75 research outputs found
A phase 2, multicenter, openâlabel study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma
Survivin is a microtubuleâassociated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a firstâinâclass survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6âmonth progressionâfree survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m2) in combination with YM155 (5 mg/m2 per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6âmonth PFS rate. Secondary endpoints were objective response rate (ORR), 1âyear overall survival (OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixtyâfour patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m2 and 56 patients received 75 mg/m2 of docetaxel. Sixâmonth PFS rate per Independent Review Committee (IRC) was 34.8% (n = 64; 95% CI, 21.3â48.6%), and per Investigator was 31.3% (n = 64; 95% CI, 19.5â43.9%). The best ORR (complete response [CR] + partial response [PR]) per IRC was 12.5% (8/64). The stable disease (SD) rate was 51.6% (33/64), leading to a CBR (CR + PR + SD) of 64.1% (41/64). Estimated probability of 1âyear survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6âmonth PFS rate â„20%) was not achieved.YM155 is a firstâinâclass agent that suppresses surviving. Though YM155 combined with docetaxel was generally wellâtolerated in this study, it showed limited efficacy in the treatment of metastatic melanoma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111757/1/cam4363.pd
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Ipilimumab administration for advanced melanoma in patients with pre-existing Hepatitis B or C infection: a multicenter, retrospective case series
Ipilimumab is a fully human, monoclonal antibody directed against Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) that has demonstrated a survival benefit and durable disease control in patients with advanced melanoma. Ipilimumab is associated with potentially serious immune-related adverse events, including autoimmune hepatitis. Because clinical trials of ipilimumab excluded patients with pre-existing hepatitis B or C infection, there is a paucity of data on the safety of ipilimumab administration to that patient population. Here, we report the largest case series to date of patients with hepatitis B or C who received ipilimumab for advanced melanoma. Two of the nine patients described in this case series experienced fluctuations in their liver function tests (LFTs) and were subsequently treated with corticosteroids. Although this is a small series, the rate of hepatotoxicity appears similar to what has been seen in the general population treated with ipilimumab, and the ability to administer ipilimumab did not appear to be affected by concomitant hepatitis B or C infection. The use of ipilimumab in patients with metastatic melanoma who have pre-existing hepatitis can be considered among other therapeutic options
Pegylated Interferon for the Adjuvant Treatment of Melanoma: FDA Approved, but What Is Its Role?
The article by Herndon and colleagues on the approval of peginterferon-alfa-2b for the adjuvant treatment of patients with resected node-positive melanoma, published in this issue of The Oncologist, is examined, and the relevance of this therapy in clinical practice discussed
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