Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer--a multi-centre randomised phase II study

Abstract

Background: No standard treatment for locally advanced pancreatic cancer (LAPC) is defined.

Patients and methods: Within a multi-centre, randomised phase II trial, 95 patients with LAPC were assigned to three different chemoradiotherapy (CRT) regimens: patients received conventionally fractionated radiotherapy of 50 Gy and were randomised to concurrent 5-fluorouracil (350 mg m(-2) per day on each day of radiotherapy, RT-5-FU arm), concurrent gemcitabine (300 mg m(-2)), and cisplatin (30 mg m(-2)) on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by sequential full-dose gemcitabine (1000 mg m(-2)) and cisplatin (50 mg m(-2)) every 2 weeks (RT-GC+GC arm). Primary end point was the overall survival (OS) rate after 9 months.

Results: The 9-month OS rate was 58% in the RT-5-FU arm, 52% in the RT-GC arm, and 45% in the RT-GC+GC arm. Corresponding median survival times were 9.6, 9.3, and 7.3 months (P=0.61) respectively. The intent-to-treat response rate was 19, 22, and 13% respectively. Median progression-free survival was estimated with 4.0, 5.6, and 6.0 months (P=0.21). Grade 3/4 haematological toxicities were more frequent in the two GC-containing arms, no grade 3/4 febrile neutropaenia was observed.

Conclusion: None of the three CRT regimens tested met the investigators' definition for efficacy; the median OS was similar to those previously reported with gemcitabine alone in LAPC.

Figure 1

CONSORT diagram.

Figure 2

(A) Progression-free survival by treatment arm. (B) Overall survival by treatment arm. Abbreviations: 5-FU, 5-fluorouracil; C, cisplatin; G, gemcitabine; RTX, radiotherapy.