Bajetta E, Di Bartolomeo M, Stani S C, Artale S, Ricci S B, Bozzetti F, Mazzaferro V, Toffolatti L, Buzzoni R
Operative Unit Medical Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Int J Radiat Oncol Biol Phys. 1999 Sep 1;45(2):285-9. doi: 10.1016/s0360-3016(99)00205-9.
The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer.
5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. External beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the end of treatment and explored for resection in cases of partial response (PR).
A total of 32 patients were treated between 1992 and 1997. Ab initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (range 36-71); performance status (PS) (ECOG): 0-1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders underwent surgical exploration, and radical resection was possible in 5. Three of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. The median survival time was 9 months for the entire group, and 1-year survival rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1-2 diarrhea was observed in 10 cases.
This preoperative regimen was feasible and led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.
与单纯放疗相比，局部不可切除胰腺癌患者采用放疗与氟尿嘧啶（5-FU）联合治疗可显著提高生存率。去氧氟尿苷（5-DFUR）是一种口服活性氟嘧啶，其细胞毒性代谢产物（5-FU）可能在肿瘤血管化程度高的区域聚集。本试验旨在改善局部区域控制并使不可切除胰腺癌患者的病变可切除。
5-DFUR以500mg/m²的剂量口服，每日两次，每两周服用4天，共四个疗程，每次服用5-DFUR前2小时口服亚叶酸25mg，每日两次。外照射放疗剂量为每周1000cGy，共3周，随后休息2周，然后再以每周1000cGy照射2周（总剂量5000cGy）。治疗结束后4周对患者进行重新分期，部分缓解（PR）的患者进行手术切除探查。
1992年至1997年间共治疗32例患者。剖腹手术（16例）或计算机断层扫描（16例）显示初始不可切除，27例因血管侵犯，9例因大量区域淋巴结转移，4例两者皆有。中位年龄为63岁（范围36 - 71岁）；体能状态（PS）（ECOG）：0 - 1 = 28例，PS 2 = 4例。所有患者均有可测量病灶且可评估疗效。有7例PR（22%），10例SD（31%），15例PD（47%）。所有缓解者均接受手术探查，5例可行根治性切除。其中3例患者仍无疾病复发，随访时间分别为18、27和65个月；另外2例术后11和14个月复发。全组中位生存时间为9个月，1年生存率为31%。治疗从未因毒性而停止。无美国国立癌症研究所（NCI）CTC 3或4级毒性事件；10例观察到1 - 2级腹泻。
这种术前治疗方案可行，在16%原本无法手术的病例中成功实现了手术切除。中位生存期与5-FU输注联合放疗的结果相当。可切除率以及切除患者的生存获益，使得这些结果值得更大规模研究的证实。
