進行性肝細胞癌にイリノテカンの肝動脈注入と陽子線治療が有効であった

Advanced hepatocellular carcinoma treated effectively with irinotecan via hepatic arterial infusion followed by proton beam therapy.

抄録

48歳，男性，肝動脈注入療法（HAI）後に陽子線治療を行った肝細胞癌の症例について報告する．この患者のHCC病変は直径88mmで、肝右葉に門脈腫瘍血栓を伴っていた。最初に5-フルオロウラシル、シスプラチン、イソボリンをHAIで投与し、インターフェロンαを併用し、その後エピルビシンとマイトマイシンCをHAIで投与した。しかし、いずれの治療法も明確な有効性は認められませんでした。その後，HAIによるイリノテカンの3週間連続投与により，腫瘍径は68mmに縮小した。しかし，腫瘍縮小から3ヵ月後，腫瘍は直径100mmに増大し，肝内転移が顕著となった。血管造影の結果，肝細胞癌は右肝動脈だけでなく，左胃動脈，右・左下脾動脈からも栄養を受けていることが判明した．動脈を再編成し、イリノテカンとハイパーサーミアのHAI化学療法を3ヶ月継続した結果、腫瘍径は50mmに縮小した。固形がんに対する効果判定基準による主腫瘍の縮小率は43％であり，本治療の有効性は部分奏効と判定された。腫瘍縮小から2ヶ月後、血清αフェトプロテイン（AFP）値が上昇したため、イリノテカンに代えてドセタキセルをHAIで投与した。ドセタキセル投与中、AFP値は抑制されたものの肝腫瘍は徐々に肥大化した。陽子線治療が開始され，治療後，肝腫瘍は壊死を示した．肝細胞癌発症から6年後、肝不全と遠隔転移により死亡した。本例は、HAIによるイリノテカン投与と陽子線治療が有効であり、腫瘍の抑制と長期生存が確認された最初の症例報告である。

We report a 48-year-old man with hepatocellular carcinoma (HCC) treated with hepatic arterial infusion (HAI) chemotherapy followed by proton beam therapy. The HCC lesion in this patient was 88 mm in diameter, with portal vein tumor thrombosis in the right lobe of the liver. He was first treated with 5-fluorouracil, cisplatin, and isovorin, administered by HAI, combined with interferon-alpha, and he was subsequently treated with epirubicin and mitomycin-C administered by HAI. However, no definite efficacy of either of these treatments was observed. Then, after 3 weeks' continuous administration of irinotecan by HAI, the tumor size decreased to 68 mm in diameter. However, 3 months after reduction of the tumor, the tumor had become enlarged to 100 mm in diameter and intrahepatic metastases were prominent. Angiographic findings indicated that the HCC was fed not only from the right hepatic artery but also from the left gastric and right and left subphrenic arteries. After rearrangement of the arteries, and 3 months' continuous HAI chemotherapy with irinotecan, plus hyperthermia, the tumor size had decreased to 50 mm in diameter. The reduction rate of the main tumor according to the Response Evaluation Criteria in Solid Tumors was 43%; therefore, the efficacy of this treatment was judged as a partial response. Two months after reduction of the tumor, the patient's serum alpha-fetoprotein (AFP) level was elevated, and so docetaxel was administered by HAI instead of irinotecan. The liver tumors showed gradual enlargement during the administration of docetaxel, although the AFP level was suppressed. Proton beam therapy was instituted and the liver tumors showed necrosis after this therapy. The patient died of hepatic failure and distant metastases 6 years after the onset of HCC. As far as we know, this is the first case report of HCC treated effectively with irinotecan administered by HAI followed by proton beam therapy in which tumor suppression and the long-term survival of the patient were observed.