Optimal combination therapy with tropisetron in 445 patients with incomplete control of chemotherapy-induced nausea and vomiting.

1994 ◽  
Vol 12 (11) ◽  
pp. 2439-2446 ◽  
Author(s):  
F Hulstaert ◽  
S Van Belle ◽  
H Bleiberg ◽  
J L Canon ◽  
M Dewitte ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Moderate Increase ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Antiemetic Agent ◽  
To Receive

PURPOSE This study evaluated tropisetron (Navoban; Sandoz Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent. PATIENTS AND METHODS One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [i.v.] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo. RESULTS Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate. CONCLUSION The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.

Rituximab in Combination With Fludarabine Chemotherapy in Low-Grade or Follicular Lymphoma

2005 ◽  
Vol 23 (4) ◽  
pp. 694-704 ◽  
Author(s):  
M.S. Czuczman ◽  
A. Koryzna ◽  
A. Mohr ◽  
C. Stewart ◽  
K. Donohue ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Infectious Complications ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Similar Response ◽  
Open Label ◽  
Treatment Naïve

Purpose To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naïve or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. Patients and Methods This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. Results An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naïve and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. Conclusion Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Complete Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Grade 3 ◽  
To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

Recombinant human interferon- for condylomata acuminata: a randomized, double-blind, placebo-controlled study of intralesional therapy

1997 ◽  
Vol 8 (10) ◽  
pp. 614-621 ◽  
Author(s):  
Jacob Bornstein ◽  
Bruno Pascal ◽  
Doron Zarfati ◽  
Nimrod Goldschmid ◽  
Haim Abramovici
Keyword(s):  
Response Rate ◽  
Complete Response Rate ◽  
Condylomata Acuminata ◽  
Complete Response ◽  
Response To Treatment ◽  
Controlled Study ◽  
Human Interferon ◽  
Double Blind ◽  
Hpv Dna ◽  
Genital Condylomata

To assess the efficacy of a novel glycosylated mammalian cell derived recombinant human interferon- (r-hIFN--1a) in the intralesional treatment of genital condylomata acuminata. The study was randomized, double-blind and placebo-controlled. Patients ( n =60) with up to 8 distinct condylomata acuminata were randomized to receive either one million international units (IU) of r-hIFN--1a or placebo intralesionally into each lesion, 3 times a week, for a total of 9 occasions. Biopsies were taken from each patient before enrolment to allow human papillomavirus (HPV) testing, and patients were tested for the development of anti-IFN- antibodies. Efficacy was assessed by measuring the complete response rate 3 months after treatment. The complete response rate was not significantly better with r-hIFN--1a than with placebo. However, after 3 months, 73.3% of patients treated with r-hIFN--1a had experienced at least a partial response to treatment, compared with 33.3% of placebo-treated patients. At 19 days and 6 weeks, r-hIFN--1a produced a significantly larger reduction in the area of condylomata. Lesions with detectable HPV 6 or 11 showed a trend towards a better response rate to treatment with rhIFN--1a than lesions where no HPV DNA was detected. The treatment was well tolerated. In the 5 patients who developed non-neutralizing anti-IFN- antibodies, therapeutic efficacy was not compromised. Intralesional r-hIFN--1a was effective in the reduction of the size of genital condylomata acuminata.

Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer

2017 ◽  
Vol 35 (34) ◽  
pp. 3859-3866 ◽  
Author(s):  
Nobuyuki Katakami ◽  
Toshiyuki Harada ◽  
Toru Murata ◽  
Katsunori Shinozaki ◽  
Masakazu Tsutsumi ◽  
...  
Keyword(s):  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Spontaneous Bowel Movement ◽  
Patients With Cancer ◽  
End Point ◽  
Μ Opioid Receptor ◽  
To Receive

Purpose Opioid-induced constipation (OIC) is a frequent and debilitating adverse effect (AE) of opioids—common analgesics for cancer pain. We investigated the efficacy and safety of a peripherally acting μ-opioid receptor antagonist, naldemedine (S-297995), for OIC, specifically in patients with cancer. Patients and Methods This phase III trial consisted of a 2-week, randomized, double-blind, placebo-controlled study (COMPOSE-4) and an open-label, 12-week extension study (COMPOSE-5). In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned on a 1:1 basis to receive once-daily oral naldemedine 0.2 mg or placebo. The primary end point was the proportion of spontaneous bowel movement (SBM) responders (≥ 3 SBMs/week and an increase of ≥ 1 SBM/week from baseline). The primary end point of COMPOSE-5 was safety. Results In COMPOSE-4, 193 eligible patients were randomly assigned to naldemedine (n = 97) or placebo (n = 96). The proportion of SBM responders in COMPOSE-4 was significantly greater with naldemedine than with placebo (71.1% [69 of 97 patients] v 34.4% [33 of 96 patients]; P < .0001). A greater change from baseline was observed with naldemedine than with placebo in the frequency of SBMs/week (5.16 v 1.54; P < .0001), SBMs with complete bowel evacuation/week (2.76 v 0.71; P < .0001), and SBMs without straining/week (3.85 v 1.17; P = .0005). In COMPOSE-4, more patients treated with naldemedine than with placebo reported treatment-emergent AEs (TEAEs) (44.3% [43 of 97 patients] v 26.0% [25 of 96 patients]; P = .01); in COMPOSE-5, 105 (80.2%) of 131 of patients reported TEAEs. Diarrhea was the most frequently reported TEAE in COMPOSE-4 (19.6% [19 of 97 patients] v 7.3% [seven of 96 patients] with naldemedine v placebo) and COMPOSE-5 (18.3% [24 of 131 patients] with naldemedine). Naldemedine was not associated with signs or symptoms of opioid withdrawal and had no notable impact on opioid-mediated analgesia. Conclusion Once-daily oral naldemedine 0.2 mg effectively treated OIC and was generally well tolerated in patients with OIC and cancer.

scholarly journals A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: A phase II double-blind, randomized placebo-controlled study

2012 ◽  
Vol 35 (1) ◽  
pp. 1 ◽  
Author(s):  
Hong-Wen Chen ◽  
I-Hsin Lin ◽  
Yu-Jen Chen ◽  
Kao-Hwa Chang ◽  
Meng-Hao Wu ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Treatment Cycle ◽  
Response Rate ◽  
Controlled Study ◽  
Advanced Cancer Patients ◽  
Open Label ◽  
Double Blind ◽  
Cancer Related Fatigue ◽  
To Receive ◽  
Blind Manner

Purpose: This study investigated the efficacy of the botanical-derived drug, PG2, a partially purified extract of Astragalus membranaceus, as a complementary and palliative medicine for managing cancer-related fatigue (CRF). Methods: Patients with advanced cancer and moderate to severe CRF were randomized to receive either PG2 or a placebo (normal saline, NS) in the first treatment cycle (four weeks) in a double-blind manner; thereafter, on the next cycle (four weeks), all patients received open-label treatment with PG2. Results: PG2 significantly improved CRF in the NS-primed group. In the first four week cycle, PG2 administration resulted in a greater fatigue-improvement response rate than seen with NS alone. In addition, approximately 82% of patients who reported an improvement of fatigue symptoms following the first cycle of PG2 experienced sustained benefits after administration of the second treatment cycle. Among patients treated with PG2 who did not report an improvement in symptoms throughout the first treatment cycle, approximately 71% showed significant improvement after the second treatment cycle. No major or irreversible toxicities were observed with PG2 treatment. Conclusion: PG2 might be an effective and safe treatment for relieving CRF among advanced cancer patients.

Fc-Gamma Receptor Polymorphisms Are Associated with Susceptibility to and Recovery from Pediatric Immune Thrombocytopenia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 867-867 ◽  
Author(s):  
Katja M.J. Heitink-Polle ◽  
Annemieke G. Laarhoven ◽  
Marrie C.A. Bruin ◽  
Barbera Veldhuisen ◽  
Sietse Q. Nagelkerke ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Ivig Treatment ◽  
Newly Diagnosed ◽  
Fc Gamma Receptor ◽  
Patient Counselling ◽  
Gamma Receptor ◽  
To Receive

Abstract Introduction: Immune thrombocytopenia (ITP) in children is a rare autoimmune disorder characterized by isolated thrombocytopenia. Platelet specific autoantibodies are often present leading to accelerated clearance of opsonized platelets by Fc-gamma receptor (FcγR) bearing phagocytes, particularly in the spleen. Both activating FcγRs as well as the inhibitory FcγRIIb are subject to genetic variation that affects their function. This includes mutations resulting in loss of expression; for example only the FCGR2C*ORF with an open reading frame leads to FcγRIIc expression. On myeloid and natural killer cells, FcγRIIc expression enhances IgG-mediated activation. Similarly, functional FcγRIIb polymorphisms also exist (FCGR2B*232I/T), with the FCGR2B*232T variant being functionally impaired in downregulating activating FcγRs and the B-cell receptor. We evaluated whether FcγR polymorphisms are associated with occurrence of ITP, response to intravenous immunoglobulin (IVIg) therapy and recovery in children with newly diagnosed ITP. Patients and methods: Children aged 3 months-16 years with newly diagnosed ITP, a platelet count below 20x109/L and with mild to moderate bleeding were included in the randomized multicenter TIKI trial (Therapy with or without IVIg for Kids with acute ITP; NTR study ID TC1563). Patients were randomized to receive either a single dose of IVIg (0.8 g/kg) or to receive careful observation and medical treatment only in case of severe bleeding. At diagnosis, blood samples were taken to perform the multiplex ligation-dependent probe amplification (MLPA) assay, assessing copy number variations and detecting all known FcγR polymorphisms. Results: From May 2009 until May 2015, 180 newly diagnosed patients were enrolled in this part of our study. ITP patients showed an FcγR profile different from that of healthy controls, with an overrepresentation of FCGR2C*ORF (31.7% versus 19.6%, p=0.007) and its associated promoter 2B.2, a higher allele frequency of FCGR3A*158V (41.4% versus 32.8%; p=0.019), and less often FCGR3B-HNA1a (9.4% versus 18.1%, p=0.032). In the observation group (n=81), all children with complete recovery at 1 week (n=17) were homozygous for 232I in FCGR2B (p=0.016). In patients randomized to receive IVIg, complete response rate after one week was 68.4%; complete responders were either homozygous FCGR2B*232I or heterozygous FCGR2B*232I/232T. No complete responses to IVIg were seen in the three patients with the homozygous FCGR2B*232T genotype (p=0.03). In patients with a homozygous FCGR2B*232I genotype combined with the 2B.4 promoter haplotype, complete response rate was significantly higher than in patients lacking this combination (93.3% versus 64.6%, respectively; p=0.03). Conclusion: Functional FcγR polymorphisms in FCGR2C, FCGR3A and FCGR3B genes are associated with newly diagnosed ITP in children. Furthermore, the less functional 232T-FcγRIIb isoform is associated with the lack of early recovery, either with or without IVIg treatment. FcγR profiles can be regarded as a risk factor to develop ITP during childhood. FcγR profiles are associated with the clinical course and response to IVIg treatment suggesting that determination of the FcγR profile can be of additional value in patient counselling and decision algorithms whether or not to start IVIg treatment in ITP. Disclosures No relevant conflicts of interest to declare.

scholarly journals Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Gerd Horneff ◽  
Tatyana Dvoryakovskaya ◽  
Rina Denisova ◽  
Irina Nikishina ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Controlled Trial ◽  
Randomized Study ◽  
Primary Objective ◽  
Disease State ◽  
Inactive Disease ◽  
Open Label ◽  
Standard Regimen ◽  
Double Blind ◽  
Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

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