プリチデプシン

危険有害性情報のコード(GHS)

• 絵表示(GHS)

  

• 注意喚起語

  Danger

• 危険有害性情報

  H225：引火性の高い液体および蒸気

  H319：強い眼刺激

• 注意書き

  P210：熱/火花/裸火/高温のもののような着火源から遠ざ けること。－禁煙。

  P233：容器を密閉しておくこと。

  P240：容器を接地すること/アースをとること。

  P241：防爆型の電気機器/換気装置/照明機器/．．．機器を使 用すること。

  P242：火花を発生させない工具を使用すること。

  P243：静電気放電に対する予防措置を講ずること。

  P261：粉じん/煙/ガス/ミスト/蒸気/スプレーの吸入を避ける こと。

  P264：取扱い後は皮膚をよく洗うこと。

  P264：取扱い後は手や顔をよく洗うこと。

  P270：この製品を使用する時に、飲食または喫煙をしないこ と。

  P271：屋外または換気の良い場所でのみ使用すること。

  P280：保護手袋/保護衣/保護眼鏡/保護面を着用するこ と。

  P301+P312：飲み込んだ場合：気分が悪い時は医師に連絡する こと。

  P303+P361+P353：皮膚（または髪）に付着した場合：直ちに汚染された衣 類をすべて脱ぐこと/取り除くこと。皮膚を流水/シャワー で洗うこと。

  P304+P340：吸入した場合：空気の新鮮な場所に移し、呼吸しやすい 姿勢で休息させること。

  P305+P351+P338：眼に入った場合：水で数分間注意深く洗うこと。次にコ ンタクトレンズを着用していて容易に外せる場合は外す こと。その後も洗浄を続けること。

  P321：特別な処置が必要である（このラベルの．．． を見よ）。

  P330：口をすすぐこと。

  P337+P313：眼の刺激が続く場合：医師の診断/手当てを受けること。

  P370+P378：火災の場合：消火に．．．を使用すること。

  P403+P235：換気の良い場所で保管すること。涼しいところに 置くこと。

  P501：内容物/容器を．．．に廃棄すること。

プリチデプシン 化学特性,用途語,生産方法

• 効能

  抗悪性腫瘍薬

• 説明

  Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin?. Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents.

• 生物活性

  Plitidepsin is a cytotoxic peptide originally found in the sea squirt Aplidium albicans. It interacts with a protein (eEF1A2) which is overexpressed in some cancers. This interaction leads to apoptosis. Synthetically produced plitidepsin has been found to have antiproliferative effects on cancer cells. Phase II trials have investigated its activity in tumours such as lung cancer, melanoma and multiple myeloma.

• 作用機序

  Plitidepsin induces apoptosis in multiple myeloma cells, which involves activation of p38 and c-jun NH(2)-terminal kinase signaling, Fas/CD95 translocation to lipid rafts, and ultimately caspase activation. The investigational agent also decreases the proliferation of multiple myeloma cells, an effect mediated by the suppression of several proliferative genes.In a pivotal phase III trial of patients with relapsed or refractory multiple myeloma, plitidepsin in combination with dexamethasone (Dex) significantly reduced the risk of progression or death compared to Dex alone.Plitidepsin has been approved by TGA in Australia for the treatment of multiple myeloma in combination with dexamethasone for patients that relapse after three lines of treatment, including proteasome inhibitors or immunomodulators.

• 臨床応用

  Plitidepsin is a cyclic depsipeptide isolated from the marine tunicate Aplidium albicans. Plitidepsin displays a broad spectrum of antitumor activities, inducing apoptosis by triggering mitochondrial cytochrome c release, initiating the Fas/ DC95, JNK pathway and activating caspase 3 activation. This agent also inhibits elongation factor 1-a, thereby interfering with protein synthesis, and induces G1 arrest and G2 blockade, thereby inhibiting tumor cell growth.A phase II prospective open-label study (Ferme et al. 2008 ) to evaluate its activity in patients with relapsed/ refractory non-cutaneous PTCL was conducted in 14 patients. They were treated with plitidepsin 3.2 mg/m 2 IV infusion over 1-h on days 1, 8 and 15 every 4 weeks. Eleven patients were evaluable when preliminary results were reported, one was too early and two were non-evaluable. One con fi rmed CR and 3 PR’s were observed with a 36% objective response rate. Median overall survival was 11 months.
  Plitidepsin was tolerable in this heavily pretreated population with low hematological toxicity. Transient but reversible ALT elevation was noticed in 7 patients.
  Future trials will establish its role in T-cell lymphoma.

• 安全性プロファイル

  Plitidepsin's safety profile has been extensively studied over both phase I and II/III trials, with the drug presenting mostly transient and tolerated adverse events. Myalgia, alanine aminotransferase/aspartate aminotransferase, creatine phosphokinase increase, fatigue, nausea, and vomiting constituted the most common dose-limiting toxicities in phase I studies. The same adverse events were reported regarding phase II/III studies, along with mild to moderate hematologic abnormalities, such as anaemia and thrombocytopenia. A hypersensitivity reaction was also observed; the event was well-tolerated, except one patient was withdrawn from a trial due to a grade 4 hypersensitivity reaction and hypotension. Notably, plitidepsin with dexamethasone was related to less hepatic enzyme abnormalities compared to plitidepsin alone, while a study assessing the combination of plitidepsin with dexamethasone and bortezomib reported no dose-limiting adverse events[1].

プリチデプシン 生産企業

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