大腸癌の標準的薬物治療の成り立ちと現状について  [in Japanese] An overview of chemotherapy and current topics for colorectal cancer in Japan  [in Japanese]

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Author(s)

    • 田村 孝雄 Tamura Takao
    • 神戸大学医学部附属病院消化器内科 Division of Digestive Diseases/Gastrointestinal Oncology, Kobe University Hospital

Abstract

消化管癌の内科的治療の最近の進歩は目覚しく, 進行大腸癌においても有効な薬剤が以前ではfluorouracil (5-FU) のみであったが, 近年になってirinotecan (CPT-11, カンブト<SUP>TM</SUP>, トポテシン<SUP>TM</SUP>) やoxaliplatin (L-OHP, エルプラット<SUP>TM</SUP>) といった新しい有効な薬剤が開発され, ここ数年は第一選択とすべき治療法が毎年のように更新されている。そして現在の大腸癌に対する各レジメンの生存期間延長への寄与は5-FU/LV=irinotecan<IFL<FOLFOX=FOLFIRIの順になると考えられており, irinotecanやoxaliplatinと5-FUの併用レジメンであるFOLFIRIとFOLFOXの2つのレジメンが第一選択の標準とすべき治療とされる。さらにこれらのレジメンが開発される過程において, 5-FUの持続点滴とbolus静注の違いや, 5-FUとirinotecanの相互作用などいくつかの薬物動態に関する内容も明らかとなってきた。<BR>最近ではuracil/tegafur (UFT<SUP>TM</SUP>), S-1 (TS-1<SUP>TM</SUP>), capecitabine (Xeloda<SUP>TM</SUP>) などの経口制癌薬の開発も進み, FOLFOXやFOLFIRIのレジメンのなかに含まれる5-FUの持続点滴を, 利便性の面からもこれらの経口薬で置き換える試みがなされつつある。加えてvascular endothelial growth factor (VEGF) やepidermal growth factor receptor (EGFR) などの働きを阻害するbevacizumab, cetuximabなどの分子標的治療薬もヒトでの使用が可能となり, それらも併用することで進行大腸癌の50%生存期間は2年に達しようとしている。<BR>化学療法を行わなかった場合の進行大腸癌の生存期間がおよそ3~6カ月という事実より考えて大腸癌に対する積極的薬物療法の意義が明らかになってきている。

Many dramatic advances have been made recently in the treatment of gastrointestinal cancer. For advanced colorectal cancer, fluorouracil (5-FU), long the only mainstay of chemotherapy, has been joined by new, effective anticancer agents such as irinotecan (CPT-11) and oxaliplatin (L-OHP). First-line chemotherapy has been refined continuously and updated annually. The latest regimens in order of survival benefits are 5-FU/LV=irinotecan<IFL<FOLFOX=FOLFIRI. FOLFIRI and FOLFOX, which consist of 5-FU/LV combined with irinotecan and oxaliplatin, are considered the latest first-line chemotherapy for advanced colorectal cancer. In the course of their development, aspects of their metabolism and pharmacology, and the relative advantages of 5-FU administration by continuous infusion or bolus administration, have been clarified.<BR>The introduction of orally administered drugs such as UFTTM, TS-1TM, and capecitabine are likely to further improve the results of 5-FU therapy. Their potential role, impact, and convenience as replacements for intravenously administered drugs, which include FOLFIRI and FOLFOX, are attracting attention. Bevacizumab and cetuximab, which inhibit the effect of VEGF or EGFR, have also become available. Their use for combination treatment is expected to increase median survival time to as much as two years.<BR>Median survival time for advanced colorectal cancer patients not treated with chemotherapy is somewhere between three and six months. This makes the value of chemotherapy for colorectal cancer beyond dispute.

Journal

  • Japanese Journal of Chemotherapy

    Japanese Journal of Chemotherapy 54(3), 232-238, 2006

    Japanese Society of Chemotherapy

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