ANOTHER DOUBLET FAILURE FOR PANCREATIC CANCER

Phase III randomized trial comparing gemcitabine plus cisplatin vs. single-agent gemcitabine in chemotherapy-naive patients with advanced pancreatic cancer

21.10.09

Category: Scientific News

The GIP-1 (Gruppo Italiano Pancreas – GOIM/GISCAD/GOIRC) study

Single-agent gemcitabine remains standard first-line treatment for patients with advanced pancreatic cancer (APC). The Gruppo Italiano Pancreas (GIP)-1 phase III trial compared the combination of gemcitabine and cisplatin vs. gemcitabine alone. Results were presented at the Annual Meeting of American Society of Clinical Oncology held this year in Orlando, USA and during Plenary session of the AIOM 11th National Congress of Medical Oncology, Milan, Italy (10-13 October, 2009) by lead author, Dr Giuseppe Colucci of the Istituto Tumori “Giovanni Paolo II”, Ospedale Oncologico di Bari.

Patients with locally advanced and/or metastatic pancreatic cancer, age 18-75, Karnofsky Performance Status (KPS) ≥50, were randomized to receive gemcitabine (arm A) or gemcitabine + cisplatin (arm B). No maximum number of cycles was planned. Primary endpoint was overall survival (OS). To have 80% power of detecting a 0.74 Hazard Ratio (HR) of death (corresponding to increase in median OS from 4.8 to 6.5 months), with bilateral alpha=0.05, 400 patients were planned and 355 deaths were required. Clinical benefit, objective response rate (ORR), progression-free survival (PFS), toxicity and quality of life were secondary endpoints.

From April 2002 to April 2007, 400 patients were enrolled (A:199, B; 201) in 46 Italian institutions. Median age was 63 years (range 35-75), 59% males, 84% stage IV, 83% KPS ≥80. Median OS was 8.3 vs. 7.2 months in arm A and B, respectively; median PFS 3.9 vs. 3.8 months in arm A and B; and ORR 10.1% in arm A and 12.9% in arm B (none significantly important). Clinical benefit was experienced by 23.0% in arm A and 15.1% in arm B (p=0.057). Combination chemotherapy produced more anaemia (50% vs 39%, G3: 5% vs 1%), more neutropenia (44% vs 36%, G3&4: 25% vs 14%) and more thrombocytopenia (57% vs 29%, G3&4: 16% vs 5%). No relevant differences were seen in non-haematological toxicity.

The authors concluded that weekly combination of gemcitabine and cisplatin as first-line treatment of APC failed to demonstrate any improvement compared to single-agent gemcitabine.