scholarly journals Phase III, Randomized Study of Gemcitabine and Oxaliplatin Versus Gemcitabine (fixed-dose rate infusion) Compared With Gemcitabine (30-minute infusion) in Patients With Pancreatic Carcinoma E6201: A Trial of the Eastern Cooperative Oncology Group

2009 ◽  
Vol 27 (23) ◽  
pp. 3778-3785 ◽  
Author(s):  
Elizabeth Poplin ◽  
Yang Feng ◽  
Jordan Berlin ◽  
Mace L. Rothenberg ◽  
Howard Hochster ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dose Rate ◽  
Median Survival ◽  
Single Agent ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Fixed Dose ◽  
Fixed Dose Rate

PurposeSingle-agent gemcitabine (GEM) is standard treatment of metastatic pancreatic cancer. Fixed-dose rate (FDR) GEM and GEM plus oxaliplatin have shown promise in early clinical trials. E6201 was designed to compare overall survival (OS) of standard weekly GEM 1,000 mg/m2/30 minutes versus GEM FDR 1,500 mg/m2/150 minutes or GEM 1,000 mg/m2/100 minutes/day 1 plus oxaliplatin 100 mg/m2/day 2 every 14 days (GEMOX).MethodsThis trial included patients with metastatic or locally advanced pancreatic cancer, normal organ function, and performance status of 0 to 2. The study was designed to detect a 33% difference in median survival (hazard ratio [HR] ≤ 0.75 for either of the experimental arms) with 81% power while maintaining a significance level of 2.5% in a two-sided test for each of the two primary comparisons.ResultsEight hundred thirty-two patients were enrolled. The median survival and 1-year survival were 4.9 months (95% CI, 4.5 to 5.6) and 16% for GEM, 6.2 months (95% CI, 5.4 to 6.9), and 21% for GEM FDR (HR, 0.83; stratified log-rank P = .04), and 5.7 months (95% CI, 4.9 to 6.5) and 21% for GEMOX (HR, 0.88; stratified log-rank P = .22). Neither of these differences met the prespecified criteria for significance. Survival was 9.2 months for patients with locally advanced disease, and 5.4 months for those with metastatic disease. Grade 3/4 neutropenia and thrombocytopenia were greatest with GEM FDR. GEMOX caused higher rates of nausea, vomiting, and neuropathy.ConclusionNeither GEM FDR nor GEMOX resulted in substantially improved survival or symptom benefit over standard GEM in patients with advanced pancreatic cancer.

Phase III trial of gemcitabine (30-minute infusion) versus gemcitabine (fixed-dose-rate infusion [FDR]) versus gemcitabine + oxaliplatin (GEMOX) in patients with advanced pancreatic cancer (E6201)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA4004-LBA4004 ◽  
Author(s):  
E. Poplin ◽  
D. E. Levy ◽  
J. Berlin ◽  
M. L. Rothenberg ◽  
P. J. O’Dwyer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Fixed Dose ◽  
Response Patterns ◽  
Significance Level

LBA4004 Background: Gemcitabine (GEM) is the cornerstone of treatment of metastatic pancreatic cancer (PANCA). FDR GEM or GEMOX are promising, but have yet to convincingly demonstrate a survival advantage over GEM alone. E6201 compares overall survival (OS) of standard GEM 1000 mg/m2/30 min wkly ×7 over 56 days then wkly ×3 q28 d (ARM A) vs. FDR GEM 1500 mg/m2/150 min wkly ×3 q28 days (ARM B) or GEM 1000 mg/m2/100-min/d1 + oxaliplatin 100 mg/m2/d2 q14d (ARM C). Secondary endpoints are the comparison of the experimental regimens, toxicity, response, patterns of failure, progression-free survival and quality-of-life. Methods: This multi-institutional trial included patients (pts) with measurable and non-measurable advanced, unresectable PAN CA, normal organ function and PS 0–2. Pts were chemonaive, although prior adjuvant radiosensitizing 5FU was permitted. Pts were stratified by PS 0–1 vs 2 and locally advanced vs metastatic disease The study was designed to detect a 33% difference in median survival (hazard ratio 1.33) with 81% power while maintaining a significance level of 2.5% in a two-sided test for each of the two primary comparisons, assuming exponential failure and median survival of 6 mo for Arm A and 8 mo for Arm B and C (N = 750 eligible). Results: Accrual started in 3/03 and completed in 3/05. Median follow up is 5.8 mo. 833 pts (53% men; 88% PS 0–1; 88% metastatic), were randomized with 280, 277 and 276 pts in Arms A, B and C. The third interim analysis was conducted with 89.5% information on 3/2006. The predominant toxicity, available for 758 pts, was grade 3/4 myelosuppression and fatigue. Two deaths from ARDS and infection occurred. Median OS for ARMS A, B, and C are 4.96, 6.01 and 6.47 months, respectively. Hazard ratio A vs B is 1.21 with stratified log rank of 0.053 and for A vs C is 1.22 with stratified log rank of 0.045, neither statistically significant. Conclusion: E6201 final OS results will be available in June, 2006. [Table: see text] [Table: see text]

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 capecitabine and gemcitabine fixed dose rate (FDR) in patients with advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15530-e15530
Author(s):  
G. Tonini ◽  
B. Vincenzi ◽  
E. Vasile ◽  
V. Catalano ◽  
V. Virzì ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dose Rate ◽  
Phase Ii ◽  
Advanced Pancreatic Cancer ◽  
New Combination ◽  
Fixed Dose ◽  
Tumour Control ◽  
Intention To Treat ◽  
Fixed Dose Rate ◽  
Ecog Ps

e15530 Background: The aims of this phase II trial are to determine the activity and the safety of the new combination modality with Gemcitabine fixed dose rate (FDR) infusion and Capecitabine in patients with advanced pancreatic cancer. Methods: Patients with unresectable pancreatic cancer who had pathologically confirmed adenocarcinoma, no prior chemotherapy, ECOG PS < 2 and measurable disease were enrolled. Gemcitabine (800 mg/mq IV infused in 80 minutes on days 1 and 8) and Capecitabine (650 mg/mq orally twice daily for 14 days) were administered and repeated every 21 days. Results: 47 patients were enrolled between January 2004 and October 2008. Median age was 66 (range: 37–79), 18 female and 29 male. A total of 299 cycles were administered, median cycles for patient were 6 (range: 1–17). CR was observed in one patient (2.1 %) and 10 patients achieved PR (21.3 %) giving an overall response rate of 23.4 % in intention-to-treat population. 22 pts (46.8 %) had stable disease obtaining an overall tumour control of 70.2 %. The median time to progression was 5.2 months (95 % CI, 2.4–7.6); the median overall survival was 8.4 months (95 % CI, 5.5–20). Grade 3–4 neutropenia was observed in 29.8 % of subjects, thrombocytopenia in 6.4 %. Grade 1–2 non-hematological toxicities were asthenia (61.7 %), diarrhea (29.8%), stomatitis (29.8 %) and hand foot syndrome (2.1 %). There were no treatment-related deaths. Gemcitabine was skipped at least once/reduced in 51/10.6 % of the patients, respectively. Capecitabine was skipped at least once/reduced in 16/8 % of the patients, respectively. Conclusions: The combination of FDR Gemcitabine and Capecitabine with this modality of infusion is feaseble, safe and seems to be active. No significant financial relationships to disclose.

Randomized Phase III Study of Exatecan and Gemcitabine Compared With Gemcitabine Alone in Untreated Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (27) ◽  
pp. 4441-4447 ◽  
Author(s):  
Ghassan K. Abou-Alfa ◽  
Richard Letourneau ◽  
Graydon Harker ◽  
Manuel Modiano ◽  
Herbert Hurwitz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Water Soluble ◽  
Phase Iii ◽  
Eligibility Criteria

Purpose Exatecan mesylate is a hexacyclic, water-soluble, topoisomerase-1 inhibitor. Exatecan has single-agent and combination activity with gemcitabine in advanced pancreatic cancer. A multicenter, randomized, phase III trial comparing exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer was conducted. Patients and Methods Eligibility criteria included Karnofsky performance status ≥ 60%, locally advanced or metastatic pancreatic adenocarcinoma, and no prior chemotherapy. Radiation alone for locally advanced disease was permitted. Patients were randomly assigned on a 1:1 basis. For the exatecan plus gemcitabine arm, exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2 were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3 weeks of a 4-week cycle. Tumor assessment was performed every 6 weeks. The primary end point was overall survival. An intent-to-treat analysis was used. Results From August 2001 to January 2003, 349 patients were randomly assigned, 175 to exatecan plus gemcitabine and 174 to gemcitabine alone. Twenty-four patients (6.9%) were not treated. The median survival time was 6.7 months for exatecan plus gemcitabine and 6.2 months for gemcitabine alone (P = .52). One complete response (CR; < 1%) and 11 partial responses (PRs; 6.3%) were observed in the exatecan plus gemcitabine treatment group, and one CR (< 1%) and eight PRs (4.6%) were observed in the gemcitabine-alone group. Grade 3 and 4 toxicities were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone arm; neutropenia (30% v 15%) and thrombocytopenia (15% v 4%). Conclusion Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to overall survival in the first-line treatment of advanced pancreatic cancer.

Gemcitabine (G) fixed-dose-rate infusion (FDR) plus erlotinib (E) in patients with advanced pancreatic cancer (APC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 304-304 ◽  
Author(s):  
A. Munoz Llarena ◽  
J. Mane ◽  
G. Lopez-Vivanco ◽  
A. Ruiz de Lobera ◽  
A. Sancho ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Dose Intensity ◽  
Phase Iii ◽  
Fixed Dose ◽  
Hematologic Toxicity ◽  
Fixed Dose Rate ◽  
Recent Phase ◽  
Fixed Dose Rate Infusion ◽  
Ecog Ps

304 Background: G (30-minute infusion) plus E improves survival in patients with APC compared with G alone. In a recent phase III trial, G-FDR showed a trend to better OS compared with standard G (6.2 vs. 4.9 months, HR 0.83, p=0.04), although the study was underpowered to detect great difference in OS. Based on our previous experience with G-FDR, we decided to evaluate the combination of G-FDR plus E, after E approval for APC. Methods: Patients with previously untreated pathologically confirmed APC, locally advanced (LAPC) or metastatic (MPC), and ECOG PS 0-2 were included. G 1500 mg/m2 was given by 150-min infusion (10 mg/m2/min) on days 1, 8, and 15 every 28 days combined with E 100 mg/day orally. Treatment modifications for G-FDR were planned according with previously Tempero's phase II trial, and as described in prescribing information for E. Results: 62 pts were included (36M/26F), with a median age of 63 y-o (range 37-78). ECOG PS 0/1/2: 19/40/3. LAPC/MPC: 16/46. All except one had measurable disease. ORR was 13% (8 PR), 95% CI: 4.7-21.3, and there were 34 (55%) SD. Mean relative dose intensity for G was 0.76 and 0.90 for E. Main hematologic toxicities 3/4 per pt: anaemia 12/0, thrombocytopenia 7/4, neutropenia 18/7. Acneiform rash 1/2/3 occurred in 16/16/3 pts. Other relevant adverse events were (grade 2/3/4): diarrhoea 18/3/0, mucositis 5/1/0, infection 9/8/1, thrombosis 1/4/1 and vomiting 6/4/0. There were three treatment-related deaths (septic shock, cholangitis, and bilateral pulmonary embolism). Ten pts (all LAPC) received RT after ≤ 6 cycles, all with concomitant capecitabine 825 mg/m2 bid. In 4 pts salvage surgery were performed: 2 R0, 1 R1 and 1 R2. Median PFS was 4.9 months (95% CI: 3-6.7), 7.9 m for LAPC and 2.5 m for MPC (p = 0.004). Median OS was 10 months (95% CI: 7.1-12.9), 17.5 m for LAPC and 7 m for MPC (p = 0.019). OS was significantly shorter in males (p = 0.01) and in pts taking major opioids (p = 0.027). There was a trend to better OS in pts who developed skin rash grade ≥ 2 (p = 0.078). Conclusions: In this noncomparative study, G-FDR plus E is a feasible regimen in APC with an acceptable toxicity and notable activity. G-FDR seems to increase hematologic toxicity compared with standard infusion. No significant financial relationships to disclose.

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