Abstract
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.