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.

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.

A phase III trial of virulizin plus gemcitabine vs. gemcitabine alone in advanced pancreatic cancer: Results of subgroup analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4116-4116 ◽  
Author(s):  
J. A. Wright ◽  
J. Osterlee ◽  
S. Fekete ◽  
Y. Lee ◽  
A. H. Young
Keyword(s):  
Pancreatic Cancer ◽  
Metastatic Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Double Blind ◽  
Significant Difference ◽  
Ecog Ps ◽  
To Receive

4116 Background: Virulizin (V) is a novel antitumor immune modulator that improves survival in pancreatic cancer patients (pts) as monotherapy. A double-blind, multicenter, randomized, phase III study was conducted to evaluate the survival benefits and safety of V in combination with gemcitabine (G) in pts with advanced pancreatic cancer. Methods: Chemo-naive pts with locally advanced or metastatic pancreatic cancer with ECOG Performance Status (PS) of 0, 1 or 2 were enrolled. Pts were randomized to receive intramuscular injections of either V or placebo (P) 3 times weekly + G (1,000 mg/m2 weekly ×7 with 1 week rest, then weekly ×3 q4w). Randomization was stratified according to ECOG PS (0 or 1, and 2) and extent of disease (locally advanced and metastatic). Pts who showed no clinical benefit or were intolerant to G entered 2nd-line therapy (stage 3), in which pts continued to receive either V or P alone or with 5-FU, or best supportive care. The primary endpoint was survival, defined as time from baseline/treatment day 1 to time of death from any cause. Results: The intent to treat (ITT) population comprised 434 pts, of which 377 were efficacy evaluable (EE). Median overall survival for V + G was 6.3 months for the ITT population (6.8 months for EE pts) and 6 months for P + G for both ITT and EE pts. While differences in survival times were not statistically significant, exploratory analysis showed encouraging results in specific subgroups treated with V + G ( table ). Importantly, a significant difference was found in stage 3 pts who received V in a salvage setting compared to pts who received P. Conclusions: Pancreatic cancer pts with either low ECOG PS or metastatic cancer showed a survival benefit when treated with V + G, which was significant in pts who continued to receive V as a salvage therapy. Further studies in these targeted patient populations are being considered. [Table: see text] No significant financial relationships to disclose.

Phase II study of a fixed dose-rate infusion of gemcitabine associated with erlotinib in advanced pancreatic carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15013-15013
Author(s):  
E. Espinosa ◽  
J. Feliu ◽  
J. de Castro ◽  
C. Belda ◽  
E. Casado ◽  
...  
Keyword(s):  
Pancreatic Carcinoma ◽  
Dose Rate ◽  
Locally Advanced ◽  
Fixed Dose ◽  
Low Grade ◽  
Fixed Dose Rate ◽  
Fixed Dose Rate Infusion ◽  
Advanced Pancreatic Carcinoma ◽  
Grade 3 ◽  
Rate Infusion

15013 Background: The efficacy of gemcitabine in pancreatic cancer can be improved by its combination with erlotinib. Likewise, a fixed dose-rate infusion of gemcitabine seems to be superior to the conventional 30-minute infusion. Our objective was to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with erlotinib in patients with advanced adenocarcinoma of the pancreas. Methods: From May 2005 to October 2006, 21 chemotherapy-naïve patients were included, median age 62 years (range 47 - 78), male/female 12/9. Five patients (24%) had locally advanced disease and 16 (76%) distant metastases. The Karnofsky score was 80–100 in 11 (52%), and 60–70 in 10 (48%). Treatment consisted of gemcitabine 1200 mg/m2 given as a 120-minute infusion on days 1, 8, 15, plus erlotinib 100 mg p.o daily. Cycles were repeated every 4 weeks. Results: A total of 80 cycles of chemotherapy were delivered with a median of 3.8 per patient (range 1- 8). There were five partial responses (24%, 95% CI: 8.4 - 47.6%), whereas seven patients had stable disease (33%) and 9 had a progression (43%). The median time to progression was 4 months. After a median follow-up of 6 months (1–14 months), the median overall survival has not been achieved. Toxicity was low. Grade 3- 4 WHO toxicities per patient were as follows: neutropenia in 5 (24%), thrombocytopenia in 1 (5%) and anaemia in 3 (14%). Grade 1–2 rash appeared in 8 (38%) and grade 3 in 3 (14%). Four patients (19%) had diarrhoea grade 1–2. Conclusions: These preliminary results suggest that a fixed dose-rate infusion of gemcitabine associated with erlotinib is active and well tolerated in patients with advanced pancreatic carcinoma. No significant financial relationships to disclose.

Phase II study of induction chemotherapy with fixed dose rate (FDR) gemcitabine and cisplatin followed by concurrent chemoradiation with capecitabine for locally advanced pancreatic cancer (LAPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15122-15122
Author(s):  
J. Kim ◽  
S. Im ◽  
H. Park ◽  
E. Chie ◽  
J. Hwang ◽  
...  
Keyword(s):  
Partial Response ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Additional Patient ◽  
Fixed Dose ◽  
Ecog Ps ◽  
Grade Iii

15122 Background: Despite the use of 5-FU based chemoradiotherapy (CRT) over the past decades, prognosis of patients with LAPC remains dismal. To deliver more efficient systemic treatment earlier and reduce toxicity of CRT, we designed a treatment protocol consisting of induction (IND) chemotherapy with FDR gemcitabine (GEM) and cisplatin (CDDP), followed by CRT with capecitabine (CAP) in LAPC. Methods: Eligible patients had unresectable, histologically confirmed adenocarcinoma of pancreas, ECOG PS of 0–2, and no prior chemo- or radiotherapy for this phase II study. Patients received FDR GEM 1000 mg/m2 (D1,8) and CDDP 60 mg/m2 (D1) every 3 weeks for 3 cycles. Patients without disease progression subsequently received CRT of 55.8 Gy in 31 fractions concurrently with CAP, 650 mg/m2 given twice daily without drug holidays. Four weeks after CRT, FDR GEM 1000 mg/m2 was given on day 1, 8 every 3 weeks for 3 cycles. Time to progression was the primary endpoint. Results: Between Jan 2005 and Nov 2006, 21 patients were enrolled (median age 59, M/F: 13/8, ECOG PS 0/1: 3/18). Two patients withdrew consent after 1st and 2nd cycle and remaining 19 patients completed all three cycles of IND chemotherapy, with three (15.8%) out of 19 evaluable patients achieving partial response (0 CR, 3 PR, 14 SD, 2 PD). All 17 patients completed CRT with mean radiation dose of 55.4 Gy. Further four patients progressed during CRT, while one additional patient achieved partial response. As of Jan 2007, 5 patients died and 12 patients showed tumor progression. Median TTP was 12.5 mo (95% CI: 4.2–20.8) and median survival was not reached with median follow up duration of 9.7 months. Grade III/IV toxicities included neutropenia (38.1%/9.5%), thrombocytopenia (4.8%/0%), and anemia (14.3%/0%) during IND phase. Toxicites were generally mild during CRT phase with grade III neutropenia and diarrhea occurring in one and two patients, respectively. One patient died of neutropenic sepsis after 3rd cycle of IND chemotherapy. Conclusions: FDR GEM-CDDP induction chemotherapy followed by CAP-RT and maintenance FDR GEM is feasible and active with promising TTP of 12.5 months. Enrollment continues till reaching target accrual of 37 patients. No significant financial relationships to disclose.

Randomized phase III Trial of MEDI4736 (durvalumab) as concurrent and consolidative therapy or consolidative therapy alone for unresectable stage 3 NSCLC: A trial of the ECOG-ACRIN Cancer Research Group (EA5181).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8584-TPS8584
Author(s):  
John M. Varlotto ◽  
Zhuoxin Sun ◽  
Suresh S. Ramalingam ◽  
Heather A. Wakelee ◽  
Christine M. Lovly ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Concurrent Chemotherapy ◽  
Phase Iii ◽  
Fixed Dose ◽  
Hematologic Toxicity ◽  
Eligibility Criteria ◽  
Unresectable Stage ◽  
One Year

TPS8584 Background: Platinum-based concurrent chemoradiation(CRT) followed by one year of the human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, durvalumab, which blocks the interaction of PD-L1 with its receptors PD-1 and CD80, is the standard of care for locally advanced, unresectable non-small cell lung cancer (NSCLC). Early studies have noted the feasibility of concomitant administration of radiotherapy and immune checkpoint inhibition in NSCLC. EA5181 will evaluate the use of concomitant durvalumab with chemo-radiotherapy for locally advanced NSCLC. Methods: EA5181 is a randomized, multi-center, phase III study for patients with unresectable Stage III NSCLC comparing the efficacy of CRT with concomitant durvalumab to CRT, followed by one year of durvalumab. Eligibility criteria include: an ECOG PS of 0-1, adequate pulmonary function (FEV1 and DLCO both > 40%), no history of auto-immune disease and no past chemotherapy or RT for this lung cancer. Stratification factors include age, sex, stage, and planned concurrent chemotherapy type. Eligible patients with be randomized 1:1 to receive 60Gy RT (2Gy fractions) CRT and durvalumab (Arm A) or 60Gy CRT (Arm B). Investigators will be allowed to choose from three different chemotherapy options: cisplatin/etoposide q 28 days, Pemetrexed/cisplatin q 21 days, and weekly paclitaxel/Carboplatin. Arm A will use 750mg fixed of durvalumab (considered equivalent to 10mg/kg) on days 1, 11, and 21 of RT. Assuming no disease progression, patients in both arms will be followed by monthly (q28 days) fixed dose of 1500mg durvalumab for one year which will be given optimally within 14 days of radiation or when (non)hematologic toxicity is < Grade 2. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, incidence of local/distant progression and toxicity. The target sample size is 660 patients, anticipated to recruit over 55 months, with follow up for an additional 42 months. This provides approximately 82% power if the true hazard ratio for overall survival was 0.75 or less, with 2-sided alpha of 0.05, and assuming a median survival of 42.5 months in the control arm. The study was activated on 04/09/20 and has currently accrued 90 patients on 02/03/21. Clinical trial information: NCT04092283.

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]

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.

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