Final analysis of a multicenter, randomized phase II trial comparing three different chemoradiotherapy regimens in the treatment

2009 ASCO Annual Meeting

J Clin Oncol 27:15s, 2009 (suppl; abstr 4610)

R. Wilkowski, S. Boeck, S. Ostermaier, R. Sauer, M. Herbst, R. Fietkau, M. Flentje, C. J. Bruns, H. G. Rau, V. Heinemann; Klinik Bad Trissl, Oberaudorf, Germany; Klinikum Grosshadern, University of Munich, Munich, Germany; University of Erlangen, Erlangen, Germany; University of Regensburg, Regensburg, Germany; University of Rostock, Rostock, Germany; University of Würzburg, Würzburg, Germany; Klinikum Dachau, Dachau, Germany

Abstract:

Background: To date, no standard treatment approach for patients (pts) with non-resectable, locally advanced pancreatic cancer (PC) is defined.

Methods: Within a prospective phase II trial treatment-naive pts with locally advanced PC and adequate organ function were randomly assigned to three different CRT regimens; all pts received a conventionally fractionated radiotherapy of 50 Gy (with a daily dose of 2.0 Gy) and were randomized to either concurrent 5-FU as a 24h-infusion (350 mg/m²/d on each day of radiotherapy, RT-5FU arm), concurrent low-dose gemcitabine 300 mg/m² and cisplatin 30 mg/m² on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by a sequential chemotherapy with full- dose gemcitabine (1000 mg/m²) and cisplatin (50 mg/m²) every two weeks (RT-GC+GC arm). Treatment duration in the RT- GC+GC arm was upon disease progression or unacceptable toxicity. The primary study endpoint was the overall survival (OS) rate after 9 months (mo); secondary endpoints included response rate (WHO criteria), progression-free survival (PFS), resectability and toxicity.

Results: Ninety-five patients (median age 64 years, 54% male, 50% KPS 90-100%) were recruited from 12 German centers. Seventy patients were evaluable for objective response: the intent-to-treat response rate (CR+PR) was 19% in the RT-5FU arm, 22% in the RT-GC arm and 13% in the RT-GC+GC arm, respectively. Overall, 18 pts (19%) underwent surgical resection after initial CRT (R0 in 8 pts). After a median follow-up of 8.6 mo, median PFS was estimated with 4 mo (RT-5FU), 5.6 mo (RT-GC) and 6 mo (RT- GC+GC), respectively (p=0.21). The corresponding median OS times were 9.6 mo, 9.3 mo and 7.3 mo (p=0.61). Hematological grade 3/4 toxicities were higher in the two gemcitabine/cisplatin-containing arms, but no grade 3/4 febrile neutopenia was observed. Regarding non-hematological toxicity, nausea/vomiting were more frequently in the RT-GC and RT-GC+GC arm, whereas diarrhea was more frequent in the RT-5FU arm.

Conclusions: Based on these data, gemcitabine/cisplatin-based CRT does not achieve a higher clinical efficacy compared to RT-5FU, and is associated with increased hematological toxicity.