Bertuccelli M, Falcone A, Campoccia S, Conti M, Brunetti I, Caramella D, Giulianotti P C, Mosca F, Bartolozzi C, Conte P F
Sezione di Oncologia Medica, Ospedale di Livorno, Italy.
Tumori. 1999 Nov-Dec;85(6):473-7. doi: 10.1177/030089169908500609.
Intrahepatic continuous infusion FUDR induces a 50% response rate in patients with hepatic metastases from colorectal cancer. Lower rates have been observed in pretreated patients. The combination of floxuridine plus leucovorin has obtained over 70% responses, with high hepatic toxicity. The use of dexamethasone can decrease hepatic toxicity. A randomized study reported an increase in response rate and a decrease in hepatic toxicity in a group of patients treated with floxuridine plus dexamethasone compared to a group receiving only floxuridine. Moreover, the combination of mitomycin C, carmustine and floxuridine is also effective in pretreated patients.
On such premises, since July 1993 we have treated 39 patients affected by unresectable hepatic metastases from colon carcinoma (26 patients) and rectal carcinoma (13 patients) with the combination continuous infusion of floxuridine (0.20 mg/kg per day) + leucovorin (7.5 mg/m2/day) + dexamethasone (20 mg on days 1 to 14) and bolus mitomycin C (10 mg/m2 on day 1) via the hepatic artery. Cycles were administered every four weeks. There were as 28 males and 11 females, with a median age of 64 years (range, 39-75) and a median PS = 0. Twenty-two patients were pretreated with systemic chemotherapy including 5-fluorouracil plus leucovorin. Total number of cycles was 189, with a median of 6 cycles per patient (range, 1-12).
Of 39 patients 37 were assessable for response (2 patients were not assessable because they stopped chemotherapy for occlusion of the catheter after the first cycle). There were 3 complete responses (1 in a naive patient and 2 in pretreated patients), 16 partial responses (11 in pretreated patients and 5 in chemonaive patients), 4 minor responses, 4 stable disease and 10 progressive disease. The overall response rate was 51.3% (95 Cl, 51.3-86.7%). Median time to progression was 6 months (range, 1-34+). Overall survival was 18 months (range, 1-34+). Of 39 patients, 36 were assessable for toxicity (WHO) (3 patients died after the first cycle for progression of disease): diarrhea and nausea-vomiting grade 3-4 occurred respectively in 15 (41%) and 3 patients (8%); hepatic toxicity was mild.
The treatment we used showed an elevated activity in liver metastases from colorectal cancer even in patients pretreated and resistant to systemic chemotherapy, although toxicity grade 3-4 diarrhea occurred in approximately 40% of the patients.
肝内持续输注氟尿苷对结直肠癌肝转移患者的有效率为50%。在经预处理的患者中观察到较低的有效率。氟尿苷加亚叶酸钙的联合方案有效率超过70%，但肝毒性较高。地塞米松的使用可降低肝毒性。一项随机研究报告称，与仅接受氟尿苷治疗的组相比，接受氟尿苷加地塞米松治疗的一组患者有效率增加且肝毒性降低。此外，丝裂霉素C、卡莫司汀和氟尿苷的联合方案对经预处理的患者也有效。
基于上述情况，自1993年7月起，我们采用肝动脉持续输注氟尿苷（0.20mg/kg/天）+亚叶酸钙（7.5mg/m²/天）+地塞米松（第1至14天20mg）及推注丝裂霉素C（第1天10mg/m²）的联合方案治疗39例不可切除的结肠癌（26例）和直肠癌（13例）肝转移患者。每四周进行一个周期的治疗。患者中男性28例，女性11例，中位年龄64岁（范围39 - 75岁），中位体能状态评分为0。22例患者曾接受包括5-氟尿嘧啶加亚叶酸钙在内的全身化疗。总周期数为189个，每位患者的中位周期数为6个（范围1 - 12个）。
39例患者中37例可评估疗效（2例因在第一个周期后因导管阻塞停止化疗而不可评估）。有3例完全缓解（1例初治患者和2例经预处理患者），16例部分缓解（11例经预处理患者和5例初治患者），4例轻度缓解，4例病情稳定和10例病情进展。总有效率为51.3%（95%可信区间，51.3 - 86.7%）。中位疾病进展时间为6个月（范围1 - 34 +个月）。总生存期为18个月（范围1 - 34 +个月）。39例患者中36例可评估毒性（世界卫生组织标准）（3例患者在第一个周期后因疾病进展死亡）：3 - 4级腹泻和恶心 - 呕吐分别发生在15例（41%）和3例患者（8%）；肝毒性较轻。
我们使用的治疗方案对结直肠癌肝转移显示出较高活性，即使是对全身化疗预处理且耐药的患者，尽管约40%的患者出现3 - 4级腹泻毒性。
