Randomized Phase II Comparison of Dose-Intense Gemcitabine: Thirty-Minute Infusion and Fixed Dose Rate Infusion in Patients With Pancreatic Adenocarcinoma

2003 ◽  
Vol 21 (18) ◽  
pp. 3402-3408 ◽  
Author(s):  
Margaret Tempero ◽  
William Plunkett ◽  
Veronique Ruiz van Haperen ◽  
John Hainsworth ◽  
Howard Hochster ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Dose Rate ◽  
Pancreatic Adenocarcinoma ◽  
Median Survival ◽  
Phase Ii ◽  
Fixed Dose ◽  
Time To Treatment ◽  
Randomized Phase Ii ◽  
Fixed Dose Rate ◽  
Time To Treatment Failure

Purpose: To conduct a randomized phase II trial of dose-intense gemcitabine using a standard 30-minute infusion or the fixed dose rate (FDR) infusion (10 mg/m2/min) in patients with pancreatic adenocarcinoma. Patients and Methods: In this prospective trial, patients with locally advanced and metastatic pancreatic adenocarcinoma were treated with 2,200 mg/m2 gemcitabine over 30 minutes (standard arm) or 1,500 mg/m2 gemcitabine over 150 minutes (FDR arm) on days 1, 8, and 15 of every 4-week cycle. The primary end point of this trial was time to treatment failure. Secondary end points included time to progression, median survival, safety, and pharmacokinetic studies of gemcitabine. Results: Ninety-two patients were enrolled onto this study; 91% of the patients had metastatic disease. Time to treatment failure was comparable in both treatment groups; however, the median survival for all patients was 5.0 months in the standard arm and 8.0 months in the FDR arm (P = .013). For patients with metastases, the median survival was 4.9 months in the standard arm and 7.3 months in FDR arm (P = .094). The 1- and 2-year survival rates for all patients were 9% (standard arm) versus 28.8% (FDR; P = .014) and 2.2% (standard arm) versus 18.3% (FDR; P = .007), respectively. Patients in the FDR infusion arm experienced consistently more hematologic toxicity. Pharmacokinetic analyses demonstrated a two-fold increase in intracellular gemcitabine triphosphate concentration in the FDR arm (P = .046). Conclusion: Pharmacokinetic and clinical data in this trial supports the continued evaluation of the FDR infusion strategy with gemcitabine.

Phase II trial of neoadjuvant fixed dose rate (FDR) gemcitabine with capecitabine (GX) combination chemotherapy in locally advanced pancreatic adenocarcinoma (LAPA)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15553-e15553
Author(s):  
J. Lee ◽  
S. Lee ◽  
T. Kim ◽  
J. Lee ◽  
D. Park ◽  
...  
Keyword(s):  
Dose Rate ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Fixed Dose ◽  
Fixed Dose Rate ◽  
Locally Advanced Pancreatic Adenocarcinoma ◽  
Advanced Pancreatic Adenocarcinoma

e15553 Background: To determine the efficacy and safety of fixed dose rate (FDR) gemcitabine and capecitaibne (GX) combination chemotherapy for locally advanced pancreatic adenocarcinoma Methods: Patients with histologically confirmed LAPA were eligible for this prospective phase II trial. Dynamic pancreas/pelvic CT, MRI and FDG-PET were undertaken to assess the resectability. EUS was also performed as needed basis. ‘Borderline resectable (BR)’ and ‘unresectable (UR)’ criteria developed by our pancreatico-biliary multidisciplinary management team (PBMMT) and NCCN criteria were used. After confirmation of resectability, patients received 3 cycles of FDR gemcitabine 1,250 mg/m2 on D1 and D8 and capecitabine 950 mg/m2 from D1-D14 every 3 weeks. Thereafter, staging was repeated and patients underwent surgery if the disease was not unresectable. For patients with R0 resection, additional 6 cycles of GX were administered. For patients with R1 resection, chemoradiotherapy (CRT) (54 Gy over 5 weeks with concurrent 5-FU and leucovorin or capecitabine) followed by FDR-GX was administered. Patients with stable or better response to chemotherapy but assessed unresectable at reassessment received additional chemotherapy up to 9 cycles followed by CRT. Results: Between August 2006 and July 2008, 38 eligible patients (14 with BR and 24 with UR based on NCCN criteria; 29 with BR and 9 with UR based on our PBMMT criteria) entered on this study. The median age was 61 yo (42–76) and 71% had cT4 disease. The response to neoadjuvant chemotherapy was PR in 6 (16%), SD in 26 (68%) and PD in 3 (8%). Metabolic response was achieved in 20 patients (53%) with 2 metabolic CR out of 31 evaluable patients. Grade 3 or worse adverse effects were mainly HFS (n=5) and gastrointestinal (n=3) with no grade 4 in severity. Surgery was performed in 9 patients (24.0%, R0=8, R1=1, 6 in NCCN-BR and 3 in NCCN-UR, 9 in PBMMT-BR) and five patients refused surgery although their diseases seemed not to be unresectable. The median PFS was 9.4 months (95% CI, 8.3–10.4) and estimated median OS was 13.5 months (95% CI, 12.4- 14.5). Conclusions: FDR-GX was effective as neoadjuvnat chemotherapy in LAPA with favorable toxicity profile. No significant financial relationships to disclose.

scholarly journals Randomized Phase II Study of Gemcitabine Administered at a Fixed Dose Rate or in Combination With Cisplatin, Docetaxel, or Irinotecan in Patients With Metastatic Pancreatic Cancer: CALGB 89904

2009 ◽  
Vol 27 (33) ◽  
pp. 5506-5512 ◽  
Author(s):  
Matthew H. Kulke ◽  
Margaret A. Tempero ◽  
Donna Niedzwiecki ◽  
Donna R. Hollis ◽  
Hedy L. Kindler ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dose Rate ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Fixed Dose ◽  
Survival Times ◽  
Randomized Phase Ii ◽  
Fixed Dose Rate

PurposeThe relative value of gemcitabine-based combination chemotherapy therapy and prolonged infusions of gemcitabine in patients with advanced pancreatic cancer remains controversial. We explored the efficacy and toxicity of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in a multi-institutional, randomized, phase II study.Patients and MethodsPatients with metastatic pancreatic cancer were randomly assigned to one of the following four regimens: gemcitabine 1,000 mg/m2on days 1, 8, and 15 with cisplatin 50 mg/m2on days 1 and 15 (arm A); gemcitabine 1,500 mg/m2at a rate of 10 mg/m2/min on days 1, 8, and 15 (arm B); gemcitabine 1,000 mg/m2with docetaxel 40 mg/m2on days 1 and 8 (arm C); or gemcitabine 1,000 mg/m2with irinotecan 100 mg/m2on days 1 and 8 (arm D). Patients were observed for response, toxicity, and survival.ResultsTwo hundred fifty-nine patients were enrolled onto the study, of whom 245 were eligible and received treatment. Anticipated rates of myelosuppression, fatigue, and expected regimen-specific toxicities were observed. The overall tumor response rates were 12% to 14%, and the median overall survival times were 6.4 to 7.1 months among the four regimens.ConclusionGemcitabine/cisplatin, fixed dose rate gemcitabine, gemcitabine/docetaxel, and gemcitabine/irinotecan have similar antitumor activity in metastatic pancreatic cancer. In light of recent negative randomized studies directly comparing several of these regimens with standard gemcitabine, none of these approaches can be recommended for routine use in patients with this disease.

Phase II Study of Induction Fixed-Dose Rate Gemcitabine and Bevacizumab Followed by 30 Gy Radiotherapy as Preoperative Treatment for Potentially Resectable Pancreatic Adenocarcinoma

2013 ◽  
Vol 20 (12) ◽  
pp. 3787-3793 ◽  
Author(s):  
George Van Buren ◽  
Ramesh K. Ramanathan ◽  
Alyssa M. Krasinskas ◽  
Ryan P. Smith ◽  
Gerard J. Abood ◽  
...  
Keyword(s):  
Dose Rate ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Fixed Dose ◽  
Preoperative Treatment ◽  
Fixed Dose Rate

A phase II study of fixed-dose rate (FDR) gemcitabine plus cisplatin for metastatic pancreatic adenocarcinoma (PanCa)

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 4107-4107
Author(s):  
A. H. Ko ◽  
E. Dito ◽  
B. Schillinger ◽  
A. P. Venook ◽  
E. K. Bergsland ◽  
...  
Keyword(s):  
Dose Rate ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Fixed Dose ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Fixed Dose Rate

A phase II study of fixed-dose rate (FDR) gemcitabine plus cisplatin for metastatic pancreatic adenocarcinoma (PanCa)

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 4107-4107
Author(s):  
A. H. Ko ◽  
E. Dito ◽  
B. Schillinger ◽  
A. P. Venook ◽  
E. K. Bergsland ◽  
...  
Keyword(s):  
Dose Rate ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Fixed Dose ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Fixed Dose Rate

scholarly journals Phase III Study Comparing Gemcitabine Plus Cetuximab Versus Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma: Southwest Oncology Group–Directed Intergroup Trial S0205

2010 ◽  
Vol 28 (22) ◽  
pp. 3605-3610 ◽  
Author(s):  
Philip A. Philip ◽  
Jacqueline Benedetti ◽  
Christopher L. Corless ◽  
Ralph Wong ◽  
Eileen M. O'Reilly ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Treatment Failure ◽  
Survival Time ◽  
Pancreatic Adenocarcinoma ◽  
Pancreas Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Time To Treatment ◽  
Time To Treatment Failure

Purpose Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. Patients and Methods Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. Results A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset. Conclusion In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.

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