Price Timothy J, Ross Paul J, Hickish Tamas, Tait Diana, Norman Andy R, Ford Hugo E R, Middleton Gary, Sumpter Kate, Hill Mark, Oates Jacqui, Cunningham David
Gastrointestinal Unit, Royal Marsden Hospital, London, UK.
Clin Colorectal Cancer. 2004 Feb;3(4):235-42. doi: 10.3816/CCC.2004.n.004.
The combination of protracted venous infusion (PVI) fluorouracil (5-FU) and mitomycin-C has previously been shown to be superior to PVI 5-FU alone in terms of response rate and failure-free survival. This study explores the effect of dose intensification by circadian timing of 5-FU in this combination on response, toxicity, and survival. Patients with advanced colorectal carcinoma were randomized to receive PVI 5-FU 300 mg/m2 daily or circadian-timed infusion (CTI) of 5-FU, beginning at 600 mg/m2 and subsequently reduced to 450 mg/m2, delivered as a flat-rate infusion from 10:15 PM to 9:45 AM. Both groups received mitomycin-C at a dose of 7 mg/m2 given every 6 weeks. From April 1996 to August 1998, 320 patients were randomized, including 263 with metastatic disease and 21 with circumferential margin involvement. The overall response rate for the PVI 5-FU group was 38%, compared with 30.3% for the CTI group (P = 0.176). There was no statistically significant difference in terms of failure-free survival (8.0 months vs. 9.9 months; P = 0.131) or overall survival (15.8 months vs. 16.3 months; P = 0.275) between the treatment groups. There were no differences in global quality of life. Grade 3/4 diarrhea occurred significantly more frequently with CTI 5-FU (6.5% vs. 19.8%; P < 0.001); a nonsignificant trend toward increased incidences of grade 3/4 infection and palmar plantar erythema were observed with CTI 5-FU. This study confirms the high response rate and overall survival figures for the combination of PVI 5-FU and mitomycin-C in colorectal cancer. However, dose intensification of 5-FU using a circadian-timed, flat-rate infusion did not lead to improved response or survival.
先前已证明，持续静脉输注（PVI）氟尿嘧啶（5-FU）与丝裂霉素-C联合使用在缓解率和无病生存期方面优于单独使用PVI 5-FU。本研究探讨了在该联合治疗方案中，通过5-FU的昼夜节律给药时间进行剂量强化对缓解、毒性和生存的影响。晚期结直肠癌患者被随机分为两组，一组每天接受PVI 5-FU 300mg/m²，另一组接受5-FU的昼夜节律定时输注（CTI），起始剂量为600mg/m²，随后减至450mg/m²，从晚上10:15至次日上午9:45匀速输注。两组均每6周接受一次剂量为7mg/m²的丝裂霉素-C治疗。1996年4月至1998年8月，320例患者被随机分组，其中263例患有转移性疾病，21例有环周切缘受累。PVI 5-FU组的总缓解率为38%，而CTI组为30.3%（P = 0.176）。治疗组之间在无病生存期（8.0个月对9.9个月；P = 0.131）或总生存期（15.8个月对16.3个月；P = 0.275）方面无统计学显著差异。生活质量整体上无差异。CTI 5-FU组3/4级腹泻的发生率显著更高（6.5%对19.8%；P < 0.001）；观察到CTI 5-FU组3/4级感染和手足红斑的发生率有增加趋势，但无统计学意义。本研究证实了PVI 5-FU与丝裂霉素-C联合治疗结直肠癌的高缓解率和总生存数据。然而，使用昼夜节律定时匀速输注进行5-FU剂量强化并未改善缓解或生存情况。
