Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study.
OBJECTIVE
Single-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696).


METHODS
Patients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) > or = 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m(2) weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m(2) added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral alpha .05, 355 events were needed and 400 patients planned.


RESULTS
Four hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS > or = 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity.


CONCLUSIONS
The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.
Colucci
Giuseppe
G
Medical and Experimental Oncology Unit, Oncology Institute Giovanni Paolo II, Bari, Italy.
Labianca
Roberto
R
Di Costanzo
Francesco
F
Gebbia
Vittorio
V
Cartenì
Giacomo
G
Massidda
Bruno
B
Dapretto
Elisa
E
Manzione
Luigi
L
Piazza
Elena
E
Sannicolò
Mirella
M
Ciaparrone
Marco
M
Cavanna
Luigi
L
Giuliani
Francesco
F
Maiello
Evaristo
E
Testa
Antonio
A
Pederzoli
Paolo
P
Falconi
Massimo
M
Gallo
Ciro
C
Di Maio
Massimo
M
Perrone
Francesco
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000093542:Gemcitabine
D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine