Analysis of prognostic factors in patients with advanced pancreatic cancer: Subgroup analysis of a randomized phase III trial comparing single-agent gemcitabine to the gemcitabine plus cisplatin combination

PurposeThis phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2twice daily on days 1 to 14 plus Gem 1,000 mg/m2by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent.ResultsA total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms.ConclusionGemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.4433 ◽

2010 ◽

Vol 28 (10) ◽

pp. 1645-1651 ◽

Cited By ~ 198

Author(s):

Giuseppe Colucci ◽

Roberto Labianca ◽

Francesco Di Costanzo ◽

Vittorio Gebbia ◽

Giacomo Cartenì ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Single Agent ◽

Advanced Pancreatic Cancer ◽

Phase Iii ◽

Hematologic Toxicity ◽

Line Treatment ◽

First Line ◽

Phase Iii Trial ◽

First Line Treatment

PurposeSingle-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).Patients and MethodsPatients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) ≥ 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m2weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m2added 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 α .05, 355 events were needed and 400 patients planned.ResultsFour 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 ≥ 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.ConclusionThe addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.

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477 pERK Expression in Erlotinib-treated Patients with Advanced Pancreatic Cancer: a Translational Subgroup Analysis From the Randomized AIO-PK0104 Phase III Trial

European Journal of Cancer ◽

10.1016/s0959-8049(12)72275-x ◽

2012 ◽

Vol 48 ◽

pp. 148

Author(s):

S. Boeck ◽

S. Ormanns ◽

R.P. Laubender ◽

A. Jung ◽

J.T. Siveke ◽

...

Keyword(s):

Pancreatic Cancer ◽

Subgroup Analysis ◽

Advanced Pancreatic Cancer ◽

Phase Iii ◽

Phase Iii Trial ◽

Perk Expression

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Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2004.10.112 ◽

2004 ◽

Vol 22 (8) ◽

pp. 1430-1438 ◽

Cited By ~ 554

Author(s):

E. Van Cutsem ◽

H. van de Velde ◽

P. Karasek ◽

H. Oettle ◽

W.L. Vervenne ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Single Agent ◽

Survival Rates ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Phase Iii ◽

Controlled Study ◽

Double Blind ◽

Free Survival

Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m2 intravenously weekly × 7 for 8 weeks, then weekly × 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade ≥ 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.

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