scholarly journals SUN-190 Metastatic Adrenocortical Carcinoma in Remission After a Single Dose of Gemcitabine

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Muriel Tania L Go ◽  
Tiffany K Hor ◽  
Paolo K Soriano
Keyword(s):  
Single Dose ◽  
Adrenocortical Carcinoma ◽  
Salvage Therapy ◽  
Vena Cava ◽  
Pulmonary Nodules ◽  
Predictive Biomarkers ◽  
Complete Response ◽  
High Dose ◽  
Second Line ◽  
One Year

Abstract Background Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of one per million population per year. Overall prognosis is poor especially in the presence of distant metastasis where five-year survival rate is 10%. Aside from chemotherapy along with mitotane, second-line regimens are not well-established, and therapeutic options remain limited. Here we present a case of metastatic ACC with rapid and complete remission after salvage therapy with gemcitabine (GEM). Clinical Case A 28-year-old man presented with night sweats, 10-lb weight loss and abdominal pain for three months. An abdominal CT showed a 13x14 cm complex mass partially effacing the inferior vena cava (IVC) and a chest CT showed multiple pulmonary micronodules. Biochemical evaluation was unremarkable, confirming a non-functioning adrenal tumor. The patient underwent right adrenalectomy, hepatectomy, right diaphragm resection and cavotomy of IVC. Pathology confirmed ACC with extra-adrenal and vascular invasion. He then underwent adjuvant intensity-modulated radiation therapy with no evidence of disease on imaging thereafter. However, he was lost to follow-up for six months and returned with new enlarging pulmonary nodules. He was started on chemotherapy (cisplatin, etoposide, adriamycin) with mitotane which were discontinued after two months, due to intractable vomiting despite high dose glucocorticoids and anti-emetics. He was then enrolled in a clinical trial using immunotherapy with nivolumab and ipilimumab which led to a significant decrease in the size of pulmonary metastases. His clinical course was complicated by the development of type 1 diabetes mellitus and proliferative glomerulonephritis related to immunotherapy. After one year of immunotherapy, repeat imaging showed disease progression with new pulmonary nodules. These agents were discontinued, and he was then given a single dose of GEM. Subsequent imaging with CT chest, abdomen and pelvis three months later showed complete response with resolution of lung nodules. He has no evidence of disease one year post therapy and continues to undergo active surveillance. Discussion GEM-based chemotherapy has shown to be a modestly active regimen based on a multicenter study which demonstrated a partial response or stable disease in 4.9% and 25% of cases, respectively, with a median duration of 26 weeks. Median progression-free survival is 12 weeks (range 1 to 94). From the available data, GEM remains an important option for salvage therapy however, to date, there are no reliable predictive biomarkers to potentially identify responsive patients. Conclusion This is an extremely rare case of metastatic ACC achieving complete response after definitive surgery and a single dose of gemcitabine, despite failing first-line chemotherapy and immunotherapy. The unusual positive response may lead to the consideration of its use as a second line regimen.

Lenalidomide Maintenance Significantly Improves Progression-Free Survival (PFS) in Patients with Chemosensitive Relapse of Diffuse Large B-Cell Lymphoma (DLBCL) Who Are Not Eligible for Autologous Stem Cell Transplantation (ASCT) or Experienced Relapse after Transplantation: Results of a Multicentre Phase II Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1547-1547
Author(s):  
Andrés J.M. Ferreri ◽  
Marianna Sassone ◽  
Marianna Chiozzotto ◽  
Michele Spina ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Salvage Therapy ◽  
Null Hypothesis ◽  
De Novo ◽  
Phase Ii Trial ◽  
Haematological Toxicity ◽  
Complete Response ◽  
High Dose ◽  
Intestinal Infarction ◽  
One Year

Abstract BACKGROUND: Patients (pts) with relapsed DLBCL who cannot be treated with consolidative ASCT or allogeneic transplantation exhibit a poor prognosis, with a 1-year PFS of 30-40%. Despite a high response rate to salvage therapy, these pts invariably experience early relapse and die of lymphoma. Single-drug maintenance may be a good alternative to intensified consolidation to prolong response duration in these high-risk pts. Lenalidomide is an oral immunomodulatory agent, active against DLBCL, which can be taken for years with an excellent safety profile. Accordingly, we designed a multicenter phase II trial addressing safety and efficacy of lenalidomide maintenance in pts with chemosensitive relapse of DLBCL not eligible for consolidative ASCT or experiencing relapse after ASCT (NCT00799513). Herein, we report the primary endpoint analysis. METHODS: Selection criteria were: 1) adult HIV-negative pts; 2) histologically-proven de novo or transformed DLBCL; 3) relapsed disease responsive (partial or complete response) to conventional-dose rituximab-containing salvage therapy; 4) ECOG PS ≤3; 5) time to progression (TTP) from the previous line ≥3 months. After confirmation of objective response to salvage therapy, pts were registered and treated with lenalidomide 25 mg/day once daily for 21 days out of 28, for two years or until lymphoma failure or unacceptable toxicity. Primary endpoint was the 1-yr PFS. Simon's two-stage optimal design was used. The null hypothesis that the true 1-yr PFS is 30% was tested against a one-sided alternative. The trial design yields a type I error rate of 5% and power of 80% when the true 1-year PFS is 50%. To demonstrate this PFS improvement, 47 pts were needed. The null hypothesis would be rejected if 19 or more pts progression-free at one year were observed. RESULTS: 41 pts were enrolled (median age 72, range 34-86; M:F ratio: 1.5). Thirty pts had a de novo DLBCL, 11 had a transformed DLBCL; 29 pts were enrolled after the first relapse, 12 after the 2nd - 4th relapse. All pts were previously treated with anthracycline- and rituximab-based combination, plus ASCT in 6 pts. The median TTP after the previous line was 17 months (range 3-121). Most pts had unfavourable features: IPI ≥2 in 34 (83%) pts, advanced disease in 33 (80%), extranodal disease in 29 (71%), high LDH in 18 (44%). Twelve pts had HCV and/or HBV infection. Salvage combination included high-dose-cytarabine in 23 pts, high-dose-ifosfamide in 6, anthracycline in 6 and bendamustine in 6. Response to salvage therapy was complete in 25 pts and partial in 16. Twenty-three pts received the planned maintenance; lenalidomide was interrupted due to lymphoma relapse in 8 pts, toxicity in 5 (diarrhoea in 2, rash, prolonged neutropenia, intestinal infarction), and patient's refusal in 5 (diarrhoea in 4, rash). Dose reduction to 10 or 15 mg/d, mostly due to rash or neutropenia, was indicated in 17 pts. Toxicity was mild; there were 6 SAEs (febrile neutropenia in 4, diarrhoea, intestinal infarction) in 5 pts. Grade 4 haematological toxicity consisted of neutropenia in 17 pts and thrombocytopenia in 2. Grade 3-4 non-haematological toxicity consisted of diarrhoea in 3 pts and rash in 5. HBV/HCV seropositivity was not associated with higher toxicity. Six of the 16 pts in partial response after salvage therapy achieved a complete remission during lenalidomide maintenance. At a median follow-up of 16 months, 29 pts remained relapse free, with a 1-year PFS of 75±8%. Importantly, 21 pts were progression-free at one year, with the early achievement of the primary endpoint. Thirty-two pts are alive (NED in 25), 8 pts died of lymphoma and one of intestinal infarction, with a 1-yr OS of 84±7%. Age ≤70 years, normal LDH level, and complete response at registration were independently associated with better PFS and OS, whereas gender, DLBCL category, HBV/HCV infection, and TTP after previous line (< vs. ≥12 months) were not. Assessment of prognostic effect of ontogenic stratification by NanoString is ongoing. CONCLUSIONS: With the early achievement of the primary endpoint, this is the first prospective trial showing a positive effect of maintenance in pts with relapsed DLBCL. Lenalidomide maintenance is feasible and well tolerated in this elderly population, but diarrhoea and rash remain frequent dose-limiting side effects. The evident improvement in survival figures warrants further investigation of immunomodulators maintenance in these high-risk pts. Disclosures Ferreri: celgene: Consultancy, Research Funding. Rusconi:Roche: Honoraria.

scholarly journals Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis

2019 ◽  
Vol 25 (7) ◽  
pp. 1169-1186 ◽  
Author(s):  
Matthew C Choy ◽  
Dean Seah ◽  
David M Faleck ◽  
Shailja C Shah ◽  
Che-Yung Chao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ulcerative Colitis ◽  
Single Dose ◽  
Salvage Therapy ◽  
Meta Analysis ◽  
Optimal Dose ◽  
High Dose ◽  
Free Survival ◽  
Severe Ulcerative Colitis ◽  
The Impact

AbstractBackgroundInfliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis.MethodsStudies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported.ResultsForty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels.ConclusionsIn acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.

Comparison of standard versus high dose of paclitaxel with ifosfamide and cisplatin (TIP) in salvage therapy of germ cell tumors (GCTs).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15028-e15028
Author(s):  
Jozef Mardiak ◽  
Michal Mego ◽  
Viera Miskovska ◽  
Zuzana Sycova-Mila ◽  
Jana Obertova ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Complete Response ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Primary Tumor Site ◽  
Prognostic Features ◽  
First Relapse

e15028 Background: Currently, TIP with higher dose of paclitaxel (250mg/m2) is considered standard salvage chemotherapy in GCTs with good prognostic features. However, until 2007, we utilized regimen with standard dose of paclitaxel (175mg/m2). The aim of this study was to compare the efficacy of TIP with the standard versus higher dose of paclitaxel as first salvage therapy for patients with relapsed GCTs. Methods: This retrospective study included 64 patients with relapsed GCTs treated with TIP as first salvage therapy between 1998 and 2010 in two major cancer centers in Slovakia. Forty five patients (70%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen). Four cycles of standard dose (175mg/m2, 37 patients) or higher dose (250 mg/m2, 27 patients) of paclitaxel (day 1) with ifosfamide 1.2 g/m2 (day 1-5) and cisplatin 20 mg/m2 (day 1-5) were given 21 days apart with G-CSF support, followed by resection of resectable radiographic residua. Results: Nineteen of 37 (51%) patients treated with standard dose of paclitaxel achieved favourable response (complete remission or partial remission with negative serum tumor markers) compared to 20 of 27 (74%) patients treated with higher dose of paclitaxel (p = 0.07). In median follow-up of 23.9 months 37 patients (58%) experienced disease relapse and 33 (52%) patients died. Patients treated with higher dose of paclitaxel had better progression-free survival (median: not reached vs. 7 months, HR = 0.54, 0.28 - 1.04; p = 0.06) and overall survival (median: not reached vs. 33 months, HR = 0.69, 0.34-1.39; p = 0.31) compared to patients treated with standard dose of paclitaxel. Conclusions: Our data support the hypothesis that higher dose of paclitaxel with ifosfamide and cisplatin is associated with better outcome compared to standard dose of paclitaxel in patients with relapsed GCTs treated in first relapse.

Paclitaxel, Ifosfamide, and Cisplatin Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Cancer

2000 ◽  
Vol 18 (12) ◽  
pp. 2413-2418 ◽  
Author(s):  
Robert J. Motzer ◽  
Joel Sheinfeld ◽  
Madhu Mazumdar ◽  
Manjit Bains ◽  
Tania Mariani ◽  
...  
Keyword(s):  
Germ Cell ◽  
Salvage Therapy ◽  
Complete Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Testicular Germ Cell ◽  
Primary Tumor Site ◽  
Prognostic Features ◽  
Line Therapy ◽  
Response To Chemotherapy

PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m2, and cisplatin 100 mg/m2 were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m2; the largest dose was selected for the phase II part of the trial. RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity. CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.

Neoadjuvant combination immunotherapy with pembrolizumab and high dose IFN-α2b in locally/regionally advanced melanoma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 181-181 ◽  
Author(s):  
Ahmad A. Tarhini ◽  
Yan Lin ◽  
Joseph J. Drabick ◽  
Rogerio Izar Neves ◽  
Marc S. Ernstoff ◽  
...  
Keyword(s):  
Response Rate ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Clinical Activity ◽  
High Dose ◽  
Risk Patients ◽  
Definitive Surgery ◽  
Pathologic Complete Response Rate ◽  
One Year

181 Background: Neoadjuvant pembrolizumab at 200 mg in combination with high dose IFNα2b (HDI) for locally/regionally advanced or recurrent melanoma may improve the clinical outcomes of these high risk patients (pts), and provide access to blood and tumor pre/post pembro-HDI to illuminate the host effector and suppressor immune mechanisms. Methods: Pts were treated with pembro 200 mg IV every 3 weeks (wk) x 2 doses followed by definitive surgery, then every 3 wks for up to one year. HDI (20 MU/m²/d IV x 5 days (d)/wk for 4 wks then 10 MU/m²/d SC every other d TIW for 48 wks) was given concurrently. Tumor samples were obtained at baseline and at definitive surgery (wk 6-8) and serum/PBMC at baseline, 6 wks, 3, 6, 12 months (mo). Results: Twenty evaluable pts (14 male, 6 female, 14 cutaneous primary, 4 unknown, 3 mucosal), age 29-82 were treated. 5 had Stage IIIB (N1b, N2b, M2c), 11 IIIC (N3) and 4 IV (M1a, M1b) melanoma. Over 230 cycles have been delivered to date (median 14). Worst toxicities included grade (Gr) 3: fatigue (8; 40%), ↑CPK (5; 25%), hypophosphatemia (5; 25%), ↑lipase (3; 15%), lymphopenia (3; 15%), hypertension (2; 10%), diarrhea/colitis (1; 5%), arthralgia (1, 5%), syncope (1, 5%), hyponatremia (1, 5%), neutropenia (1; 5%), anemia (1, 5.00%) nausea (2, 10%), flu like symptoms (1, 5%). There were 3 Gr 4 events (CPK, hyperglycemia, lymphopenia). One suspected grade 5 event occurred 6 months after completion of therapy with autopsy evidence of pneumonia and myocarditis. Among 20 evaluable pts, 4 relapsed and 1 died. Median follow-up for pts who have not relapsed is 11 months. The radiologic preoperative response rate (WHO; unconfirmed) was 65%. The pathologic complete response rate (no viable tumor on histologic assessment) was 35%. Conclusions: Neoadjuvant pembro-HDI exhibited promising clinical activity. Longer follow up is underway in order to define the long term benefits and risks. Clinical trial information: NCT02339324.

Bortezomib Consolidation Following Upfront ASCT for Multiple Myeloma Deepens Disease Response and MRD-Negative Rate without Compromising Response to Subsequent Bortezomib Salvage: Results of a Phase II Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4508-4508 ◽  
Author(s):  
Oliver C Cohen ◽  
Neil Rabin ◽  
Nicholas Counsell ◽  
Roger G Owen ◽  
Bilyana Popova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Phase Ii ◽  
Salvage Therapy ◽  
Progression Free Survival ◽  
Patient Choice ◽  
High Dose ◽  
Cell Transplant ◽  
Second Line ◽  
Disease Response

Abstract Background: Consolidation after high dose therapy and autologous stem cell transplant (ASCT) for multiple myeloma (MM) can improve response depth and prolong progression free survival (PFS), but it is important to ensure good quality of life (QoL) and responsiveness to further salvage therapy. We conducted a single-arm Phase II weekly bortezomib consolidation trial (BCT) to assess outcomes in MM patients receiving upfront ASCT. Methods: Bortezomib-na•ve patients with at least stable disease at 3-4 months post-high dose melphalan 200mg/m2 with ASCT received up to 8 cycles of bortezomib (1.3mg/m2 days 1,8,15,22 in a 4-week cycle), 17 intravenously (IV) and 23 subcutaneously (SC). The primary endpoint was disease response (IMWG) at 6 and 12 months post-ASCT. Other endpoints were MRD by multiparametric flow cytometry (patient 15 onwards) at 6 and 12 months post-ASCT, toxicity, PFS, overall survival, osteoblast function and Qol (EORT-QLQ-C30). Serum basic alkaline phosphatase (bALP) and ostocalcin (OC) were measured by ELISA. Results: The study recruited 40 patients between December 2009 and March 2014 at a median of 3.4 months post-ASCT. The median age was 61 years (range 43-69); 55% male; isotypes were: 22 (59%) IgG, 9 (24%) IgA, 1 (3%) IgD, 5 (14%) light chain only, 1 non-secretory and 2 unknown. Induction regimens pre-ASCT were thalidomide (33, 87%), idarubicin and dexamethasone (5, 13%). and unknown in 2. One patient was withdrawn prior to commencement (unfit for treatment) and 3 patients stopped trial treatment after 1 cycle (2 toxicity, 1 disease progression). Of 36 patients who completed >1 cycle of bortezomib, 10 stopped treatment early (5 toxicity, 4 patient choice, 1 disease progression); median number of cycles received was 8. Eleven (28%) patients experienced a total of 15 grade 3 adverse events (AE); 6 (neuropathy, 3 in IV group, 18% cf 3 in SC group, 13%), 4 (infection), 1 (fatigue), 2 (haematological), 2 other. One patient had a grade 4 infection (cycle 1, treatment discontinued) and 1 grade 4 back pain. EORTC-QLQ-C30 scores for global health status and physical, emotional and social functioning did not change significantly throughout treatment. After a median follow up of 44.4 months, 18 (45%) are alive without progression, 20 (50%) are alive with progression and 2 (5%) died after progression. BCT improved response depth in assessable patients who completed >1 cycle (n=34). Disease response at trial entry: 4 (12%) sCR/CR, 19 (56%) VGPR, 10 (29%) PR, 1(3%) SD, cf. response at 12 months post-ASCT: 7 (21%) sCR/CR, 22 (65%) VGPR, 4 (12%) PR, 1(3%) PD. Biochemical response depth improved in 12 patients. 19 patients had MRD testing at 3 (where available) or 6 months post-ASCT and again at 12 months, 10 were MRD+ at the earlier time point, of whom 4 converted to MRD- at 12 months. Of the 9 MRD- patients, all remained negative at 12 months. 15 patients (44%) had improvement in biochemical and/or MRD response at 12 months. Median PFS was 38.5 months (95%CI 29.1-47.9)(Figure). Patients who were MRD- at 12 months had median PFS of 49.2 months (95%CI 35.3-63.2) compared with 22.0 months (95%CI 21.5-22.6) in MRD+ patients (p=0.03). Of the 22 patients who relapsed, 12 received bortezomib-based salvage regimens, 5 received carfilzomib-based regimens and 5 have not started second-line therapy. Disease responses in patients receiving bortezomib salvage was 8 (67%) VGPR, 4 (33%) PR. Four patients went on to have a 2nd ASCT. In the 17 patients receiving salvage, median 2nd PFS from start of second line was 14.8 months (95%CI 8.2-18.0). At 3 months post-ASCT, levels of the osteoblast markers bALP and OC were significantly higher in CR/VGPR patients, compared to patients with PR or less (p=0.04 and 0.03, respectively). Neither marker changed significantly following BCT. Conclusions: For patients with MM, consolidation with weekly bortezomib post-ASCT is well tolerated and deepens disease response and MRD negativity without compromising the response to subsequent bortezomib-based salvage therapy. Patients who are MRD- at 12 months enjoy a median PFS of 4 years. This low intensity post-ASCT strategy deserves further study in the context of current and evolving protocols for newly diagnosed patients. Figure Figure. Disclosures Yong: Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor; Janssen: Research Funding.

scholarly journals Subcutaneous Anti-D versus intravenous methylprednisolone for the treatment of immune thrombocytopenic purpura

2018 ◽  
Vol 5 (5) ◽  
pp. 1719
Author(s):  
Olia Sharmeen ◽  
Mohammod Hasanur Rashid ◽  
Md Abdur Rouf ◽  
Afiqul Islam
Keyword(s):  
Platelet Count ◽  
Single Dose ◽  
Immune Thrombocytopenic Purpura ◽  
Hemoglobin Concentration ◽  
Complete Response ◽  
Response To Treatment ◽  
High Dose ◽  
Thrombocytopenic Purpura ◽  
Methyl Prednisolone ◽  
Change Response

Background: Established treatment option for immune thrombocytopenic purpura (ITP) are intravenous immunoglobulin (IVIg), anti-D immunoglobulin’ and high dose intravenous methyl prednisolone (HIVMP). The present study was undertaken to compare the efficacy of subcutaneous bolus anti-D over HIVMP in the treatment of ITP.Methods: A randomized clinical trial was conducted on a total 20 children with ITP, presented with extensive bleeding manifestation and platelet count <20 × 109/L;10 children received single dose subcutaneous anti-D (75 microgram/kg) and 10 children received HIVMP (30 mg/kg/dose) for 3 consecutive days. Patients were monitored for response to treatment and adverse events, platelet count and hemoglobin label were done in all patients at 24-hour, 48-hour, 72 hour, 1st week, 2nd week, 1st month, 2nd month and 3rd month after treatment to observe the change. Response rate define as a platelet count over 20 × 109/L within 72 hours of treatment. All the data were analyzed with the help of SPSS software version 16.0.Results: By 24 hours of treatment 40% patient of anti-D and 10% patients of HIVMP group had platelet count >20 x109/L, by 72 hours 90% patients of both group achieved complete response (P =1.750). In HIVMP group the rate of remission gradually decreasing but in anti-D group it was persistently remain high. In anti-D group hemoglobin concentration decreased in 80% cases (P=0.023) but rate of decrease was not significant. New hemorrhage or significant extension of hemorrhage did not observe in any group.Conclusions: A single dose of subcutaneous anti-D raised platelet count in children with ITP more rapidly and effectively than HIVMP (30 mg/kg/dose) with an acceptable safety profile.

Lenalidomide in Combination with Dexamethasone Is More Effective Than Dexamethasone at First Relapse in Relapsed Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3552-3552 ◽  
Author(s):  
Edward Stadtmauer ◽  
Donna Weber ◽  
M. Dimopolous ◽  
Andrew Belch ◽  
Michel Attal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Response Rate ◽  
Response Rates ◽  
High Dose ◽  
Cell Transplant ◽  
Second Line ◽  
Prior Therapy ◽  
First Relapse ◽  
Line Of Therapy

Abstract Background: High-dose dexamethasone (Dex) remains a standard therapy for relapsed or refractory multiple myeloma (MM). Lenalidomide is a novel, orally administered, immunomodulatory drug (IMiD) that has single-agent activity against MM and additive effects when combined with Dex. At the interim analysis, lenalidomide/dexamethasone achieved a significant benefit over dexamethasone, providing a longer median time to progression (TTP), higher response rates, and higher CR rates. Aim: This prospective subgroup analysis of MM-009/010 was performed to determine the potential benefit of starting lenalidomide/dexamethasone at first relapse by analyzing outcomes with lenalidomide/dexamethasone versus dexamethasone among patients who had received only 1 versus > 1 prior line of therapy. Methods: Patients who had received at least 1 prior treatment and were not refractory to dexamethasone were randomized to either receive oral lenalidomide (25 mg daily for 3 weeks every 4 weeks) plus Dex (40 mg on Days 1–4, 9–12, 17–20 every 4 weeks for 4 months, then 40 mg on Days 1–4 every cycle thereafter) or placebo plus Dex. The European Blood and Marrow Transplantation criteria were used to evaluate response. Randomization was stratified at entry by number of prior therapies (1 versus > 1). Results: Among the 248 patients who had received only 1 prior therapy, those receiving second-line lenalidomide/dexamethasone had a significantly longer median TTP (71 vs. 20 wks) and a higher response rate (complete response [CR] + partial response [PR]; 65% vs. 26%) versus those receiving second-line dexamethasone. Among the 456 patients who had received > 1 prior line of therapy, the median TTP (41 vs. 20 wks), response rate (58% vs. 20%) were higher with lenalidomide/dexamethasone compared with dexamethasone. Comparing patients who received lenalidomide/dexamethasone as second-line versus as later salvage therapy, the median TTP appeared longer and the response rates higher in patients who received lenalidomide/dexamethasone earlier, although TTP and response rates were also significantly better with lenalidomide/dexamethasone than with dexamethasone in patients who received lenalidomide/dexamethasone later. Differences in the groups included prior stem cell transplant (66% vs. 54%), thalidomide (12.5% vs. 53.2%), and bortezomib (0.4% vs. 11.6%) in the second-line versus later salvage therapy groups. No difference was observed in grade ¾ adverse events or survival with a median follow-up of 16.8 months. Conclusions: Lenalidomide/dexamethasone provided higher response rates and improved TTP compared with dexamethasone at first relapse and beyond. Response to lenalidomide/dexamethasone was superior to that to dexamethasone regardless of the type of prior therapy. TTP and response rates appeared more favorable when lenalidomide/dexamethasone was administered earlier at first relapse compared with its use as later salvage therapy. These data support the use of lenalidomide/dexamethasone for patients as second-line therapy.

Safety and preliminary activity of hydroxychloroquine and aldesleukin in metastatic renal cell carcinoma (mRCC): A cytokine working group study.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 440-440
Author(s):  
Leonard Joseph Appleman ◽  
Theodore F. Logan ◽  
Daniel Paul Normolle ◽  
Marc S. Ernstoff ◽  
Rahul Atul Parikh ◽  
...  
Keyword(s):  
Working Group ◽  
Interleukin 2 ◽  
Metabolic Stress ◽  
Complete Response ◽  
Protective Mechanism ◽  
High Dose ◽  
Cardiac Events ◽  
Cellular Autophagy ◽  
Clinical Responses ◽  
One Year

440 Background: Aldesleukin (recombinant human interleukin-2) has been an FDA-approved treatment for mRCC since 1992, based on a 5-10% rate of durable complete remissions. Autophagy is a protective mechanism that enables cells to survive the metabolic stress of cancer therapy. Hydroxychloroquine (HCQ) inhibits cellular autophagy and has shown synergy with interleukin-2 in animal tumor models. We hypothesized that this combination would be tolerable and active in patients with mRCC. Methods: The Cytokine Working Group initiated a study of high-dose aldesleukin in combination with oral HCQ for patients with mRCC. Subjects receive up to 6 cycles of aldeskleukin, 600,000 International Units per kg, on a standard schedule. HCQ is administered orally starting 2 weeks prior to the first dose of aldesleukin and continuing up to one year. The initial HCQ dose was 600 mg daily, with a planned dose escalation to 1200 mg daily after safety was demonstrated in five subjects. Subjects were monitored for safety and tolerability as well as response per RECIST 1.1. Results: Five subjects were treated at the first dose level of 600 mg daily HCQ plus aldesleukin with no unexpected toxicity. Thirteen subjects were then treated at HCQ 1200 mg daily with aldesleukin. Of these, two experienced hypotension and tachycardia and 1 patient died from pulmonary emboli. The cardiac events were consistent with aldesleukin toxicity, but were observed earlier in the course of treatment than anticipated for aldesleukin alone. HCQ dose was therefore de-escalated to 600 mg daily, and 8 additional subjects have been enrolled with no unexpected toxicity. In 26 of 39 planned subjects, there has been 1 complete response (CR) and 1 partial response (near CR), both in the 600 mg cohort. As of Oct 24, 2016, after a median of 36.6 months of follow-up, seven out of 26 subject have died, with median overall survival not yet obtained (95% C.I. = (29.6 months,unknown)). Conclusions: HCQ in combination with aldesleukin was found to be tolerable at a dose of 600 mg daily, with expected toxicities. Clinical responses have been observed. Clinical trial information: NCT01550367.

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