Randomized Dose-Escalation Study Evaluating Peginterferon Alfa-2a in Patients With Metastatic Malignant Melanoma

2006 ◽  
Vol 24 (7) ◽  
pp. 1188-1194 ◽  
Author(s):  
Reinhard Dummer ◽  
Claus Garbe ◽  
John A. Thompson ◽  
Alexander M. Eggermont ◽  
Kisook Yoo ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Adverse Events ◽  
Response Rate ◽  
Randomized Study ◽  
Stage Iv ◽  
Metastatic Malignant Melanoma ◽  
Dose Escalation Study ◽  
Good Tolerability ◽  
Major Response ◽  
Peginterferon Alfa

Purpose A pegylated interferon, peginterferon alfa-2a (PEG-IFNα-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFNα. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFNα-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system). Patients and Methods PEG-IFNα-2a was administered subcutaneously at 180 (n = 48), 360 (n = 53), or 450 μg (n = 49) once weekly for 24 weeks, with maintenance therapy for responders. Efficacy was assessed by the proportion of patients with complete response (CR) or partial response (PR). Results The major response rate (CR or PR) was 6% in the 180-μg group (CR, 2%; PR, 4%), 8% in the 360-μg group (CR, 2%; PR, 6%), and 12% in the 450-μg group (CR, 6%; PR, 6%). The times to achieve a major response, duration of major response, rate of disease progression, and 12-month survival were similar between groups, although overall median survival was significantly different among the three groups (P = .0136). More patients required dose adjustment for safety reasons in the higher dose groups, but PEG-IFNα-2a was generally well tolerated, with few withdrawals because of adverse events (6%, 19%, and 16% in the 180-, 360-, and 450-μg groups, respectively). The most common adverse events were fatigue, pyrexia, and nausea. Conclusion PEG-IFNα-2a at doses up to 450 μg once weekly has shown good tolerability and similar efficacy to conventional IFNα and monochemotherapy in stage IV metastatic melanoma.

scholarly journals Cholecystectomy for Resistant Metastatic Malignant Melanoma of the Gallbladder: A Case Report

2020 ◽  
pp. 1-3
Author(s):  
Maria Julia Corbetta Machado ◽  
Costa Karihaloo ◽  
Maria Julia Corbetta Machado
Keyword(s):  
Malignant Melanoma ◽  
Metabolic Response ◽  
Open Cholecystectomy ◽  
Stage Iv ◽  
Metastatic Malignant Melanoma ◽  
Complete Metabolic Response ◽  
Resistant Disease ◽  
Stage Iv Disease ◽  
Malignant Melanoma Patient

Malignant melanoma is an unpredictable disease, known to metastasize early even in thin melanomas. Historically the presence of intraabdominal metastasis meant poor prognosis with a 5-year survival of less than 20%. That has significantly changed with effective systemic therapy (EST), with most recent studies reporting 5-year survival of up to 50%. Metastasecectomy for resistant disease has been considered in Stage IV disease, however there is very little literature on the combination of EST and metastasectomy. This report describes a case of Stage IV malignant melanoma patient who developed resistant disease within her gallbladder fundic wall. She underwent open cholecystectomy, with complete metabolic response at 1-year follow up PET.

Final safety results of BO17704 (AVAiL): A phase III randomized study of first-line bevacizumab (Bv) and cisplatin/gemcitabine (CG) in patients (pts) with advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8039-8039
Author(s):  
V. Hirsh ◽  
R. Ramlau ◽  
J. von Pawel ◽  
P. Zatloukal ◽  
G. Vera ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Randomized Study ◽  
Locally Advanced ◽  
Safety Data ◽  
Final Analysis ◽  
Phase Iii ◽  
Platinum Based Chemotherapy ◽  
Grade 3

8039 Background: AVAiL, an international placebo-controlled phase III trial, showed that Bv-based therapy significantly improved PFS and response rate in patients with advanced/recurrent NSCLC. This report summarizes overall safety findings from AVAiL. Methods: AVAiL randomized 1,043 patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC to C 80mg/m2 (d1) and G 1,250mg/m2 (d1 and d8) q3w for up to 6 cycles plus either Bv 7.5mg/kg q3w (n=331 with safety data), Bv 15mg/kg q3w (n=329) or placebo (n=326). Bv/placebo was administered until disease progression. Primary endpoint was PFS; secondary endpoints included OS, response rate, and safety. Safety was measured using NCI-CTC version 3.0 criteria for adverse events (AEs). Results: At final analysis, the median/maximum duration of Bv therapy was 4.9/28.5 mo (Bv 7.5) and 4.3/23.4 mo (Bv 15). The most common AEs overall were hematological and gastrointestinal (GI), and occurred in similar proportions of pts in the Bv and placebo arms. Grade ≥3 AEs occurred in 80%, 83%, and 77% of pts in the Bv 7.5, Bv 15 and placebo arms, respectively. The most common grade ≥3 adverse events were hematological, mainly neutropenia and thrombocytopenia. Neutropenia was reported in 43% (Bv 7.5), 40% (Bv 15) and 34% (placebo) of pts. Grade ≥3 AEs of special interest included hypertension (7%, 9% and 2%), proteinuria (2%, 3% and 0%), bleeding (4%, 5% and 2%) and hemoptysis (0.5%, 1.2% and 1.3%). The incidence of grade 5 hemoptysis was low (0.9%, 0.9% and 0% of pts, respectively). The incidence of GI perforations (<1%), thromboembolic events (≤8%), CHF (≤1%) and wound healing complications (<1%) was low and similar between treatment arms. The incidence of serious AEs was 39%, 45% and 36% in the Bv 7.5, Bv 15 and placebo arms, respectively. No new safety signals were reported. Conclusions: After E4599, AVAiL further demonstrated the efficacy of Bv in combination with platinum-based chemotherapy in the treatment of advanced NSCLC. Final safety data confirm the well established and manageable safety profile of Bv-based therapy in pts with advanced NSCLC. [Table: see text]

scholarly journals Multiple Metastatic Malignant Melanoma Presenting Intraluminal Gallbladder Bleeding

2014 ◽  
Vol 99 (5) ◽  
pp. 600-605 ◽  
Author(s):  
Hisashi Onozawa ◽  
Motonobu Saito ◽  
Sayaka Yoshida ◽  
Takeshi Sakuma ◽  
Masami Matsuzaki ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Multidisciplinary Treatment ◽  
Stage Iv ◽  
Immunohistochemical Analysis ◽  
Metastatic Malignant Melanoma ◽  
Unknown Primary ◽  
Pathologic Examination ◽  
Gallbladder Metastasis ◽  
Primary Origin ◽  
Unknown Primary Origin

Abstract We report a case of malignant melanoma of unknown primary origin presenting metastasis in various organs as well as intraluminal gallbladder bleeding due to gallbladder metastasis. A 58-year-old woman was diagnosed with stage IV metastatic malignant melanoma. Because she exhibited acute cholecystitis and hemobilia due to malignant melanoma of the gallbladder, laparoscopic cholecystectomy was performed to relieve the symptoms. The resected gallbladder specimen showed a pedunculated black mass indicating malignant melanoma. Pathologic examination and immunohistochemical analysis revealed malignant melanoma of the gallbladder. Only a few cases of gallbladder malignant melanoma presenting hemobilia have been reported; here we present our case, including the experience of multidisciplinary treatment.

scholarly journals Efficacy and Safety of Apatinib in Patients with Recurrent or Refractory Melanoma

2020 ◽  
Author(s):  
Shumin Yuan ◽  
Qiang Fu ◽  
Yingkun Ren ◽  
Zhimeng Li ◽  
Huijuan Wang ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Response Rate ◽  
Objective Response ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Metastatic Malignant Melanoma ◽  
Advanced Melanoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background: Prognosis of patients with metastatic malignant melanoma is very poor and partly due to high resistance to conventional chemotherapies. The study’s objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma.Methods: This was a single-arm, single-center phase II trial. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Eligible patients received at least one first-line therapy for advanced melanoma and experienced recurrence. Apatinib (500 mg) was orally administered daily. Trail registration: Clinical Trials, ID: NCT03383237. Registered on 24 December 2017. URL of trail registry record: https://register.clinicaltrials.gov. Results: Fifteen patients were included in the analysis. The median PFS was 4.0 months. There were two major objective responses, for a 13.33% response rate. Eleven patients had stable disease, with a DCR of 86.67%.The median OS was 12.0 months. The most common clinically significant grade 3 or 4 toxicities included hypertension and canker sore. No treatment-related deaths occurred.Conclusions: Apatinib showed antitumor activity as a second or first-line therapy in patients with malignant melanoma. The toxicity was manageable.

scholarly journals Efficacy and safety of apatinib in patients with recurrent or refractory melanoma

2020 ◽  
Author(s):  
Shumin Yuan ◽  
Qiang Fu ◽  
Yingkun Ren ◽  
Zhimeng Li ◽  
Huijuan Wang ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Response Rate ◽  
Objective Response ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Metastatic Malignant Melanoma ◽  
Advanced Melanoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Prognosis of patients with metastatic malignant melanoma is very poor and partly due to high resistance to conventional chemotherapies. The study’s objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma. Methods This was a single-arm, single-center phase II trial. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Eligible patients received at least one first-line therapy for advanced melanoma and experienced recurrence. Apatinib (500 mg) was orally administered daily. Trail registration: Clinical Trials, ID: NCT03383237. Registered on 24 December 2017. URL of trail registry record: https://register.clinicaltrials.gov. Results Fifteen patients were included in the analysis. The median PFS was 4.0 months. There were two major objective responses, for a 13.33% response rate. Eleven patients had stable disease, with a DCR of 86.67%.The median OS was 12.0 months. The most common clinically significant grade 3 or 4 toxicities included hypertension and canker sore. No treatment-related deaths occurred. Conclusions Apatinib showed antitumor activity as a second or first-line therapy in patients with malignant melanoma. The toxicity was manageable.

scholarly journals Effect and Safety of Ixazomib Plus Dexamethasone (ID) in Patients with Waldenstrom's Macroglobulinemia (WM): Real-World Evidences from a Single Center in China

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5265-5265
Author(s):  
Jiadai Xu ◽  
Zheng Wei ◽  
Jing Li ◽  
Jingli Zhuang ◽  
Lili Ji ◽  
...  
Keyword(s):  
Adverse Events ◽  
Overall Response Rate ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
International Workshop ◽  
B Cell Lymphoma ◽  
Clinical Activity ◽  
Primary Therapy ◽  
Overall Response ◽  
Major Response

Introdution: As a second-generation proteasome inhibitors (PIs), ixazomib has come to China for 1 years. PIs has been proved efficacy in patients with Waldenstrom macroglobulinemia (WM), a rare form of B-cell lymphoma. Aims: To evaluated the clinical activity and safety profile of combining ixazomib and dexamethasone (ID) in patients with WM, both in those who previous had not received systematic treatment and in those with refractory or relapsed disease (RRWM). Patients and Methods: The protocol therapy consisted of oral ixazomib, 4 mg, on days 1, 8, and 15, with oral dexamethasone, 10 mg, on days 1, 8, 15, and 22, every 4 weeks. Progression-free survival (PFS) was set as the primary end point. Response rates, sustained hematologic improvement from baseline, and safety were set as the key secondary end points. Responses were determined according to the 6th International Workshop WM response criteria. Adverse events (AEs) were reported by CTCAE v4.03. The data cut-off is 26 July 2019. Results: Under the premise of respecting the patient preferences, 9 symptomatic patients with WM have been enrolled, in whom 5 patients were newly diagnosed (NDWM) receiving ID as primary therapy (PT) and the other 4 patients were with RRWM having been received previous systematic therapies. All patients were included in this analysis. The baseline clinical characteristics and major therapy situations are summarized in Table 1. The median reaction time was 4.14 weeks, which was 4.00 weeks in WM patients receiving ID as PT and 7.00 weeks in RR WM patients. After a median follow-up of 6.03 months, in NDWM patients, the overall response rate was 80.0%, and the major response rate (CR+VGPR+PR) was 40.0% (2/5). Patients with RRWM were equally responsive. The overall response rate was 75.0%, and the major response rate (CR+VGPR+PR) was even relatively higher, which was 50.0% (2/4). The median PFS was not reached. The ID regimen was well tolerated with 66.7% patients reporting no drug related AE. Grade 1 adverse events reported in 3 patients included diarrhea (1/9, 11.1%), thrombocytopenia (1/9, 11.1%), digestive disturbance(1/9, 11.1%). Shingles (grade 2) was reported in 1 patient. Serum IgM decreased from 42.66 g/l (median) at baseline to 21.02 g/l (median) in NDWM patients (Fig. 1A), from 43.87 g/l (median) at baseline to 25.59g/l (median) in RRWM patients (Fig. 1B). The median level of hemoglobin in patients with a hemoglobin of less than 115.0 g/l before using ID increased from 71.6 g/dl (median) at baseline to 87.3 g/l in NDWM patients (Fig. 1C), from 73.7 g/dl (median) at baseline to 89.3 g/l in RRWM patients (Fig. 1D). There have been 2 cases suffered disease progression after receiving ID regimen. Conclusions: ID regimen offers a relatively effective and well tolerated choice for patients with WM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy and Safety of Orelabrutinib in Relapsed/Refractory Waldenstrom's Macroglobulinemia Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 46-46
Author(s):  
Daobin Zhou ◽  
Jie Jin ◽  
Zheng-zheng Fu ◽  
Shuhua Yi ◽  
Wei Li Zhao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adverse Events ◽  
B Cell ◽  
Response Rate ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Major Response ◽  
Grade 3 ◽  
Waldenström's Macroglobulinemia

Abstract Background Waldenstrom's Macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with immunoglobulin M (IgM) monoclonal gammopathy. Bruton's tyrosine kinase (BTK) plays a key role in signaling pathways for the survival of WM clone, particular in patients harboring MYD88 L265P mutations. However, due to target selectivity issue, Clinical uses of early BTK inhibitors are still compromised with off-target activities to many other kinases besides BTK. Orelabrutinib is a novel, highly potent small molecule inhibitor of BTK with superior selectivity for B-cell malignancies and autoimmune diseases. Preliminary efficacy and safety data of ICP-CL-00105 in relapsed/refractory WM patients are presented here. Methods ICP-CL-00105 is a single arm, multiple centers, open label, phase 2 study in clinical and histopathological confirmed patients with R/R WM requiring treatment per IWWM-7. MYD88 and CXCR4 mutations were assessed in bone marrow samples at baseline. Orelabrutinib at a daily dose of 150mg was administered orally until disease progression or unacceptable toxicity. Blood samples for IgM were assessed at baseline and every cycle for 6 cycles and every 3 cycles thereafter by central lab. Responses were assessed in accordance with IWWM-6 and NCCN guidelines. The primary endpoint was major response rate (MRR) as assessed by IRC. Key secondary endpoints were MRR as assessed by investigator, overall response rate (ORR), duration of major response (DOMR), progression-free survival (PFS), OS, changes in IgM levels from baseline, improvement on hemoglobin levels and safety. Treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs) were assessed according to NCI CTCAE v4.03. Results As of June 1, 2021, for the 47 patients the median follow-up duration was 10.5 months. The median age was 63 years (range, 56-68 years), 40 patients (85.1%) were male. 87.2% of patients were at intermediate or high risk according to the Prognostic Scores (IPSS). The proportion of patients with MYD88 L265PCXCR4 wildtype was 83% at baseline. With a median duration of treatment of 9.2 months, MRR was 74.5% as assessed by investigator. ORR was 87.2% with 97.9% patients achieved disease control. The estimated 12-month DOMR were 89.5%. The estimated 12-month PFS and OS were 88.0% and 92.3%, respectively. The median PFS and median OS have not been reached. The MRR was higher in patients with MYD88 L265PCXCR4 wildtype (79.5%). The median IgM level was 30.3g/L at baseline. The decline in the serum IgM levels from baseline were observed with a median reduction by 79.0% (IQR: -89.4, -57.2). The median hemoglobin level at baseline was 102g/L. Durable improvement in hemoglobin levels was found in 83% of patients with a median maximal improvement of 40g/L (IQR: 24.0, 62.0). Safety data were summarized by the cutoff date of June 1, 2021. The most commonly reported AEs were thrombocytopenia (27.7%)，neutropenia (14.9%), leukopenia (10.6%), upper respiratory infection (14.9%)，weight increased (14.9%), influenza-like disease (12.8%) and rash (10.6%). Most reported AEs (89.5%) were grade 1-2. 16 patients (34.0%) reported grade ≥ 3 TEAE while 9 patients (19.1%) reported grade ≥ 3 TRAE. There was no reported grade ≥3 atrial fibrillation and/or atrial flutter, or grade ≥3 diarrhea. Only One TRAE (2.1%) resulted in drug discontinuation. Conclusion Orelabrutinib has demonstrated substantial efficacy in treating r/r WM patients under short-term follow-up. It has shown favorable safety and tolerability profile with limited off-target adverse effects. It has the potential to be a promising treatment option for r/r WM patients. Disclosures Hu: Astellas Pharma, Inc.: Research Funding. Tian: Innocare pharma: Current Employment. Zhu: Innocare pharma: Current Employment. Zhang: Innocare pharma: Current Employment. Zhao: Innocare pharma: Current Employment. Zhang: Innocare pharma: Current Employment.

scholarly journals Efficacy and safety of apatinib in patients with recurrent or refractory melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22026-e22026
Author(s):  
Zibing Wang ◽  
Shumin Yuan ◽  
Xiaojie Zhang ◽  
Hao Huang ◽  
Quanli Gao
Keyword(s):  
Malignant Melanoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Metastatic Malignant Melanoma ◽  
Advanced Melanoma

e22026 Background: The prognosis of patients with metastatic malignant melanoma is very poor, a fact that is partly due to its high resistance to conventional chemotherapies. The objectives of this phase II trial were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma. Methods: This was a single arm, single center phase II trial. The primary endpoint was progression free survival (PFS), and the second endpoints was objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Eligible patients received at least one prior line of therapy for advanced melanoma and experienced recurrence. Apatinib was given daily at a dose of 500 mg orally. This study was registered at ClinicalTrials.gov , number NCT03383237 . Results: A total of 17 patients were included in the final analysis. The median PFS was 4.5 months. There were two major objective responses, for a response rate of 11.8%. Thirteen patients had a stable disease, for a DCR of 88.2%. The median OS was 11.5 months. The most common clinically significant grade 3 or 4 toxicities included hypertension (n = 1) and canker sore (n = 1). No treatment-related death occurred. Conclusions: Apatinib showed antitumor activity as a second or above line therapy in patients with malignant melanoma. The toxicity was manageable. Clinical trial information: NCT03383237.

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