Cerny T, Martinelli G, Goldhirsch A, Terrier F, Joss R, Fey M F, Brunner K W, Küpfer A
Institut für Medizinische Onkologie, Universität Bern, Inselspital, Switzerland.
J Cancer Res Clin Oncol. 1991;117 Suppl 4(Suppl 4):S135-8. doi: 10.1007/BF01613218.
Phase II studies on ifosfamide and mesna in pancreatic cancer have mostly been inconclusive. In all of these studies ifosfamide was administered as an i.v. bolus or by short infusions. Since dose fractionation of ifosfamide over several days increases its therapeutic index, we chose to maximize the dose fractioning by selecting a continuous-infusion schedule (1.75 g/m2 on days 1-5 every 21-28 days, with mesna 60%-100% of the ifosfamide dose up to 12 h after ifosfamide). Since 1987 29 patients (performance status less than or equal to 2) with advanced inoperable adenocarcinoma of the pancreas were studied (8 women and 21 men; median age 58 years: 36-73 years). A total of 25 patients are evaluable for response (1 ineligible; 3 inevaluable: 2 early deaths due to disseminated intravascular coagulation, 1 refusal). One female patient with a complete response on computed tomography scan (after five cycles) but residual liver metastases on surgical exploration survived for 473 days. Three male patients with partial response survived for 205, 335 and 355 days. Six more patients with minor response (3) or no change (3) but significant decrease of tumour marker CA 19-9 had a median survival of 213 days (106-243). Responders seemed to benefit in terms of pain relief and general well-being. The median overall survival of all patients was 148 days (21-473). Haematotoxicity was rarely dose-limiting [median nadirs: white blood cells = 2.1 x 10(9)/l (0.45-6.4), Hb = 10.7 g/dl (7.5-13), platelets = 137 x 10(9)/l (21-411)]. Nausea and vomiting were mild with prophylactic oral metoclopramide. No central nervous system toxicity or urotoxicity was observed. Alopecia was seen in all patients who had received at least two cycles. Continuous infusion of ifosfamide was generally well tolerated and useful for palliation in 10 of 25 patients. A higher dose intensity is recommended.
异环磷酰胺和美司钠用于胰腺癌的II期研究大多没有定论。在所有这些研究中，异环磷酰胺均通过静脉推注或短时间输注给药。由于异环磷酰胺分几天进行剂量分割可提高其治疗指数，我们选择通过连续输注方案（每21 - 28天的第1 - 5天给予1.75 g/m²，美司钠剂量为异环磷酰胺剂量的60% - 100%，在异环磷酰胺给药后长达12小时）来最大化剂量分割。自1987年以来，对29例（体能状态小于或等于2）无法手术切除的晚期胰腺腺癌患者进行了研究（8名女性和21名男性；中位年龄58岁：36 - 73岁）。共有25例患者可评估疗效（1例不符合条件；3例不可评估：2例因弥散性血管内凝血早期死亡，1例拒绝治疗）。1例女性患者在计算机断层扫描上显示完全缓解（五个周期后），但手术探查时有残留肝转移，存活了473天。3例部分缓解的男性患者分别存活了205天、335天和355天。另外6例有轻微缓解（3例）或病情无变化（3例）但肿瘤标志物CA 19 - 9显著下降的患者中位生存期为213天（106 - 243天）。缓解者在疼痛缓解和总体健康状况方面似乎有所获益。所有患者的中位总生存期为148天（21 - 473天）。血液毒性很少成为剂量限制因素[中位最低点：白细胞 = 2.1×10⁹/L（0.45 - 6.4），血红蛋白 = 10.7 g/dl（7.5 - 13），血小板 = 137×10⁹/L（21 - 411）]。预防性口服甲氧氯普胺后，恶心和呕吐症状较轻。未观察到中枢神经系统毒性或泌尿系统毒性。所有接受至少两个周期治疗的患者均出现脱发。异环磷酰胺连续输注一般耐受性良好，25例患者中有10例从中获得姑息治疗效果。建议采用更高的剂量强度。
