Bromocriptine in Parkinson’s Disease: Results Obtained With High and Low Dose Therapy

ABSTRACTThe results obtained with high and low dose bromocriptine therapy were compared in a review assessing the per cent of patients showing improvement (not taking account of the extent of improvement). It is concluded that the response rate with low dose bromocriptine is as good as that obtained with high dose therapy for both de novo and levodopa treated patients. The incidence of adverse effects is similar in the high and low dose treatment groups: More levodopa reduction results in a higher daily bromocriptine requirement. A statistical analysis of 61 bromocriptine-levodopa treated patients showed no positive correlation between bromocriptine dose and severity or duration of Parkinson’s disease.

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Combination Chemotherapy with Cyclophosphamide, Thalidomide and Dexamethasone Achieves a High Response Rate in Patients with Newly Diagnosed, VAD-Refractory and Relapsed Myeloma.

Blood ◽

10.1182/blood.v104.11.1499.1499 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1499-1499 ◽

Cited By ~ 4

Author(s):

Catherine D. Williams ◽

Jennifer L. Byrne ◽

Gamal Sidra ◽

Sonya Zaman ◽

Nigel H. Russell

Keyword(s):

Stem Cell ◽

Vascular Access ◽

Response Rate ◽

De Novo ◽

High Dose ◽

Newly Diagnosed ◽

High Dose Therapy ◽

Dose Therapy ◽

Stem Cell Mobilisation ◽

Relapsed Disease

Abstract The established first-line treatment for younger myeloma patients includes regimens containing high-dose pulsed steroids and a combination of intravenous cytotoxic drugs such as vincristine and adriamycin (e.g.VAD). Response rates of 60% are reported but some patients are refractory. Patients may have complications relating to the need for central vascular access. Oral treatments, such as thalidomide, have shown response rates of about 36% in refractory patients. In an attempt to improve on these results we have evaluated the efficiency and toxicity of a novel oral chemotherapy regimen containing pulsed cyclophosphamide, thalidomide and pulsed dexamethasone (CTD). This regimen consists of a four week cycle of oral cyclophosphamide 500mg, given on days 1, 8 and 15, daily oral thalidomide initiated at a dose of 100mg daily for the first two weeks, increasing to 200mg daily if tolerated, and oral dexamethasone 40mg daily on days 1–4 and 15–18. Patients were treated with 2–6 cycles depending on response. Response criteria were used according to the EBMT/IBMTR guidelines. Results are reported on 62 myeloma patients: 15 with newly diagnosed (de novo) disease, 29 with VAD-refractory myeloma and 17 with relapsed disease. Median age of the patients was 55 years (range 31–73). Isotype was IgG in 38 patients, IgA in 17, light chain in 6 and non-secretory (NS) in 1 patient. Of the 15 patients with de novo disease, a median of 5 courses of CTD were given(range 4–6). All patients responded with 12 achieving a PR and 3 a CR. Of the 29 VAD-refractory patients, 14 had either no response or progressive disease after 2 cycles of VAD and 14 had only a minimal response to VAD with < 50% reduction in paraprotein after 3 cycles. One patient with NS myeloma had <50% reduction in bone marrow plasmacytosis after 3 cycles. PR or CR was achieved in 24 of the 29 patients (83%), with the remaining five achieving < 25% reduction in paraprotein. Twenty nine of the 44 de novo and refractory patients were considered suitable to progress to high dose melphalan and underwent stem cell mobilisation with cyclophosphamide and G-CSF. The median CD34+ cell dose harvested was 5.22 x 106/kg (1.9–11.2). Only one patient failed to mobilise. Twenty eight of these patients have undergone high dose therapy of whom 10 (36%) have achieved a CR. The relapsed disease group included 17 patients of whom 16 had received previous high-dose therapy. The overall response rate (PR/CR) was 71% (12/17). Ten patients went on to receive maintenance thalidomide and 2 a PSCT. Median follow-up is 19 months and 10 of the 17 are still alive. Toxicity of the CTD regimen was minimal with most adverse affects being grade 1 or 2 by the WHO classification. One third of patients suffered constipation and, a quarter, somnolence due to the thalidomide. Dose reduction was rarely required. Peripheral neuropathy was reported by 9% of patients.Grade 3 toxicity was limited to 2 patients who had a DVT and 2 patients who developed febrile neutropenia. Overall, CTD is a highly effective regimen for patients with newly diagnosed myeloma, VAD-refractory disease or relapsed disease. It is well tolerated and does not impair stem cell mobilisation. As it is oral, compliance is good and complications related to vascular access are minimised. This regimen has now gone on to be tested in new patients in a Phase III setting as one arm of the current MRC Myeloma IX trial.

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High-dose therapy with ropinirole in patients with Parkinson's disease

Journal of Neural Transmission ◽

10.1007/s007020100007 ◽

2001 ◽

Vol 108 (11) ◽

pp. 1309-1317 ◽

Cited By ~ 15

Author(s):

M. M�ngersdorf ◽

U. Sommer ◽

M. Sommer ◽

H. Reichmann

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

High Dose ◽

High Dose Therapy ◽

Dose Therapy

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Phase II study of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone (DEX), and lenalidomide (LEN) in patients with newly diagnosed (ND) multiple myeloma (MM)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8518 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8518-8518

Author(s):

R. Baz ◽

M. A. Hussein ◽

D. Sullivan ◽

J. Raychaudhuri ◽

L. Ochoa ◽

...

Keyword(s):

Febrile Neutropenia ◽

Low Dose ◽

Overall Response Rate ◽

Response Rate ◽

High Dose ◽

Hematologic Toxicity ◽

High Dose Therapy ◽

Overall Response ◽

Dose Therapy ◽

Grade 3

8518 Background: We previously reported the results of a phase I/II trial of PLD, low dose DEX and LEN in patients with relapsed and refractory MM in which the MTD of LEN was 10 mg (for 21 of 28 days) and the overall response rate was 75% with 29% of patients achieving nCR or better (Ann Oncol 2006). Accordingly we evaluated this regimen in ND MM. Methods: We hypothesized that patients with ND MM would tolerate this combination better. Accordingly, patients received PLD (40 mg/m2 on day 1), DEX (40 mg on days 1–4) and LEN (25 mg Days 1–21) every 28 days (for 2 cycles beyond best response: 4–8 cycles). Prophylactic low dose aspirin, acyclovir and fluoroquinolone were recommended. Patients not eligible or not wishing to proceed with high dose therapy continued on the tolerated dose of LEN and DEX until disease progression or unacceptable toxicity. Results: Between 2/2008 and 8/2008, 31 of a planned 60 patients were enrolled. 2 patients were screen failures and are not included in subsequent analysis. The mean age was 64 years (41–82) and 58% were males. The median β2microglobulin was 2.8 mg/dL (34% had β2m>3.5). Using the modified SWOG criteria and after a median of 4 cycles of therapy, the overall response rate was 80% with 40% VGPR and better. Two patients had stable disease and 3 patients had progressive disease. Grade 3/4 hematologic toxicity was as follows: neutropenia (48%), anemia (10%), thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity included: Fatigue (21%), infections and febrile neutropenia (20%, only 1 patient with febrile neutropenia), venous thromboembolic events (10%). 14 patients went off study including 8 patients to proceed with high dose therapy. Conclusions: The combination of PLD, LEN and DEX is an active regimen in patients with ND MM. Due to the unexpected higher rates of neutropenia and fatigue, the dose of PLD will be decreased to 30 mg/m2 every 28 days. Updated results will be presented at the time of the meeting. [Table: see text]

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Corrections: levodopa for parkinson’s disease (9 July, page 56)

Drug and Therapeutics Bulletin ◽

10.1136/dtb.28.21.84 ◽

1990 ◽

Vol 28 (21) ◽

pp. 84-84

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Low Dose ◽

Dose Therapy

The table incorrectly described Sinemet LS and Sinemet Plus, which are both capsules, and Madopar 125 and 62.5, which are both tablets. Reference 14 refers to the study by Lees and Stern described in the paragraph ‘Low Dose Therapy’, and should have been cited there, not later.

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Efficacy of NS-718, a Novel Lipid Nanosphere-Encapsulated Amphotericin B, againstCryptococcus neoformans

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.7.1722 ◽

1998 ◽

Vol 42 (7) ◽

pp. 1722-1725 ◽

Cited By ~ 15

Author(s):

Mohammad Ashraf Hossain ◽

Shigefumi Maesaki ◽

Hiroshi Kakeya ◽

Tetsuhiro Noda ◽

Katsunori Yanagihara ◽

...

Keyword(s):

Amphotericin B ◽

Antifungal Agent ◽

Low Dose ◽

Yeast Cells ◽

High Dose ◽

Pulmonary Cryptococcosis ◽

High Dose Therapy ◽

Dose Therapy

ABSTRACT In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC forCryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

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Low-dose versus high-dose therapy for Gaucher disease: goals and markers

Blood ◽

10.1182/blood-2006-07-033233 ◽

2007 ◽

Vol 109 (1) ◽

pp. 387-387 ◽

Cited By ~ 5

Author(s):

Carla E. M. Hollak ◽

Maaike de Fost ◽

Johannes M. F. G. Aerts ◽

Stephan vom Dahl

Keyword(s):

Gaucher Disease ◽

Low Dose ◽

High Dose ◽

High Dose Therapy ◽

Dose Therapy

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Autotransplants for Multiple Myeloma (MM) – An Update of the Arkansas Experience Since 1989 In Almost 4000 Patients with Special Emphasis on Third and Further Transplants.

Blood ◽

10.1182/blood.v116.21.1352.1352 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1352-1352

Author(s):

Bijay Nair ◽

Elias J. Anaissie ◽

Sarah Waheed ◽

Yazan Alsayed ◽

Rachael Sexton ◽

...

Keyword(s):

Conflicts Of Interest ◽

Outcome Data ◽

Hematopoietic Progenitor Cell ◽

High Dose ◽

Front Line ◽

High Dose Therapy ◽

Free Survival ◽

Treatment Groups ◽

Dose Therapy ◽

Previously Treated

Abstract Abstract 1352 Background: The Arkansas program has emphasized high hematopoietic progenitor cell (HPC) yields since its inception in 1989, in order to enable further high-dose therapy for relapse, rescue patients from hematopoietic compromise due to extensive cumulative genotoxic or novel agent dosing, and provide a fall-back option in the case MDS develops. Here we are examining the overall outcome data among 3888 patients undergoing HPC-supported therapy since 1989. Patients and Methods: Patients were grouped according to whether they received front-line Total Therapy (TT) protocols (TT-P, n=1452), non-TT protocols for previously treated MM (non-TT-P, n= 1155) or non-protocol therapies (non-P, n=1281). Overall survival (OS) and event free survival (EFS) were measured from the 1st high-dose therapy (Tx-1) intervention and examined in the context of baseline variables present prior to Tx-1, the aforementioned 3 treatment groups, and intervals between successive Tx interventions. Results: OS/EFS from Tx-1 was longest with TT-P (5-yr estimates, 67%/52%) followed by non-TT-P (5-yr estimates, 43%/30%) and non-P (5-yr estimates, 36%/27%) (p<0.0001, p<0.0001). Among all 3888 patients, 2773 (71%) received Tx-2 including 2385 (86%) within 6 months of Tx-1; 405 (10%) received Tx-3 including 140 (35%) within 2yr of Tx-2; 58 (1.5%) received Tx-4 including 44 (76%) within 2yr form Tx-3; 12 (0.3%) received Tx-5 all within 2yr from Tx-4; and 3 patients had Tx-6. When examined in the context of the 3 different treatment groups, 1157/1231 (94%) of the TT-P group had Tx-2 within 6mo, 51/169 (30%) had Tx-3 within 2yr of Tx-2, 51/169 (30%) had Tx-4 within 2yr of Tx-3, and 7/7 (100%) had a Tx-5 within 2 yr of Tx-4. Among 1155 non-TT-P patients, 646/822 (79%) had Tx-2 within 6mo of Tx-1, 37/129 (29%) had Tx-3 within 2yr of Tx-2, 14/18 (78%) had Tx-4 within 3yr of Tx-3, and all 4 (100%) receiving Tx-5 had done so within 2yr of Tx-4. Among 1281 non-P patients, 582/720 (81%) had received Tx-2 within 6mo of Tx-1, 52/107 (49%) had received Tx-3 within 2yr of Tx-2, 7/10 (70%) had received Tx-4 within 2yr of Tx-3, and 1 patient received Tx-5 within 2yr of Tx-4. KM plots from Tx-3 were similar among the 3 treatment groups with median OS of 16mo for TT-P, 14mo for non-TT-P and 11mo for non-P (p=0.13); median EFS were 7, 8, and 6 months (P=0.17). Timely application within 6mo resulted in superior OS and EFS from Tx-2 (OS: 79 v 23 months, EFS: 48 v 14 months; both P<0.0001). Multivariate Cox analyses examining post-Tx EFS and OS revealed TT-P superiority from Tx-1 and Tx-2 over non-TT-P and non-P; Tx-2 within 6mo of Tx-1 provided superior post-Tx-2 EFS and OS; while benefit from Tx-3 was not apparent until at least 2yr had elapsed since Tx-2. CA within 1 year of Tx-1 adversely affected EFS and OS from Tx-1, Tx-2 and Tx-3. Other adverse baseline parameters included low albumin for EFS and OS post-Tx-1; and B2M >=3.5mg/L for EFS and OS post-Tx-1 and post-Tx-2. Conclusions: We confirm that front-line TT-P provides superior clinical outcomes in comparison with back-up/salvage non-TT-P and non-P Tx, emphasizing the benefit from planned upfront protocol therapy. Timely application of Tx-2 within 6 months of Tx-1 extended both EFS and OS from Tx-2, validating our concept of maximum tumor cyto-reduction and avoiding MM re-growth. Tx-3 was useful when applied beyond 2yr from Tx-2, in support of the notion that longer disease control prior to relapse favorably impacts subsequent salvage Tx. Disclosures: No relevant conflicts of interest to declare.

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Comparison of Blood Graft Cellular Content in Myeloma (MM) Patients and Non-Hodgkin Lymphoma (NHL) Patients Mobilized with Chemotherapy Plus G-CSF with or without Plerixafor

Blood ◽

10.1182/blood.v120.21.4414.4414 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4414-4414

Author(s):

Esa Jantunen ◽

Ville Varmavuo ◽

Raija Silvennoinen ◽

Piia Valonen ◽

Taru Kuittinen ◽

...

Keyword(s):

B Lymphocytes ◽

Low Dose ◽

Lymphoid Cells ◽

High Dose ◽

Cellular Composition ◽

High Dose Therapy ◽

Dose Therapy ◽

Non Hodgkin Lymphoma ◽

Previous Therapy ◽

Cd34 Cells

Abstract Abstract 4414 Background: Cellular composition of blood graft collected to support high-dose therapy may have important implications in regard to hematopoietic and immune reconstitution after high-dose therapy. Mobilization method used may have effect on graft composition as well as previous therapy given to the patients. Methods: We have retrospective analyzed by flow cytometry cellular composition of freezed blood grafts in 34 patients with NHL (chemotherapy + G-CSF mobilization 15, add-on plerixafor 19 patients) and compared the observations with those of 17 MM patients mobilized either with low-dose cyclophosphamide + G-CSF (n=12) or with add-on plerixafor (n=5). The analyses were performed from the first graft collected from the chemomobilized patients or from the first draft collected after the plerixafor injection, respectively. Antibodies used included CD34, CD38, CD133 in regard to CD34+ subclasses and CD3, CD4, CD8, CD19 and CD3CD16/CD56 to analyze lymphocyte subsets. In addition, 7-aminoactinomycin D staining was used to assess the amount of nonviable CD34+ and lymphoid cells. Results: In regard to the patients mobilized without plerixafor, MM patients had higher content of CD34+ cells (4.9 vs. 2.0 × 106/kg, p=0.009) as well as lower proportion of more primitive stem cells (0.8 vs. 1.9 % of all CD34+ cells, p=0.075) when compared to NHL patients. The amount of B-lymphocytes was also significantly higher in MM patients (0.5 × 106/kg vs. 0.0, p< 0.001). No differences were observed in the total amount of T (CD3+) cells, NK cells or in the proportion of nonviable CD34+ or lymphoid cells. Of the plerixafor treated patients, the amount of B-lymphocytes was higher in MM patients (1.8 × 106/kg vs. 0.0, p<0.001) as well as CD4/CD8 ratio (2.56 vs. 1.0, p=0.004) when compared to NHL patients. Conclusion: As there appears to be differences between MM and NHL patients mobilized with or without plerixafor, it might be advisable to analyze separately effects of mobilization therapy to graft content and post-transplant outcomes in these diseases. Apparently the type and intensity of previous therapy given to the patients (e.g. rituximab) has important effects on graft cellular composition. Disclosures: Jantunen: Genzyme: Has participated in EU Leadership meeting organized by Genzyme as well as Medical Advisory Board meeting organized by Genzyme Other, Honoraria. Silvennoinen:Genzyme: Consultancy.

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