JP7169297B2 - 再発膠芽腫(rgbm)の治療方法 - Google Patents
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Description
オーストラリアから来た47歳男性患者が、右頭頂後頭部GBMの亜全摘出を受けた後、テモゾロマイド(TMZ)と放射線の併用治療を受けた。治療後のMRI検査によってRGBMが示された。患者は、複数の標的化剤を併用したANP治療を開始した。6.3g/kg/日のA10および0.2g/kg/日のAS2-1を含むANP治療組成物が約8ヶ月間患者に静脈内投与された。同時に、ダサチニブ(0.5mg/kg/日)、エベロリムス(0.1mg/kg/日)、およびパゾパニブ(2.1mg/kg/日)が、標準投与量に対して50%~80%減量した投与量で患者に経口投与された。同時に、ベバシズマブ(7.5mg/kg)が2週間ごとに患者に静脈内投与された。約26日の治療の後、MRI検査を実施したところ、測定可能な増強病状は示されなかった。54日の治療の後、次のMRI検査を実施したところ、すべての増強病状の消失が示された。約84日の治療の後、PET/CTスキャンを実施したところ、代謝的に活性な病状は示されなかった。55日後、患者はオーストラリアに帰国した。患者の現在の状態はわかっていない。
オーストラリアから来た男性患者が、右側頭葉、頭頂葉、後頭葉、および脳梁を含むGBMの切除術を受けた後、テモゾロマイド(TMZ)と放射線の併用治療を受けた。上記治療の完了から2週間後、患者は2回目の切除術としてRGBMの外科的切除術を受けた。その後、MRI検査によって5.2cm×4.3cmの腫瘍が示された。分子プロファイリングの補助のもと、PB、ベバシズマブ、エルロチニブ、ラパマイシン、およびTMZが患者に投与された。6週間の治療の後、再度MRIスキャンを実施したが、腫瘍の所見は見られなかった。患者は3年間以上無病状態を維持していたが、MRI検査によってRGBMが見つかった。患者はRGBMの切除術を受けたが、約1ヶ月後、MRI検査によって4.8cm2の右側頭増強腫瘤が示された。
23歳の女性患者が、グレード2、IDH1(-)の線維性星細胞腫と診断された。患者は腫瘍の切除術を受けたが、約1年以内に腫瘍が再発したことがMRI検査によって示された。約1ヶ月後に実施したMRI検査では、更なる進行が示された。約2ヶ月後、患者が2回目の腫瘍切除術を受けたところ、病理検査によって膠芽腫、非メチル化MGMT、野生型IDH1、およびBRAF変異が示された。患者は約42日間の補助放射線治療を受けた。14日後、患者にはPB(0.2g/kg/日)、ソラフェニブ(3.6mg/kg/日)、エベロリムス(0.09mg/kg/日)、ダサチニブ(0.9mg/kg/日)が経口投与され、同時にベバシズマブ(10mg/kg/日)が2週間ごとに静脈内投与された。治療前のMRI検査によって、2.5cm×2.0cmの造影増強病変が示された。治療開始から約3ヶ月後のフォローアップMRI検査では、再発腫瘍は示されず、約46日後の次のMRI検査では完全寛解が確認された。2日後、携帯輸液ポンプによるAS2-1の静脈内投与を含む同時ANP治療が患者の治療に追加された。ANP治療のAS2-1投与量は、250mL/時(0.34g/kg/日)で1日6回40mL(80mg/mL)まで漸増された。約3ヶ月後のフォローアップMRI検査によって、完全寛解の継続が示された。患者は、8ヶ月間治療を継続した。現在、患者は5ヶ月間治療から離れており、腫瘍のない状態が続いている。
甲状腺機能低下症および糖尿病の既往歴があるが、通常の健康状態であった71歳女性患者が、視力障害を発症した。MRI検査によって、左後頭部に6cm×3cmの大きな脳腫瘍が示された。患者は切除術を受け、病理検査によって膠芽腫とされた。予後不良のため、患者は放射線治療および細胞毒性化学療法を拒否した。患者は、複数の標的化剤を併用したANP治療を開始した。ANP治療は、鎖骨下静脈カテーテルおよび携帯輸液ポンプによるAS2-1の静脈内投与を含むものであった。ANP治療のAS2-1投与量は、250mL/時(0.34g/kg/日)で1日6回40mL(80mg/mL)まで漸増された。同時に、ダサチニブ(0.7mg/kg/日)、エベロリムス(0.07mg/kg/日)、およびパゾパニブ(3.2mg/kg/日)が患者に連日経口投与された。同時に、ベバシズマブ(10mg/kg)が2週間ごとに患者に静脈内投与された。ANP治療前のベースラインMRI検査によって術後腔縁部に1.0cm×0.6cmの造影増強小結節が示された。約40日の治療の後、フォローアップMRI検査を実施したところ、小結節の改善が示された。約75日の治療の後、次のMRI検査を実施したところ、完全寛解が確認され、術後腔が3.6cm×3.1cmから2.0cm×2.8cmに縮小したことが示された。患者は、口腔内の痛みのため何度も治療を中断した。その結果、103日後に腫瘍が再発し、患者は4ヶ月後に死亡した。
本開示の記述:
Claims (9)
- 治療を必要とする患者の多形性膠芽腫(GBM)または再発多形性膠芽腫(RGBM)を治療するための治療薬であって、
前記治療薬は、
(a)複数の外来アンチネオプラストンと、
(b)複数の標的化剤と
を組み合わせてなり、
前記複数の外来アンチネオプラストンは、約4:1の比率の合成フェニルアセチルグルタミンナトリウム(PG)および合成フェニルアセチルイソグルタミンナトリウム(iso-PG)、または約4:1の比率のフェニル酢酸(PN)およびフェニルアセチルグルタミン(PG)を含み、
前記複数の標的化剤は、ベバシズマブ、パゾパニブ、ソラフェニブ、ダサチニブ、およびエベロリムスからなる群から選択される2種以上の剤を含むことを特徴とする治療薬。 - 前記複数の外来アンチネオプラストンに約4:1の比率の合成PGおよび合成iso-PGが含まれる場合は、前記複数の外来アンチネオプラストンを約0.5g/kg/日から約20g/kg/日の投与量で前記患者への静脈内投与に供し、
前記複数の外来アンチネオプラストンに約4:1の比率のPNおよびPGが含まれる場合は、前記複数の外来アンチネオプラストンを約0.08g/kg/日から約0.6g/kg/日の投与量で前記患者への静脈内投与に供する、請求項1に記載の治療薬。 - 請求項1に記載の治療薬であって、
前記複数の外来アンチネオプラストンには、フェニルアセチルグルタミンナトリウム(PG)およびフェニルアセチルイソグルタミンナトリウム(iso-PG)が含まれ、
約0.4g/kg/日から約16g/kg/日のフェニルアセチルグルタミンナトリウム(PG)、および
約0.1g/kg/日から約4g/kg/日のフェニルアセチルイソグルタミンナトリウム(iso-PG)
の量で、前記複数の外来アンチネオプラストンを静脈内投与に供する、治療薬。 - 請求項1に記載の治療薬であって、
前記複数の外来アンチネオプラストンには、フェニル酢酸(PN)およびフェニルアセチルグルタミン(PG)が含まれ、
約0.064g/kg/日から約0.48g/kg/日のフェニル酢酸(PN)、および
約0.016g/kg/日から約0.12g/kg/日のフェニルアセチルグルタミンナトリウム(PG)
の量で、前記複数の外来アンチネオプラストンを静脈内投与に供する、治療薬。 - 前記複数の標的化剤は、(a)経口投与に供する、パゾパニブ、ソラフェニブ、ダサチニブ、およびエベロリムスからなる群から選択される2種以上の剤と、(b)静脈内投与に供する、ベバシズマブとを含む、請求項1に記載の治療薬。
- パゾパニブおよびソラフェニブを約1mg/kg/日から約12mg/kg/日の投与量で経口投与に供することと、
ダサチニブを約0.3mg/kg/日から約2.0mg/kg/日の投与量で経口投与に供することと、
エベロリムスを約0.03mg/kg/日から約0.15mg/kg/日の投与量で経口投与に供することと、
ベバシズマブを約2mg/kg/日から約15mg/kg/日の投与量で1週間から3週間ごとに静脈内投与に供することとで、
前記複数の標的化剤を投与に供する、請求項1に記載の治療薬。 - 前記複数の外来アンチネオプラストンならびに前記パゾパニブ、ソラフェニブ、ダサチニブ、およびエベロリムスを少なくとも8週間連日投与に供し、前記ベバシズマブを1週間から3週間ごとに少なくとも8週間静脈内投与に供する、請求項1に記載の治療薬。
- 前記GBMまたはRGBMのサブタイプは、Classical型またはProneural型である、請求項1に記載の治療薬。
- (a)前記患者は、前記複数の外来アンチネオプラストンおよび前記複数の標的化剤の使用前に、少なくとも1の放射線治療、および/またはテモゾロマイド(TMZ)および/またはベバシズマブ(BVZ)を含む少なくとも1の化学療法治療の結果、客観的奏効が得られなかった患者である、または(b)前記患者は、前記複数の外来アンチネオプラストンおよび前記複数の標的化剤の使用前に、神経膠腫の切除術を受けた患者である、請求項1に記載の治療薬。
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