Gornet J M, Azoulay D, Lévi F, Yovine A, Misset J L, Goldwasser F
Service de Cancérologie, Hôpital Paul Brousse, Villejuif, France.
Anticancer Drugs. 2000 Apr;11(4):263-8. doi: 10.1097/00001813-200004000-00006.
Three active antitumor agents, i.e. 5-fluorouracil (5-FU), oxaliplatin and CPT-11, are available for the treatment of advanced colorectal cancer (CRC) patients and have been successfully combined in two-drug regimens. Hence, CRC has become a chemosensitive disease, but the optimal combination of these agents in first-line treatment remains to be determined. We report the first case of the combination of CPT-11 with oxaliplatin, 5-FU and folinic acid (FA) as first-line chemotherapy for a patient with a pre-occlusive sigmoid adenocarcinoma and synchronous bulky liver metastases. CPT-11 was given at 125 mg/m2, prior to the start of a chronomodulated 4-day infusion of oxaliplatin 25 mg/m2/day, 5-FU 800 mg/m2/day and FA 300 mg/m2/day repeated every 2 weeks. The doses could be escalated to 150 mg/m2 for CPT-11 and 900 mg/m2/day for 5-FU. After six cycles of chemotherapy 70% reduction in tumor size was documented in the liver. The primary tumor was no longer detectable by barium enema. The toxicity included three episodes of grade 4 neutropenic fever, and two episodes of severe diarrhea and vomiting with dehydration. A cumulative grade 2 neurosensory toxicity was observed after six cycles. Following surgery of the primary tumor, because of the major hepatic tumor response and of the absence of extra-hepatic metastases, the patient might be registered for a liver transplantation program. This first report of combining the three active agents in CRC every 2 weeks led to a high dose intensity of each agent and was associated with a dramatic tumor response of a very advanced disease in a patient with already altered performance status. The antitumor activity in this patient suggests that a three-drug intensified regimen might be feasible and active. A prospective study appears warranted to further examine the efficacy and toxicity of this therapeutic approach, and to determine whether it may increase the fraction of advanced CRC patients becoming resectable. This aggressive chemotherapy program may contribute to a re-examination of the usefulness of liver transplantation in patients with metastatic CRC confined to the liver.
三种活性抗肿瘤药物，即5-氟尿嘧啶（5-FU）、奥沙利铂和伊立替康（CPT-11），可用于治疗晚期结直肠癌（CRC）患者，并且已成功联合用于两药方案。因此，CRC已成为一种对化疗敏感的疾病，但这些药物在一线治疗中的最佳联合方案仍有待确定。我们报告了首例将CPT-11与奥沙利铂、5-FU和亚叶酸（FA）联合作为一线化疗方案，用于一名患有乙状结肠腺癌伴阻塞前病变及同时存在巨大肝转移的患者。CPT-11的给药剂量为125mg/m²，在开始进行为期4天的时辰调节输注之前给药，奥沙利铂剂量为25mg/m²/天，5-FU剂量为800mg/m²/天，FA剂量为300mg/m²/天，每2周重复一次。CPT-11的剂量可增至150mg/m²，5-FU的剂量可增至900mg/m²/天。化疗六个周期后，肝脏肿瘤大小缩小了70%。钡剂灌肠检查未再发现原发性肿瘤。毒性反应包括3次4级中性粒细胞减少性发热、2次严重腹泻和呕吐伴脱水。六个周期后观察到累积2级神经感觉毒性反应。在原发性肿瘤手术后，由于肝脏肿瘤有显著反应且无肝外转移，该患者可能符合肝移植计划登记条件。这篇关于每2周将三种活性药物联合用于CRC的首例报告，使每种药物都具有高剂量强度，并与一名身体状况已改变的非常晚期疾病患者的显著肿瘤反应相关。该患者的抗肿瘤活性表明，三药强化方案可能可行且有效。一项前瞻性研究似乎很有必要，以进一步研究这种治疗方法的疗效和毒性，并确定其是否可能增加晚期CRC患者可切除的比例。这种积极的化疗方案可能有助于重新审视肝移植在局限于肝脏的转移性CRC患者中的实用性。
