Chronomodulated (Chrono) vs constant (Cst) rate infusional 5-fluorouracil (FU) with or without cisplatin (CDDP) in patients with advanced or metastatic pancreatic cancer. A multicenter randomized trial of the Chronotherapy Group of the European Organisation for Research and Treatment of Cancer (EORTC 05962)

4117 Background: Tolerability and activity of 5-day (d) infusional FU-oxaliplatin were improved with Chrono as compared with Cst in colorectal cancer pts(Levi et al, Lancet 1997). CDDP addition to FU tended to prolong Progression-Free Survival (PFS) in pancreatic cancer pts(Ducreux et al, Ann Oncol 2002). Methods: A factorial design tested the relative effects of CDDP addition (100 mg/m2/course, c) to FU (c1/c2/c3 : 5/6/6.5 g/m2) and Cst vs Chrono (FU : 10 pm-10 am, peak at 4 am; CDDP : 10 am-10 pm, peak at 4 pm) 5 d q21d. Pts with advanced (25) or M (82) histologically-proven pancreatic cancer were registered in 15 centers. CTC toxicity was assessed q10 d and response q 3c. Survival was the main endpoint. Results: Characteristics : CDDP no/yes, 55/52 pts; Chrono no/yes, 54/53 pts; median age, 63 y; WHO PS 0/1/2, 35/52/20 pts; M sites 0/1/2+, 16/51/36 pts. CDDP increased median PFS from 2.1 months (mo.) [95% CL, 1.9–2.3] to 3.2 mo. [2.5–5.0] and median survival from 5.4 mo. [3.9–8.4] to 8.3 mo. [5.7–11.9]...