Phase II study of caphosol oral rinse for prevention of oral mucositis (OM) in sarcoma patients (pts) receiving multicycle doxorubicin-based chemotherapy (CT): Randomized study with cross-over to palifermin for severe OM.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19520-e19520
Author(s):  
Saroj Vadhan-Raj ◽  
Dejka M. Araujo ◽  
Jonathan C. Trent ◽  
Xiao Zhou ◽  
Joseph A. Ludwig ◽  
...  
Keyword(s):  
Keratinocyte Growth Factor ◽  
Randomized Study ◽  
Study Drug ◽  
Weighted Kappa ◽  
Secondary Prophylaxis ◽  
High Dose ◽  
Serious Adverse Event ◽  
Oral Rinse ◽  
Experienced Grade ◽  
Severe Mucositis

e19520 Background: Mucositis is a common complication in cancer pts receiving CT. We have shown that palifermin (recombinant Keratinocyte Growth Factor), administered as single dose prior to CT, alleviated severe mucositis in pts receiving doxorubicin-based CT (Ann Int Med 2010). Caphosol is a supersaturated electrolyte solution of calcium phosphate that has been indicated as oral rinse for xerostomia and as an adjunct to treat OM induced by radiation or high-dose CT. Purpose of the study was to evaluate the preliminary efficacy of Caphosol in pts receiving CT. Methods: Pts were randomized 1:1 to Caphosol vs. baking soda (control) as an oral rinse five times daily from initiation of CT. All pts received doxorubicin (75 or 90 mg/m2 by continuous infusion over 3 days) with ifosfamide (10 gm/m2) or cisplatin (120 mg/m2). Pts that experienced Grade (Gr) > 3 mucositis received palifermin (180 mcg/kg) iv 3 days before CT in subsequent cycles. Results: 28 of 30 pts received treatment and were evaluble; 15 men and 13 women, with median age 51 (range, 20-65 yrs). Incidence of Gr > 2 OM was 57% (8 of 14 pts) for Caphosol vs. 86% (12 of 14) for control (P=0.21). Incidence of Gr > 3 OM was 29% (4/14) for Caphosol vs. 43% (6/14) for control (P=0.43). However, the benefit was limited to oral but not other GI mucosal sites. Of 10 pts (Caphosol: 4, BS: 6,) with Gr > 3 OM, 6 crossed over to palifermin (Caphosol: 3, BS: 3); the other 4 pts (Caphosol: 1, BS: 3) came off the study. All 6 pts, that received palifermin, avoided severe OM in the next cycle. The median duration of Gr > 2 OM in the cycle before cross-over was 8 days (range: 5-12) vs. 0 days (0-3) in palifermin cycle (p=0.0032) and Gr > 3 OM was 5 days (2-7) vs. 0 days (p=0.0015). Oral assessment and the pts-reported outcome were in substantial agreement for the OM grading (weighted kappa, 0.78, 95% CI: 0.44-0.87, p<0.0001). No serious adverse event related to the study drug was observed. Conclusions: There was a trend for less severe OM with Caphosol vs. control. Secondary prophylaxis with palifermin alleviated severe mucositis in all pts who previously experienced severe mucositis during multi-cycle CT.

Safety Trial with the 5Ht1B/1D Agonist Avitriptan (BMS-180048) in Patients with Migraine who have Experienced Pressure, Tightness, and/or pain in the Chest, Neck, and/or throat following Sumatriptan

Cephalalgia ◽  
1998 ◽  
Vol 18 (8) ◽  
pp. 546-551 ◽  
Author(s):  
CGH Dahlöf ◽  
L Falk ◽  
M Risenfors ◽  
CP Lewis
Keyword(s):  
Adverse Event ◽  
Migraine Attack ◽  
Myocardial Function ◽  
Vital Signs ◽  
Study Drug ◽  
Holter Monitoring ◽  
High Dose ◽  
Serious Adverse Event ◽  
Clinically Significant ◽  
Electrocardiogram Ecg

We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography. Migraine sufferers who in two-thirds of all attacks treated with sumatriptan had experienced chest/throat/neck symptoms were chosen for study. Baseline measures included vital signs, a 12-lead ECG and an echocardiogram. Patients ( n=51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack. If pressure, tightness, and/or pain in the chest, neck, and/or throat occurred, an ECG was obtained, and a repeat echocardiogram was done while the symptoms were present in order to monitor for impairment of myocardial function. If symptoms of these types did not occur within 60 min after administration of the study drug, a second echocardiogram was obtained. Forty-five patients (88%) reported at least one adverse event and 23 (45%) experienced pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of avitriptan. No clinically significant myocardial abnormalities were observed in any patient, even in those who had experienced the targeted symptoms. No other serious adverse event occurred. We concluded that the typical 5HT1B/1D agonist-induced chest/throat/neck symptoms are most unlikely to be of cardiovascular origin.

Analysis of the Clinical Impact of the Use of Palifermin in Patients Undergoing Autologous Peripheral Blood Progenitor Cell Transplantation for Multiple Myeloma and Relapsed Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4332-4332
Author(s):  
Kari Kolm ◽  
Ronan Foley ◽  
Jolanta Jeziorowska ◽  
Deborah C Marcellus ◽  
Ann Benger ◽  
...  
Keyword(s):  
Keratinocyte Growth Factor ◽  
Clinical Status ◽  
Underlying Disease ◽  
Entire Group ◽  
High Dose ◽  
Heparin Binding ◽  
Number Of Patients ◽  
Conditioning Regimens ◽  
Relapsed Lymphoma ◽  
Severe Mucositis

Abstract Severe mucositis remains a serious complication of autologous PBPC transplantation. Keratinocyte growth factor/KGF (Palifermin) is a 28kd heparin-binding glycoprotein that specifically binds the KGF receptor resulting in a range of biological events including increased mucosal epithelial thickness. Administration of palifermin to patients undergoing TBI-based autologous PBPC transplantation has been shown to reduce the incidence and duration of severe mucositis. In the current study we retrospectively evaluated the use of palifermin in patients with myeloma and relapsed lymphoma undergoing non-TBI autologous PBPC transplantation with high-dose melphalan and BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimens respectively. Palifermin was given at a dose of 60 mcg/kg/day on days −5 to −3 in patients with myeloma, days −10 to −8 in patients with lymphoma, and days 0 to +2 in all patients. Depending on clinical status and distance from our centre, patients had the opportunity of early discharge on day +1 with outpatient follow-up. G-CSF was administered (5 mcg/kg/day) starting on day +5 in all patients. Of a total of 81 patients, 32 patients received palifermin (23 myeloma, 9 lymphoma) and were compared to a concurrent non-palifermin treated population of 49 patients (27 myeloma, 22 lymphoma). Patients were comparable with respect to age (overall mean 54.5 years), except that patients with myeloma receiving palifermin were slightly older (mean 60 vs. 55 y, p=0.04), and the numbers of infused CD34 positive cells per kg were similar. There were 46 male and 35 female patients. Administration of palifermin was safe and generally well tolerated with 97% of patients receiving all scheduled doses; rash was seen in 32% of cases. The use of palifermin did not influence engraftment of leukocytes or platelets in either myeloma or lymphoma patients. Analysis of length of stay (LOS) following reinfusion in the entire group suggested a difference of 2 days favouring the palifermin group (mean 11.8 vs 13.8 days), but this was not statistically significantly different. There were also no statistically detectable differences in LOS in palifermin treated or untreated patients with myeloma (mean 13.5 vs 10.5 days) or lymphoma (mean 7.7 vs 17.9 days) respectively, although the number of patients with lymphoma receiving palifermin was small. Patients with myeloma appeared to have higher rates of significant mucositis compared with lymphoma (74% vs 48%, p=0.03) but this was not significant in an exploratory logistic regression analysis when age, gender, underlying disease, administration of palifermin and infused number of PBPC were included in the analysis. We conclude that palifermin can be safely administered to patients undergoing non-TBI high dose therapy and autologous PBPC transplantation. Although there was a suggestion of some improvements in LOS with palifermin, the small numbers of patients limit the strength of such conclusions. Further prospective studies in non-TBI conditioning regimens will help to further define the potential benefits of palifermin in reducing mucositis and its consequences.

scholarly journals High-dose Aprotinin in Cardiac Surgery—A Prospective, Randomized Study

1994 ◽  
Vol 22 (5) ◽  
pp. 529-533 ◽  
Author(s):  
M. J. Swart ◽  
P. C. Gordon ◽  
P. B. Hayse-Gregson ◽  
R. A. Dyer ◽  
A. L. Swanepoel ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Placebo Group ◽  
Blood Loss ◽  
Artery Bypass ◽  
Randomized Study ◽  
Postoperative Blood Loss ◽  
High Dose ◽  
Maintenance Infusion ◽  
Transfusion Requirements ◽  
High Dose Aprotinin

Fifty patients undergoing primary coronary artery bypass surgery and 50 patients undergoing valve surgery received either high-dose aprotinin (2 million units loading dose, 2 million units added to the CPB prime, and 500,000 units/hr maintenance infusion) or placebo. Mean postoperative blood loss in the first six hours was reduced from 321 ml in the placebo group to 172 ml in the aprotinin group (95% confidence interval (CI) for difference = 95 to 189 ml). Seven patients in the placebo group and 16 patients in the aprotinin group did not require transfusion with homologous blood. This study adds to the growing body of evidence that the administration of high-dose aprotinin reduces blood loss and blood transfusion requirements associated with primary cardiac surgery.

scholarly journals Monotherapy with Intravenous Followed by Oral High-Dose Ciprofloxacin versus Combination Therapy with Ceftazidime plus Amikacin as Initial Empiric Therapy for Granulocytopenic Patients with Fever

2000 ◽  
Vol 44 (12) ◽  
pp. 3264-3271 ◽  
Author(s):  
Helen Giamarellou ◽  
Harry P. Bassaris ◽  
George Petrikkos ◽  
Wilhelm Busch ◽  
Michel Voulgarelis ◽  
...  
Keyword(s):  
Randomized Study ◽  
Empirical Therapy ◽  
Unknown Origin ◽  
Empiric Therapy ◽  
Oral Route ◽  
Severe Neutropenia ◽  
Combination Group ◽  
High Dose ◽  
Standard Regimen ◽  
Oral Ciprofloxacin

ABSTRACT The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm3) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intravenously at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; δ = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm3). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.

scholarly journals Standard-dose versus high-dose radiotherapy with concurrent chemotherapy in esophageal cancer: A prospective randomized study

2018 ◽  
Vol 07 (01) ◽  
pp. 27-30 ◽  
Author(s):  
Navin Nayan ◽  
M. Bhattacharyya ◽  
Vikas K. Jagtap ◽  
A. K. Kalita ◽  
R. Sunku ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Total Dose ◽  
Standard Dose ◽  
Randomized Study ◽  
Complete Response ◽  
Concurrent Chemotherapy ◽  
Prospective Randomized Study ◽  
High Dose ◽  
Large Sample Size

Abstract Objective: The objective of this study is comparision of local and distant control rates with high-dose versus standard-dose radiotherapy along with concurrent chemotherapy in esophageal cancer – a prospective randomized study. Materials and Methods: Histologically proven Stage I–III patients with carcinoma esophagus were randomized into two groups. One group has been treated with standard-dose radiotherapy, i.e., a total dose of 50.4 Gy (1.8 Gy/day, 28#, 5 days/week). The other group (study arm) has received high-dose radiotherapy, i.e. a total dose of 64.8 Gy (1.8 Gy/day, 36#, 5 days/week). Both groups have received 2 cycles of 3 weekly concurrent chemotherapy (cisplatin 75 mg/m[2] on day 1 and 5-fluorouracil 750 mg/m[2] continuous intravenous infusion over 24 h on day 1–4). Follow-up response evaluation was done by both endoscopy and computed tomography scan after 6–8 weeks and after 2 months thereafter. Results: Out of a total of 28 patients, 68% showed a complete response, 14% showed partial response, and 18% patients developed progressive disease at first and subsequent follow up (median follow-up of 21 months). Among the complete response patients, rates were higher in high-dose group compared to standard-dose radiotherapy group (71% vs. 64%, P = 0.38). Treatment-related toxicities were acceptable in both groups. Conclusion: High-dose radiotherapy with concurrent chemotherapy seems to be more effective with acceptable toxicity in our study. However, further follow-up and large sample size may be required to validate the current study conclusion.

Reduction of the Minimum Alveolar Concentration of Isoflurane by Dexmedetomidine 

1997 ◽  
Vol 86 (5) ◽  
pp. 1055-1060 ◽  
Author(s):  
Riku Aantaa ◽  
Marja-Leena Jaakola ◽  
Antero Kallio ◽  
Jussi Kanto
Keyword(s):  
Minimum Alveolar Concentration ◽  
Study Drug ◽  
Abdominal Hysterectomy ◽  
Skin Incision ◽  
Control Group ◽  
High Dose ◽  
Anesthesia Induction ◽  
Drug Infusion ◽  
Target Plasma Concentration ◽  
End Tidal

Background alpha 2-Adrenergic agonists have been shown to reduce anesthetic requirements of other anesthetics, and they may even act as complete anesthetics by themselves at high doses in animal models. The present study was designed to define the interaction of intravenous infusion of dexmedetomidine, an alpha 2-adrenergic agonist, and isoflurane in patients having surgery by using the minimum alveolar concentration (MAC) of isoflurane as the measure of anesthetic potency. Methods Forty-nine women scheduled for abdominal hysterectomy were randomly allocated to receive either a placebo infusion (n = 16) or a two-stage infusion of dexmedetomidine with target plasma concentration of 0.3 ng/ml (n = 17) or 0.6 ng/ml (n = 16). The study drug infusion was commenced 15 min before induction of anesthesia with thiopental and alfentanil and was continued until skin incision. The end-tidal concentration of isoflurane for each patient was predetermined according to the "up-down" method of Dixon, and it was maintained for at least 15 min before the patient's response to skin incision was assessed. Results The MAC of isoflurane was 0.85% end-tidal in the control group, 0.55% end-tidal with the low dose of dexmedetomidine, and 0.45% end-tidal with the high dose of dexmedetomidine. Conclusions The MAC of isoflurane in the control group was lower than that reported previously in similar patients having surgery, probably due to anesthesia induction with thiopental and alfentanil. Nevertheless, with the high dose of dexmedetomidine, the MAC of isoflurane was still 47% less than that without dexmedetomidine.

High-dose estradiol improves cognition for women with AD: Results of a randomized study

Neurology ◽  
2001 ◽  
Vol 57 (4) ◽  
pp. 605-612 ◽  
Author(s):  
S. Asthana ◽  
L. D. Baker ◽  
S. Craft ◽  
F. Z. Stanczyk ◽  
R. C. Veith ◽  
...  
Keyword(s):  
Randomized Study ◽  
High Dose
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