晚期结直肠癌患者中每周24小时持续输注5-氟尿嘧啶联合交替使用奥沙利铂或伊立替康的剂量探索性研究。

Dose-finding study of weekly 24-h continuous infusion of 5-fluorouracil associated with alternating oxaliplatin or irinotecan in advanced colorectal cancer patients.

作者信息

Cals L, Rixe O, François E, Favre R, Merad L, Deplanque G, Laadem A, Juin P, Bereder J M, Bernardini D, Herait P

机构信息

Fédération de Cancérologie des Etablissements Privés/Publics de la région PACA-Corse, Hôpital de la Timone, Marseille.

出版信息

Ann Oncol. 2004 Jul;15(7):1018-24. doi: 10.1093/annonc/mdh259.

DOI:10.1093/annonc/mdh259

PMID:15205194

Abstract

PURPOSE

To determine maximum tolerated dose, safety and efficacy of weekly 24 h infusional 5-fluorouracil (5-FU) combined alternately with oxaliplatin and irinotecan.

PATIENTS AND METHODS

Advanced colorectal carcinoma patients in first- or second-line chemotherapy received increasing doses of 5-FU (weekly 24 h continuous intravenous infusion without leucovorin) on days 1, 8, 15 and 22, irinotecan days 1 and 15; and oxaliplatin days 8 and 22, every 35 days.

RESULTS

Thirty-four patients received 175 cycles. The median age was 64 years (range 47-78). Eighteen per cent of patients had the primary tumor in the rectum, with a median of one disease site (range one to three), and liver involvement in 88% and lung in 38%. Six (18%) patients had chemotherapy for prior advanced disease. The most frequent grade 3-4 toxicity was neutropenia (41% of patients), but the regimen was well tolerated clinically, with febrile neutropenia in two patients and grade 4 neutropenia lasting >7 days in one; grade 3-4 diarrhea, nausea and vomiting in 6% of patients; grade 3-4 peripheral neuropathy in 9% of patients. Seventeen patients had a partial response (50%; 95% confidence interval 33%-67%), 13 had stable disease and one had progressive disease. Five patients underwent metastatic surgical resection after tumor shrinkage. Median response duration was 14 months (range 4.7-29.2+) and median time to progression was 11.3 months (range 1.1+-30.7+).

CONCLUSIONS

This combination three-drug regimen is feasible and well tolerated without toxicity overlap. Preliminary antitumor activity compares well with standard double combinations, with an unusually long median time to progression. The recommended dose is 5-FU 3000 mg/m(2), weekly for 4 weeks, irinotecan 100 mg/m(2) days 1 and 15, oxaliplatin 80 mg/m(2) days 8 and 22. Further assessment of antitumor activity and safety is warranted.

摘要

目的

确定每周24小时输注5-氟尿嘧啶（5-FU）交替联合奥沙利铂和伊立替康的最大耐受剂量、安全性和疗效。

患者与方法

一线或二线化疗的晚期结直肠癌患者在第1、8、15和22天接受递增剂量的5-FU（每周24小时持续静脉输注，不使用亚叶酸），伊立替康在第1天和第15天使用；奥沙利铂在第8天和第22天使用，每35天为一个周期。

结果

34例患者共接受了175个周期的治疗。中位年龄为64岁（范围47 - 78岁）。18%的患者原发肿瘤位于直肠，中位病灶数为1个（范围1 - 3个），88%的患者有肝脏转移，38%的患者有肺转移。6例（18%）患者曾接受过晚期疾病的化疗。最常见的3 - 4级毒性是中性粒细胞减少（41%的患者），但该方案临床耐受性良好，2例患者出现发热性中性粒细胞减少，1例患者4级中性粒细胞减少持续超过7天；6%的患者出现3 - 4级腹泻、恶心和呕吐；9%的患者出现3 - 4级周围神经病变。17例患者部分缓解（50%；95%置信区间33% - 67%），13例病情稳定，1例病情进展。5例患者在肿瘤缩小后接受了转移灶手术切除。中位缓解持续时间为14个月（范围4.7 - 29.2 +），中位疾病进展时间为11.3个月（范围1.1 + - 30.7 +）。

结论

这种三联药物方案可行且耐受性良好，无毒性叠加。初步抗肿瘤活性与标准双药联合方案相当，疾病进展中位时间异常长。推荐剂量为5-FU 3000 mg/m²，每周一次，共4周，伊立替康100 mg/m²在第1天和第15天使用，奥沙利铂80 mg/m²在第8天和第22天使用。有必要进一步评估其抗肿瘤活性和安全性。