was assessed by PSA and bone/CT scans. In men treated for ≥ 4 continuous 21-day cycles, 6/10 (60%) had PSA declines, 4(40%) men had ≥ 30% declines and 2(20%) ≥ 50% declines compared to their 21-day cycle baseline PSA. Median PFS is currently 12 months (6-23+ months) with 3 patients continuing on study, 2 of which have been on study for approximately 2 years. In patients receiving at least a single dose of ≥ 63 mg daily (n=19), objective tumor responses were seen in 3 men (16%). The median rPFS in these patients is currently 12.4 months. In the phase 2 portion of the study, 55% of the patients had bone only metastases, 11% had nodal only, 32% had mixed bone and nodal disease and 3% had visceral disease at study entry. 6/32 (19%) were previously treated with abiraterone alone, 12/32 (38%) with enzalutamide alone, and 14/32 (44%) had abiraterone in combination with enzalutamide, proxalutamide or apalutamide. The phase 2 portion of the study is ongoing and objective tumor responses have been observed including a CR and PRs and PSA decreases >50%. Patients have been on study as long as 9 months. Conclusions: This phase 1b/2 clinical trial, demonstrates that oral daily dosing of VERU-111 has a favorable safety profile and that chronic dosing is feasible. The recommended phase 2 dose of 63mg daily has significant durable antitumor activity. These data support a potential prominent role of VERU 111 for the treatment of men with mCRPC who previously failed an androgen receptor targeting agent and prior to the administration of intravenous chemotherapy. Clinical trial information: NCT03752099.

Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study

1999 ◽  
Vol 17 (1) ◽  
pp. 25-25 ◽  
Author(s):  
M. J. Byrne ◽  
J. A. Davidson ◽  
A. W. Musk ◽  
J. Dewar ◽  
G. van Hazel ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Complete Response ◽  
Symptom Improvement ◽  
Median Response ◽  
Grade 3

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.

Paclitaxel, Estramustine Phosphate, and Carboplatin in Patients With Advanced Prostate Cancer

2001 ◽  
Vol 19 (1) ◽  
pp. 44-53 ◽  
Author(s):  
William Kevin Kelly ◽  
Tracy Curley ◽  
Susan Slovin ◽  
Glenn Heller ◽  
John McCaffrey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Complete Response ◽  
Dose Escalation Study ◽  
Time Curve ◽  
Grade 3 ◽  
Safe Dose ◽  
Androgen Independent

PURPOSE: To determine the safety and activity of weekly paclitaxel in combination with estramustine and carboplatin (TEC) in patients with advanced prostate cancer. PATIENTS AND METHODS: In a dose-escalation study, patients with advanced prostate cancer were administered paclitaxel (weekly 1-hour infusions of 60 to 100 mg/m2), oral estramustine (10 mg/kg), and carboplatin (area under the curve, 6 mg/mL-min every 4 weeks). Paclitaxel levels were determined 0, 30, 60, 90, and 120 minutes and 18 hours after infusion, and a concentration-time curve was estimated. Once a safe dose was established, a multi-institutional phase II trial was conducted in patients with progressive androgen-independent disease. RESULTS: Fifty-six patients with progressive androgen-independent disease were treated for a median of four cycles. The dose of paclitaxel was escalated from 60 to 100 mg/m2 without the occurrence of DLT. Posttherapy decreases in serum prostate-specific antigen levels of 50%, 80%, and 90% were seen in 67%, 48%, and 39% (95% confidence interval, 55% to 79%, 35% to 61%, 26% to 52%) of the patients, respectively. Of the 33 patients with measurable disease, two (6%) had a complete response and 13 (39%) had a partial response. The overall median time to progression was 21 weeks, and the median survival time for all patients was 19.9 months. Major grade 3 or 4 adverse effects were thromboembolic disease (in 25% of patients), hyperglycemia (in 38%), and hypophosphatemia (in 42%). Significant leukopenia, thrombocytopenia, and peripheral neuropathy were not observed. CONCLUSION: TEC has significant antitumor activity and is well tolerated in patients with progressive androgen-independent prostate cancer.

scholarly journals Renal Echogenicity as a Predictor of Human Immunodeficiency Virus–Associated Nephropathy: A Cross-Sectional Study at a Tertiary Hospital in Lagos, Southwest Nigeria

2018 ◽  
Vol 34 (4) ◽  
pp. 261-272
Author(s):  
Cletus Uche Eze ◽  
Charles Ugwoke Eze ◽  
Adekunle A. O. Adeyomoye
Keyword(s):  
Human Immunodeficiency Virus ◽  
Serum Creatinine ◽  
Area Under The Curve ◽  
Tertiary Hospital ◽  
Cross Sectional Study ◽  
Cd4 Count ◽  
Cross Sectional ◽  
Immunodeficiency Virus ◽  
Southwest Nigeria ◽  
Grade 3

The objective of this study was to determine the accuracy of sonography in a human immunodeficiency virus–associated nephropathy (HIVAN) diagnosis. A sample of 340 HIVAN patients underwent laboratory CD4+ count, serum creatinine/glomerular filtration rate (GFR) estimation, and sonographic echogenicity grading. The accuracy of sonography in predicting an HIVAN diagnosis was calculated. Mean CD4+ count, serum creatinine, and GFR for male and female HIVAN patients was 153.1 ± 103.2 cells/mm3 and 121.9 ± 91.0 cells/mm3, 218.4 ± 147.4 mmol/L and 222.0 ± 150.4 mmol/L, and 50.1 ± 23.6 mL/min/1.73 m2 and 39.3 ± 20.6 mL/min/1.73 m2, respectively; 56.9% of patients had echogenicity grade 3. On the basis of CD4+ count, serum creatinine, and GFR, the area under the curve was 0.76 and ≈ 1, respectively; the area under the curve was 0.63, 0.79, 0.70, 0.79 and 0.91, 0.99, 1, 1 for grades 0, 1, 2, and 3 echogenicity, respectively. With a high level of apathy to voluntary HIV/AIDS screening and late patient presentation, sonography (grade 3 renal echogenicity) can assist in predicting an HIVAN diagnosis.

Phase I Trial of Docetaxel With Estramustine in Androgen-Independent Prostate Cancer

1999 ◽  
Vol 17 (3) ◽  
pp. 958-958 ◽  
Author(s):  
Daniel P. Petrylak ◽  
Robert B. Macarthur ◽  
John O'Connor ◽  
Gary Shelton ◽  
Timothy Judge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Response Rate ◽  
Area Under The Curve ◽  
Narcotic Analgesics ◽  
Pain Medications ◽  
Psa Response ◽  
Grade 3 ◽  
Recommended Phase Ii Dose ◽  
Androgen Independent

PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a ≥ 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.

A Multi-Centre Prospective Observational Study of Platelet Transfusion Practice in Neonates with Severe Thrombocytopenia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 961-961 ◽  
Author(s):  
Neil Murray ◽  
Sally Ballard ◽  
Angela Casbard ◽  
Mike Murphy ◽  
Irene Roberts ◽  
...  
Keyword(s):  
Observational Study ◽  
Major Bleeding ◽  
Platelet Transfusion ◽  
Transfusion Practice ◽  
Major Haemorrhage ◽  
Study Entry ◽  
Severe Thrombocytopenia ◽  
Minor Bleeding ◽  
Grade 3 ◽  
Platelet Transfusions

Abstract Background: Platelet transfusion practice in neonates is not evidence-based and there is a lack of data relating transfusion to clinical outcome. To inform the design of clinical trials, we conducted a prospective multicentre observational study of platelet transfusion in thombocytopenic neonates to describe: transfusion practice, including reason for transfusion; clinically-related outcomes, including minor and major bleeding and mortality. Methods: Neonates with platelets &lt;60x109/l were studied at 7 UK neonatal intensive care units Mar 05-Jun 06. With parental consent, daily data were collected on minor bleeding (blood staining of oral/nasogastric/endotracheal secretions and stool; microscopic haematuria; petechial rash; oozing from puncture sites - scored 0–7), and major bleeding (intraventricular (IVH), intra-abdominal, pulmonary or renal). Surviving neonates were studied for 7 days or until platelets were ≥60x109/l. Blood counts and all transfusions were directed by the attending neonatologist, with reason for transfusion and its effect on bleeding prospectively documented. Results: 145 of 167 (87%) eligible neonates were enrolled; 123 (85%) were &lt; 37 weeks gestational age (GA), 89 (61%) were male. The study documented 186 episodes of thrombocytopenia (1606 study days) and 309 platelet transfusions given to 91 (63%) neonates. GA, birth weight and age at thrombocytopenic episode were: 27 (24–32) weeks; 825 (675–1370) grams; 5 (2–16) days, respectively [all data median (IQR)]. 21/145 babies (14%) had major IVH (Grade 3/4) at study entry. Platelets (x 109/l) at study entry, and at platelet nadir, and duration of count &lt;60x109/l were: 44 (33–54); 31 (19–42); 2 (1–5) days respectively. In transfused neonates, platelets (x109/l) pre- and post-transfusion, and number of transfusions were: 27 (19–36); 84 (46–138); 2 (1–4) respectively. The principal indications for transfusion were:- platelet count below threshold of unit guideline: 265/309 (86%); deteriorating clinical condition: 17/309 (6%); and significant bleeding: 7/309 (2%). At least 1 episode of minor bleeding was recorded on 622/1606 (39%) of study days. Minor bleeding scores recorded for 12 hours pre- and post each transfusion were [median (IQR)]: 1 (0–2) and 0 (0–1) respectively. New or extension of IVH bleeding to Grade 3/4 occurred in 7 neonates and other major haemorrhage in 9 neonates (4 pulmonary, 3 GI). A total of 20/145 (14%) neonates died, 13 with major IVH bleeding (of which 10 had Grade 3/4 IVH at study entry); all received platelet transfusions [total 87; median 3 (2 to 7). Conclusion: This study confirms that most neonates with severe thrombocytopenia are preterm, most episodes develop after 72 hours of life (median 5 days) and are of short duration (median 2 days). Minor haemorrhage is common and may be reduced by platelet transfusion. Major haemorrhage is uncommon (11%), is associated with mortality (82%) and affected patients receive a large number of platelet transfusions. There is a clear distinction between the majority of thrombocytopenic neonates who receive one or two transfusions as prophylaxis with a good outcome, and the minority who suffer adverse outcomes despite transfusion. Many neonates are transfused with platelets at thresholds below those suggested in guidelines without apparent clinical detriment. These data will be invaluable for planning the randomised trials necessary for rationalising platelet transfusion in these vulnerable patients.

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