Recchia F, Rea S, Nuzzo A, Lalli A, Di Lullo L, De Filippis S, Saggio G, Di Blasio A, Massa E, Mantovani G
Unita operative di Oncologia, Ospedale Civile di Avezzano, Universita degli studi de L'Aquila, Italy.
Oncol Rep. 2003 Jan-Feb;10(1):65-9.
In vitro and in vivo studies have shown that oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and leucovorin (L) have a synergistic activity on metastatic colorectal cancer (MCC). In order to better exploit the synergism of action between the three drugs, L-OHP was administered over 2 days, together with 5-FU-L, in a cohort of patients with MCC that had been pre-treated with chemotherapy. Forty-six patients were entered into the trial. All had been pre-treated with chemotherapy for metastatic disease: 14 with the 'de Gramont' regimen alone, and 32 with the same regimen combined with irinotecan (CPT-11). The outpatient treatment consisted of L-OHP 50 mg/m(2), followed immediately by the 'de Gramont' regimen. All drugs were administered on days 1 and 2, every 14 days. Median patient age was 65 years (range: 46-78), male/female ratio was 29/17. All 46 patients were evaluated for response and toxicity. We observed 1 complete response (2.2%) and 14 partial responses (30.4%), giving an overall response rate of 32.6% (95% CI: 19.5-48.06%); 22 patients had stable disease (47.8%) and 9 patients progressed (19.6%). After a median follow-up of 13 months, median time to progression was 6.4 months (range: 3.1-31.2+), while overall median survival was 12.2 months (range: 3.7-31.2+). Toxicity was manageable: grade 3 or 4 neutropenia was observed in 33% of patients, while only 6% of patients had grade 1-2 neurotoxicity. The fractionated bimonthly schedule of L-OHP plus 5-FU-L, showed activity, with an acceptable toxicity profile, both in patients with MCC pre-treated with the 'de Gramont' regimen alone, or with this regimen associated with CPT-11.
体外和体内研究表明，奥沙利铂（L-OHP）、5-氟尿嘧啶（5-FU）和亚叶酸（L）对转移性结直肠癌（MCC）具有协同活性。为了更好地利用这三种药物之间的协同作用，在一组接受过化疗预处理的MCC患者中，将L-OHP在2天内与氟尿嘧啶-亚叶酸（5-FU-L）联合给药。46例患者进入该试验。所有患者均接受过转移性疾病的化疗预处理：14例仅接受“德格拉蒙”方案治疗，32例接受相同方案联合伊立替康（CPT-11）治疗。门诊治疗包括L-OHP 50mg/m²，随后立即采用“德格拉蒙”方案。所有药物均在第1天和第2天给药，每14天重复一次。患者中位年龄为65岁（范围：46 - 78岁），男女比例为29/17。对所有46例患者进行了疗效和毒性评估。我们观察到1例完全缓解（2.2%）和14例部分缓解（30.4%），总缓解率为32.6%（95%CI：19.5 - 48.06%）；22例患者疾病稳定（47.8%），9例患者病情进展（19.6%）。中位随访13个月后，中位疾病进展时间为6.4个月（范围：3.1 - 31.2+），而总中位生存期为12.2个月（范围：3.7 - 31.2+）。毒性是可控的：33%的患者出现3或4级中性粒细胞减少，而只有6%的患者出现1 - 2级神经毒性。L-OHP加5-FU-L的分阶段双月给药方案，在仅接受“德格拉蒙”方案预处理的MCC患者，或接受该方案联合CPT-11治疗的患者中均显示出活性，且毒性特征可接受。
