Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 546-554 ◽  
Author(s):  
KM Sullivan ◽  
RP Witherspoon ◽  
R Storb ◽  
P Weiden ◽  
N Flournoy ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Aseptic Necrosis ◽  
Actuarial Survival ◽  
Double Blind ◽  
Host Disease ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Recurrent Malignancy ◽  
Blind Comparison

We conducted a randomized, double-blind comparison of prednisone and placebo (group I) v prednisone and azathioprine (1.5 mg/kg/day) (group II) as early treatment of extensive chronic graft-v-host disease (GVHD). Patients with platelet counts less than 100,000/microL were placed into therapy with prednisone alone (group III). All three groups received identical doses of prednisone (1 mg/kg every other day) and one double-strength trimethoprim-sulfamethoxazole (TMP-SMX) tablet twice daily. Between January 1980 and December 1983, 179 previously untreated patients were enrolled and 164 were evaluable. Patients randomized to group I (n = 63) and group II (n = 63) were well matched for prognostic factors; those placed into group III (n = 38) had more frequent acute GVHD and progressive onset of chronic GVHD. Median duration of therapy was 2 years. Complications included diabetes (5%), aseptic necrosis (5%) and infection. For groups I, II, and III, the respective incidence of infection was disseminated varicella, 11%, 24%, 34%; bacteremia, 6%, 11%, 34%; and interstitial pneumonia, 5%, 14%, 18%. Recurrent malignancy was the most frequent cause of death and did not differ significantly across the groups. Nonrelapse mortality, however, did differ: 21% in group I, 40% in group II, and 58% in group III (I v II, P = .003; I v III, P = .001). Forty patients in group I, 30 in group II, and 10 in group III survive with a minimum follow-up of 3.8 years. Karnofsky performance scores for 68 survivors are 90% to 100%, scores for seven survivors are 70% to 89% and scores for five survivors are less than 70%. Actuarial survival at 5 years after transplant is 61% in group I, 47% in group II, and 26% in group III (I v II, P = .03; I v III, P = .0001). Treatment with prednisone alone results in fewer infections and better survival than prednisone and azathioprine in standard-risk chronic GVHD. Treatment with prednisone alone is less effective in high-risk patients with thrombocytopenia, and other strategies are required.

scholarly journals Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 546-554 ◽  
Author(s):  
KM Sullivan ◽  
RP Witherspoon ◽  
R Storb ◽  
P Weiden ◽  
N Flournoy ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Aseptic Necrosis ◽  
Actuarial Survival ◽  
Double Blind ◽  
Host Disease ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Recurrent Malignancy ◽  
Blind Comparison

Abstract We conducted a randomized, double-blind comparison of prednisone and placebo (group I) v prednisone and azathioprine (1.5 mg/kg/day) (group II) as early treatment of extensive chronic graft-v-host disease (GVHD). Patients with platelet counts less than 100,000/microL were placed into therapy with prednisone alone (group III). All three groups received identical doses of prednisone (1 mg/kg every other day) and one double-strength trimethoprim-sulfamethoxazole (TMP-SMX) tablet twice daily. Between January 1980 and December 1983, 179 previously untreated patients were enrolled and 164 were evaluable. Patients randomized to group I (n = 63) and group II (n = 63) were well matched for prognostic factors; those placed into group III (n = 38) had more frequent acute GVHD and progressive onset of chronic GVHD. Median duration of therapy was 2 years. Complications included diabetes (5%), aseptic necrosis (5%) and infection. For groups I, II, and III, the respective incidence of infection was disseminated varicella, 11%, 24%, 34%; bacteremia, 6%, 11%, 34%; and interstitial pneumonia, 5%, 14%, 18%. Recurrent malignancy was the most frequent cause of death and did not differ significantly across the groups. Nonrelapse mortality, however, did differ: 21% in group I, 40% in group II, and 58% in group III (I v II, P = .003; I v III, P = .001). Forty patients in group I, 30 in group II, and 10 in group III survive with a minimum follow-up of 3.8 years. Karnofsky performance scores for 68 survivors are 90% to 100%, scores for seven survivors are 70% to 89% and scores for five survivors are less than 70%. Actuarial survival at 5 years after transplant is 61% in group I, 47% in group II, and 26% in group III (I v II, P = .03; I v III, P = .0001). Treatment with prednisone alone results in fewer infections and better survival than prednisone and azathioprine in standard-risk chronic GVHD. Treatment with prednisone alone is less effective in high-risk patients with thrombocytopenia, and other strategies are required.

scholarly journals Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 555-561 ◽  
Author(s):  
KM Sullivan ◽  
RP Witherspoon ◽  
R Storb ◽  
HJ Deeg ◽  
S Dahlberg ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Gvhd ◽  
Renal Dialysis ◽  
Marrow Transplant ◽  
Primary Treatment ◽  
Aseptic Necrosis ◽  
Actuarial Survival ◽  
Host Disease ◽  
Group I ◽  
Group Ii

Abstract Therapy of chronic graft-v-host disease (GVHD) has been unsatisfactory in patients with platelet counts less than 100,000/microL. Survival at 5 years after marrow transplant is only 26% in such patients treated with trimethoprim-sulfamethoxazole (TMP-SMX) and every other day with prednisone. Since October 1982, 61 patients with high-risk extensive chronic GVHD were treated with a new alternating-day regimen of prednisone (1 mg/kg every other day) and oral cyclosporine (6 mg/kg every 12 hours every other day) with one double-strength TMP-SMX tablet twice daily. Forty patients (group I) received primary treatment of thrombocytopenic chronic GVHD (median platelet count 35 [range 7 to 87] x 10(3)/microL). Twenty-one patients (group II) received salvage treatment after failing initial prednisone +/- azathioprine. Twenty-one patients in group I and 15 in group II survive with a minimum of 2 years and a median of 3.7 years follow-up. At 4 years after transplant, actuarial survival is 51% (group I) and 67% (group II). Causes of death included interstitial pneumonia (six), relapse (five), GVHD without infection (five), infection (four), organ failure (three), and hemorrhage (two). Mortality increased with the progressive type onset of chronic GVHD and treatment failure. Toxicity included hypertension (13), nephrotoxicity (nine), nausea (seven), aseptic necrosis (five), neurologic abnormalities (four), and diabetes (three). Median cyclosporine levels at four and 36 hours were 296 and 64 ng/mL, respectively. Four patients required permanent discontinuation of cyclosporine, but none required renal dialysis. Karnofsky performance scores for 25 survivors are 90% to 100%, scores for six survivors are 70% to 89%, and scores for five survivors are less than 70%. Alternating-day cyclosporine and prednisone has acceptable toxicity and appears to improve survival in patients with high-risk chronic GVHD.

scholarly journals Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 555-561
Author(s):  
KM Sullivan ◽  
RP Witherspoon ◽  
R Storb ◽  
HJ Deeg ◽  
S Dahlberg ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Gvhd ◽  
Renal Dialysis ◽  
Marrow Transplant ◽  
Primary Treatment ◽  
Aseptic Necrosis ◽  
Actuarial Survival ◽  
Host Disease ◽  
Group I ◽  
Group Ii

Therapy of chronic graft-v-host disease (GVHD) has been unsatisfactory in patients with platelet counts less than 100,000/microL. Survival at 5 years after marrow transplant is only 26% in such patients treated with trimethoprim-sulfamethoxazole (TMP-SMX) and every other day with prednisone. Since October 1982, 61 patients with high-risk extensive chronic GVHD were treated with a new alternating-day regimen of prednisone (1 mg/kg every other day) and oral cyclosporine (6 mg/kg every 12 hours every other day) with one double-strength TMP-SMX tablet twice daily. Forty patients (group I) received primary treatment of thrombocytopenic chronic GVHD (median platelet count 35 [range 7 to 87] x 10(3)/microL). Twenty-one patients (group II) received salvage treatment after failing initial prednisone +/- azathioprine. Twenty-one patients in group I and 15 in group II survive with a minimum of 2 years and a median of 3.7 years follow-up. At 4 years after transplant, actuarial survival is 51% (group I) and 67% (group II). Causes of death included interstitial pneumonia (six), relapse (five), GVHD without infection (five), infection (four), organ failure (three), and hemorrhage (two). Mortality increased with the progressive type onset of chronic GVHD and treatment failure. Toxicity included hypertension (13), nephrotoxicity (nine), nausea (seven), aseptic necrosis (five), neurologic abnormalities (four), and diabetes (three). Median cyclosporine levels at four and 36 hours were 296 and 64 ng/mL, respectively. Four patients required permanent discontinuation of cyclosporine, but none required renal dialysis. Karnofsky performance scores for 25 survivors are 90% to 100%, scores for six survivors are 70% to 89%, and scores for five survivors are less than 70%. Alternating-day cyclosporine and prednisone has acceptable toxicity and appears to improve survival in patients with high-risk chronic GVHD.

Platelet Function Studies in Normal Volunteers and Patients with Angina Pectoris

1979 ◽  
Author(s):  
J.J.C. Jonker ◽  
den G.J.H. Ottolander
Keyword(s):  
Platelet Aggregation ◽  
Angina Pectoris ◽  
Platelet Function ◽  
Normal Range ◽  
Double Blind ◽  
Group Iii ◽  
Platelet Survival ◽  
Group I ◽  
Group Ii

In 30 normal subjects (group I) and in 89 patients with angina pectoris we studied: the platelet survival time (PST), the platelet aggregation test I (PAT I) acc. to Breddin, the platelet aggregation ratio (PAR) acc. to Wu and Hoak and the Filtragometer log TA acc. to Hornstra. The patients were divided in two groups: 46 patients had already been treated for 6 months with Clofibrate (group II) and 43 patients with placebo (group III) in a double blind trial. The average PST (T½) was within the normal range (group I 99 hrs. group II 105,7 hrs.; group III 102,0 hrs.). About 20% of patients of group II and III had abnormally shortened T½. The PAT I was on average abnormal in group II and III (PAT I in group II 2,3; group III 2,7), but group II normalized after 12 months treatment (PAT I 1,85). The PAR was abnormal in group III, while group II was within the normal range (group I 0,87; group II 0,82; group III 0,69). The log TA results were abnormal in group II and III (group I 2, 45, group II 2,1; group III 2, 1), after 12 months treatment the patient group remained abnormal (group II 2,2; group III 2,1). We failed to find a correlation between the four platelet function tests, nor with these tests and basic laboratory values. The PAT I, the PAR and the Filtragometer seems to be valuable in the detection of abnormal platelet behavior in vitro, but it does not mean than an abnormal platelet survival in vivo occurs in the same individuals.

scholarly journals Comparing the effects of dezocine with lidocaine on prevention of propofol injection pain in adults: a prospective randomized double-blind trial

2019 ◽  
Author(s):  
Xuqin Zhu ◽  
Songlin Jia ◽  
Yajun Xu ◽  
Zhirong Sun
Keyword(s):  
Lower Incidence ◽  
Elective Surgery ◽  
Group Iv ◽  
Patient Comfort ◽  
Injection Pain ◽  
Double Blind ◽  
Group V ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Abstract Background Propofol injection pain (PIP) is common and may decrease patient comfort. The aim of this study was to compare the effects of dezocine with lidocaine on prevention of PIP. Methods 235 patients, who scheduled for elective surgery, aged 18-80 years and ASA (American Society of Anesthesiologists) I or II, were randomly assigned into five groups (n = 47 each). All patients were induced through the dor­sal hand vein or antecubital vein. The five groups were given the following medication intravenously: saline (Group I), lidocaine 20 mg (Group II), lidocaine 40 mg (Group III), dezocine 2 mg (Group IV) and dezocine 4 mg (Group V). Twenty seconds later all patients received a propofol infusion and were asked to grade pain or discomfort in the hand or forearm according to a four-point scale until anesthesia. Results Three groups showed a significantly lower incidence of total PIP than Group I: Group III (OR (Odds ratio): 0.39 (0.16, 0.93)); Group IV (OR: 0.21 (0.09, 0.51)) and Group V (OR: 0.12 (0.05, 0.30)). Group IV showed a significantly lower incidence of total PIP than Group II (OR: 0.32 (0.13, 0.77)). Group V showed a significantly lower incidence of total PIP than Group II (OR: 0.15 (0.06, 0.39)) or Group III (OR: 0.30 (0.13, 0.72)). Conclusion Dezocine is a novel agent to alleviate PIP and appears to be more effective than lidocaine.

scholarly journals Comparing the effects of dezocine with lidocaine on prevention of propofol injection pain in adults: a prospective randomized double-blind trial

2019 ◽  
Author(s):  
Xuqin Zhu ◽  
Songlin Jia ◽  
Yajun Xu ◽  
Zhirong Sun
Keyword(s):  
Lower Incidence ◽  
Elective Surgery ◽  
Group Iv ◽  
Patient Comfort ◽  
Injection Pain ◽  
Double Blind ◽  
Group V ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Abstract Background Propofol injection pain (PIP) is common and may decrease patient comfort. The aim of this study was to compare the effects of dezocine with lidocaine on prevention of PIP.Methods 235 patients, who scheduled for elective surgery, aged 18–80 years and American Society of Anesthesiologists (ASA) I or II, were randomly assigned into five groups (n = 47 each). All patients were induced through the dor­sal hand vein or antecubital vein. The five groups were given the following medication intravenously: saline (Group I), lidocaine 20 mg (Group II), lidocaine 40 mg (Group III), dezocine 2 mg (Group IV) and dezocine 4 mg (Group V). Twenty seconds later all patients received a propofol infusion and were asked to grade pain or discomfort in the hand or forearm according to a four-point scale until anesthesia.Results Three groups showed a significantly lower incidence of total PIP than Group I: Group III (OR [Odds ratio]: 0.39 (0.16, 0.93)); Group IV (OR: 0.21 (0.09, 0.51)) and Group V (OR: 0.12 (0.05, 0.30)). Group IV showed a significantly lower incidence of total PIP than Group II (OR: 0.32 (0.13, 0.77)). Group V showed a significantly lower incidence of total PIP than Group II (OR: 0.15 (0.06, 0.39)) or Group III (OR: 0.30 (0.13, 0.72)).Conclusion Dezocine is a novel agent to alleviate PIP and appears to some extent to be more effective than lidocaine.

Incidence of Late Failure Following Myeloablative Conditioning with BuCy2 and Matched Sibling Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2172-2172
Author(s):  
Shubham Pant ◽  
Sayed Mehdi Hamadani ◽  
Pamela Crilley ◽  
Jeffrey Szer ◽  
Anthony J. Dodds ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Acute Myeloid

Abstract Allogeneic stem cell transplantation (ASCT) is an important curative modality for patients with acute myeloid leukemia (AML), but no large studies with mature followup after a uniform conditioning regimen and stem cell source have been reported. We previously published (Copelan EA. Blood; 78:838–43, 1992) the results of 127 patients with AML who underwent ASCT following preparation with oral busulfan (16 mg/kg) and cyclophosphamide (120mg/kg) (BuCy2) with a median follow-up of 3 years. We now present data on 316 AML patients, including the initial cohort, who underwent ASCT from 1984 to 1995 at 7 participating institutions the United States and Australia. All patients received bone marrow grafts from HLA-identical sibling donors following myeloablative preparation with BuCy2. One hundred fifty-seven patients were transplanted in first remission (CR1, group I), 49 in second remission (CR2, group II) and 110 patients were beyond CR2 or had refractory disease (group III). Cyclosporine or tacrolimus-based regimens were routinely administered to prevent graft-versus-host-disease (GVHD). Median follow-up of surviving patients exceeds 12 years (range 3 – 18 years). At the time of analysis 126 patients (40%) were alive. The estimated leukemia-free survival (LFS) for group I at 3 and 12 years is 63% (95% CI: 47 – 79%) and 49% (95% CI: 33 – 66%), for group II is 50% (95% CI 36 – 64%) and 33% (95% CI: 17 – 49%) and group III is 25% (95% CI: 17 – 32%) and 16% (95%CI: 8 – 24%) respectively. The estimated relapse rate for patients in group I at 3 and 12 years is 15% (95%CI: 9 – 21%) and 28% (95% CI: 20 – 36%), for group II is 38% (95% CI: 24 – 52%) and 48% (95% CI: 31 – 65%), and group III is 56% (95% CI: 4 – 68%) and 65% (95% CI: 53 – 77%). For the entire cohort (n=317), using multivariate analysis, younger age (p<0.004) and transplantation in CR1 (p<0.001) were predictive of long-term overall survival (OS) and LFS. Transplantation in CR1 (p<0.001), and presence of chronic GVHD (p=0.003) were associated with decreased risk of relapse. One hundred forty-two patients were alive and free of leukemia at 3 years; of these patients, 75% are leukemia-free survivors at 12 years. Considering only these patients, the cumulative incidence of relapse beyond 3 years was 17% and the cumulative incidence of non-relapse mortality was 9%; only 2 patients died beyond 3 years from respiratory failure. For this group, none of the factors analyzed (including age, remission status at the time of transplantation or the presence of chronic GVHD) was predictive for OS, LFS or relapse. In conclusion, although most remissions in AML patients surviving leukemia-free for at least 3 years following ASCT are durable, late relapse occurs in 17%. One in four patients alive and free of leukemia at 3 years will relapse or die from NRM over the subsequent 9 years. Figure Figure

Dysfunction Patterns of Epoxy-Treated Tissue Heart Valves

Kardiologiia ◽  
2019 ◽  
Vol 59 (10) ◽  
Author(s):  
T. V. Glushkova ◽  
E. A. Ovcharenko ◽  
N. V. Rogulina ◽  
K. Yu. Klyshnikov ◽  
Yu. A. Kudryavtseva ◽  
...  
Keyword(s):  
Heart Valves ◽  
Adhesion Formation ◽  
Actuarial Survival ◽  
Group Iii ◽  
Tissue Valve ◽  
Group I ◽  
Group Ii ◽  
Group 2 ◽  
Calcific Deposits ◽  
Tissue Heart Valves

Purpose: to perform comparative morphological analysis of causes of dysfunction of epoxy-treated, xenoaortic and xenopericardial, tissues heart valves.Materials and methods. We included in this study 475 patients with mitral valve disease who have undergone heart valve replacement with tissue valve: (“KemCor”, n=211 [group 1]; “PeriCor”, n=126 [group 2]; and “UniLine”, n=138 [group 3]). Degenerative changes in 26 tissue valves (n=9 “KemCor”, n=11 “PeriCor”, and n=6 “UniLine”) explanted from the mitral position during the repeat replacement were evaluated macroscopically for the presence of calcifications, perforations, leaflet tears and ruptures, pannus, and leaflet fusion to the stent frame. Analysis of survival, freedom from dysfunction and reoperation of the studied tissue heart valves was performed for the period from January 1, 1995 to March 01, 2017.Results: Pannus overgrowth on the stent struts with extension onto the leaflets was seen on 53.8% of explanted tissue valves. “KemCor” and “PeriCor” tissue valves demonstrated over 70% rate of adhesion formation at the commissure, and in 93% of these cases there were leaflet ruptures at the commissure. Signs of calcification of different grades had 57.6% of specimens. Over 50% of “PeriCor” and “UniLine” tissue valve specimens had calcification at the stent frame. Calcified pannus was noted in 35% of all studied tissue heart valves. Interestingly, dysfunction in 53.3% of the studied tissue heart valves with detected calcification was not associated with calcific deposits. The 6-year actuarial survival for groups I, II and III was 73.5, 66.1 and 87.6%, respectively (group I vs. group II, p=0.6; group II vs. group III - p<0.05; group I vs. group III - p<0.05). The actuarial freedom from reoperation was 81.9%, 75.0% and 94.2%, respectively (pI-II>0.05; pII-III<0.05; pI-III<0.05). The actuarial freedom from dysfunction was 79.6%, 75.0%, and 94.2%, respectively (pI-II>0.05; pII-III<0.05; pI-III<0.05).Conclusion. The structure of dysfunctions of the studied tissue heart valves was represented by primary tissue failure, calcification and pannus growth. Specific design of the “UniLine” valve allowed to prevent the formation of adhesions between leaflets and the frame in the commissure buttress area, and as a result leaflet rupture from the stent struts. Xenopericardial “UniLine” tissue valves turned out to be superior to xenoaortic “KemCor” and “PeriCor” tissue valves in terms of survival, freedom from reoperations and dysfunction within the 6-year follow-up.

Long-Term Follow-Up of Treatment for Acute Myeloid Leukemia with Allogeneic Hematopoetic Cell Transplantation Using BuCy2 as Preparation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3370-3370
Author(s):  
Shubham Pant ◽  
Pamela Ann Crilley ◽  
Anthony J. Dodds ◽  
Jeffrey Szer ◽  
Brian J. Bolwell ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Group Iii ◽  
Late Failure ◽  
Group I ◽  
First Remission ◽  
Group Ii ◽  
Acute Myeloid

Abstract In 1991, we reported the results of 127 patients with Acute Myeloid Leukemia (AML) who underwent conditioning for allogeneic transplant with busulfan, 4 mg/kg on each of 4 days and cyclophosphamide 60 mg/kg on each of 2 days. In the current abstract, we report data on 295 patients, including the initial cohort, who underwent allogenic transplantation for AML from 1984 to 1995 at 7 participating institutions. Median age of patients is 33. One hundred forty nine men and 126 women underwent transplant. All patients received marrow from related HLA-identical donors. One hundred seven patients (36%) remain alive. One hundred forty one patients were transplanted in first remission (group I), 43 in second remission (group II) and 111 patients were in > 2nd remission or had refractory disease (group III). The median follow-up of patients in the initial study was 3 years and is 12 years in the current study. Seventy-five percent of patients surviving 3 years after transplantation are estimated survivors 12 years after transplant. Relapse (20), chronic GVHD (5) and infection (3) were the major causes of death in patients who died more than 3 years after transplantation. The estimated relapse rate for group I at 3 and 12 years is 18%(95% CI: 2–32%) and 29% (95% CI 11–47%) for group II is 40% (95% CI: 8–72%) and 52% (95% CI: 16–84%), and group III is 59% (95% CI: 37–81%) and 69% (95% CI: 45–93%) respectively. The estimated leukemia-free survival (LFS) for group I at 3 and 12 years is 60% (95% CI: 44–76%) and 47% (95% CI: 29–65%), for group II is 47% (95% CI: 17–77%) and 34% (95% CI: 4– 64%)and group III is 22% (95% CI: 6–38%) and 15% (95% CI: 1–29%) respectively. Remission stage was predictive of long-term LFS (P<0.001), with patients transplanted in first remission doing better than the rest. Older age was a risk factor for late failure (death or relapse beyond 3 years, P=0.05). Remission stage at transplant (p=0.44), chronic GVHD (P=0.08) and acute GVHD (P=0.12) were not significantly predictive of late failure. In conclusion a vast majority of patients alive and well at 3 years post transplant seem destined to be cured. A proportion of patients do fail beyond 3 years, but the remission stage of disease at transplant is not predictive of late failure.

Prevention of Cisplatin-Induced Emesis by the Oral Neurokinin-1 Antagonist, MK-869, in Combination With Granisetron and Dexamethasone or With Dexamethasone Alone

2001 ◽  
Vol 19 (6) ◽  
pp. 1759-1767 ◽  
Author(s):  
Daniel Campos ◽  
Jose Rodrigues Pereira ◽  
Rick R. Reinhardt ◽  
Carlos Carracedo ◽  
Sergio Poli ◽  
...  
Keyword(s):  
High Dose ◽  
Delayed Emesis ◽  
Double Blind ◽  
Acute Emesis ◽  
Group Iii ◽  
Group I ◽  
Efficacy Parameter ◽  
Group Ii ◽  
Neurokinin 1 ◽  
Present Trial

PURPOSE: The NK1-receptor antagonist MK-869 (L-754,030) has demonstrated antiemetic activity in humans receiving chemotherapy. Objectives of the present trial included the first assessment of oral MK-869 plus dexamethasone compared with a 5HT3 antagonist plus dexamethasone for prevention of acute and delayed emesis after high-dose cisplatin. Furthermore, the study sought to confirm that addition of MK-869 to a 5HT3 antagonist plus dexamethasone was more effective than just the 5HT3 antagonist plus dexamethasone for prevention of acute and delayed emesis. METHODS: This multicenter, double-blind, parallel-group trial in 351 cisplatin-naïve patients evaluated prevention of acute (0 to 24 hours) and delayed emesis (primary efficacy parameter; days 2 to 5) after cisplatin (≥70 mg/m2). Patients were randomized to four groups (I to IV) (n = number randomized; number evaluable): granisetron (10 μg/kg intravenously) pre-cisplatin followed by placebo on days 2 to 5 (group I) (n = 90; 90); granisetron and MK-869 (400 mg PO [by mouth]) pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group II) (n = 86; 84); MK-869 (400 mg PO) the evening before and pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group III) (n = 89; 88); or MK-869 (400 mg PO) pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group IV) (n = 86; 84). All patients also received dexamethasone (20 mg PO) before cisplatin. Additional medication was available to treat emesis or nausea at any time. RESULTS: In the acute period, 57%, 80%, 46%, and 43% of patients were without emesis in groups I, II, III, and IV, respectively (P < .01 for group II v group I). In the delayed period, the proportion of patients without emesis in groups I, II, III, and IV was 29%, 63%, 51%, and 57%, respectively (P < .01 for groups II, III, and IV v group I). The distribution of nausea scores in the delayed period was lower when comparing group II with group I (P < .05 for days 1 to 5 and days 2 to 5). One serious adverse event (dizziness) was rated as possibly related to MK-869. CONCLUSION: Once daily oral administration of MK-869 was effective in reducing delayed emesis and nausea after high-dose cisplatin. However, the combination of the 5HT3 antagonist plus dexamethasone was numerically superior to MK-869 plus dexamethasone in reducing acute emesis. Confirming and extending previous findings, the triple combination of a 5HT3 antagonist, MK-869, and dexamethasone provided the best control of acute emesis.

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