RP101 improves the efficacy of gemcitabine in treating pancreatic carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14075-14075
Author(s):  
M. Haenel ◽  
D. Quietzsch ◽  
V. Heinemann ◽  
S. Boeck ◽  
R. M. Schmid ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase 1 ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Underlying Disease ◽  
Fixed Dose ◽  
Survival Status ◽  
Phase 2 Study ◽  
One Year

14075 Background: (E)-5-(2-bromovinyl)-2’-deoxyuridine (BVDU, RP101), was initially tested in a phase 1 pilot study in pancreatic cancer. Patients (n=13) received gemcitabine (1000 mg/m2), cisplatin (50 mg/m2) and RP101 (500 mg/day). The median survival was 447 days and the TTP was 280 days. Ten of the 13 pts lived longer than one year, 4 nearly two years. Based on these promising results a phase 2 study was initiated to explore varying doses of RP101 used with a fixed dose of GEM. Methods: Pts with advanced pancreatic adenocarcinoma were eligible for treatment in this single arm study. 22 pts (16 stage IV and 5 stage III) received GEM 1000 mg/m2 on days 1, 8 and 15 of a 28-day schedule. RP101 treatment, at doses of 500, 625, 750, 875 or 1000 mg/day, was on the same day and for three days after chemotherapy. The mean age was 60 years and 73% of pts were males. Results: The results are based on interim data from an ongoing study and patients at the 2 highest dose groups are still being treated. All RP101 dose groups were combined for analyses, which included all enrolled pts. The data on the 6-month survival status show that 41% are alive; 23% dead; and 36% followed less than 6 months. The median survival (95% CI) is 7.1 months (5.9, not calculated) and 14/22 pts (64%) are still alive. The 6 month survival rate (95% CI) is 0.69 (0.52, 0.85). This compares very favorably with a large recent randomized trial in which pts who received GEM alone had a median survival (95%CI) of 5.9 months (5.1–6.7). PFS and TTP continue to be assessed in this ongoing trial. There appears to be a dose dependent increase in peak GEM levels as a function of the dose of RP101. To date, adverse events are consistent with those observed with GEM or the underlying disease. Conclusion: RP101 may improve treatment of advanced pancreatic cancer when used with gemcitabine. Updated data on survival, PFS, and safety will be presented based on available data. [Table: see text]

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 2207

2017 ◽  
Vol 1 (S1) ◽  
pp. 32-33
Author(s):  
Jacob Ezra Shabason ◽  
Jerry Chen ◽  
Smith Apisarnthanarax ◽  
Nevena Damjanov ◽  
Bruce Giantonio ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase 1 ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Fractionated Radiotherapy ◽  
Grade 3

OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.

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.

Neoadjuvant therapy with nanoparticle albumin-bound (nab)-paclitaxel to enhance the resectability of locally advanced pancreatic cancer (LAPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14644-e14644
Author(s):  
Prasad Cooray ◽  
Andrew Peter Dean
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Surgical Resection ◽  
Median Survival ◽  
Adjuvant Treatment ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Cancer Recurrence ◽  
Stage Iv ◽  
Borderline Resectable

e14644 Background: Resection offers the only probability of cure for pancreatic adenocarcinoma but only a minority have resectable disease at diagnosis. Effective neo-adjuvant therapy for LAPC could down-size the tumor rendering it resectable. Neo-adjuvant therapy may retard cancer dissemination thought to occur early in pancreatic cancer. The aim of this study was to retrospectively evaluate if neo-adjuvant treatment with nab-paclitaxel in patients with LAPC could result in tumor down-sizing to allow resection and improve outcomes. Methods: Data was collected from the medical records of pancreatic cancer patients who presented to two clinics from 06/2009 to 12/2011 and were treated with nab-paclitaxel (n = 63). Resectability was assessed by review of imaging by the radiologist and the treating surgeon. Twenty three of 63 patients had LAPC and 40/63 had stage IV disease. Of the LAPC patients, 8/23 (35%) were classified as borderline resectable (BR) and 15/23 (65%) were classified as unresectable (UR). Patients received nab-paclitaxel (100-125 mg/m2 D1,8,15) in combination with gemcitabine or carboplatin. The BR/UR patients (n=23) received a median 5 cycles of chemotherapy. They were re-evaluated for suitability for surgical resection. Results: Following neo-adjuvant treatment, 16/23 (69%) had a radiological PR and 17/23 (74%) had a major biochemical response (defined as >70% decline in Ca19.9 level). A total of 6/23 patients (26%) were then able to undergo surgical resection, with resections planned for further 2/23 (8%) patients.Of the 6 resected patients, 4 had R0 resections and 2 had R1 resection. After a median follow up of 18 months, all 6 resected patients are alive and 4 of them remain free of cancer recurrence. The median survival for patients who remained unresectable (15/23) was 9 months. The median survival for converted patients (6/23) has not yet reached. Conclusions: These results suggest that a subgroup of patients with LAPC could be converted to a resectable stage with the use of nab-paclitaxel as neo-adjuvant therapy. Such converted patients may enjoy durable improved outcomes and this approach warrants further investigation in a phase II clinical trial.

Final results of a phase Ib study of gemcitabine plus PEGPH20 in patients with stage IV previously untreated pancreatic cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 359-359 ◽  
Author(s):  
Sunil R. Hingorani ◽  
William Proctor Harris ◽  
Joseph Thaddeus Beck ◽  
Boris A. Berdov ◽  
Stephanie Ann Wagner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase 1 ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Tumor Stroma ◽  
Clinical Activity ◽  
Phase 2 ◽  
Chemotherapy Drugs ◽  
Metastatic Sites

359 Background: Poor outcome in pancreatic cancer (PDA) has been associated with tumor stroma limiting access of chemotherapy drugs. PEGPH20 (PEG), PEGylated recombinant human hyaluronidase, which depletes hyaluronan (HA) in tumors, has demonstrated anti-tumor activity in preclinical PDA models. In a KPC model of PDA, PEG + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Phase 1 PEG monotherapy studies, the MTD was 3µg/kg. The most common adverse events (AEs) were musculoskeletal events. Methods: This was a phase 1b study to determine the recommended phase 2 dose of PEG + Gem in patients (pts) with previously untreated Stage IV pancreatic cancer. PEG was given at 1, 1.6, or 3µg/kg IV twice weekly Wks 1–4 and weekly Wks 5–7, followed by 1 wk rest. Gem was given at 1000mg/m2IV once weekly for Wks 1–7, then 1 wk rest. Thereafter, PEG + Gem were given once weekly for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEG doses. Due to evolving SOC, the study was discontinued before initiation of the phase 2 randomization. Results: Twenty-eight pts were enrolled in the study. The majority of the patients (89%) had metastatic sites in the liver. Four, 4 and 20 pts received PEG at 1, 1.6 and 3µg/kg, respectively. The most common AEs related to PEG were muscle spasm (54%), myalgia (39%), arthralgia (29%), peripheral edema (29%), fatigue (25%), and extremity pain (18%). Median progression free survival (PFS) and overall survival (OS) were assessed and were 154 and 200 days, respectively. In an exploratory analysis, tumor biopsies from 17 pts were evaluated for HA levels (HAhigh or HAlow). 6 pts were determined to have HAhigh tumors and 11 pts had HAlow tumors. The median PFS and OS for HAhigh pts were 219 days (95% CI: 159-276) and 395 days (95% CI: 210-578). For HAlowpts median PFS and OS were 108 (95% CI: 14-163) and 174 days (95% CI: 34-293). Conclusions: PEG + Gem is generally well tolerated in advanced pancreatic cancer and shows promising clinical activity, especially in pts with HAhigh tumors. ClinicalTrials.gov Identifier: NCT01453153.

scholarly journals Higher overall survival in metastatic pancreatic cancer: the impact of where and how treatment is delivered

2015 ◽  
Vol 13 (3) ◽  
pp. 347-351 ◽  
Author(s):  
Pedro Luiz Serrano Usón Junior ◽  
Monique Sedlmaier França ◽  
Heloisa Veasey Rodrigues ◽  
Antônio Luiz de Vasconcellos Macedo ◽  
Alberto Goldenberg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Survival ◽  
Metastatic Cancer ◽  
Treatment Options ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Tumor Location ◽  
Access To Treatment ◽  
The Impact

Objective To determine the overall survival of patients with advanced pancreatic cancer and evaluate factors that impact prognosis in a private cancer center.Methods Data from the Hospital Cancer Registry at Hospital Israelita Albert Einstein were retrospectively collected. The patients enrolled had metastatic cancer at diagnosis or earlier staging and subsequent recurrence. Cases of neuroendocrine tumors were excluded.Results A total of 65 patients were evaluated, including 63 with adenocarcinoma. The median overall survival for patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV cancer, there was no evidence of a statistically significant association between median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age (p=0.152). However, the number of lines of chemotherapy was significantly associated with survival (log-rank p=0.013), with an estimated median survival of 10.2 months for patients who received up to two lines of treatment and 23.5 months for those receiving more than two lines of chemotherapy.Conclusion The survival of patients treated was longer than that reported in the literature. The only statistically significant factor related to increased survival was higher number of lines of chemotherapy received. We believe that the higher socioeconomic status of patients surveyed in this study, as well as their greater access to treatment options, may have influenced their overall survival.

Analysis of statistical indicators of the population of Saint Petersburg with malignant neoplasms of pancreas

2021 ◽  
Vol 23 (2) ◽  
pp. 155-164
Author(s):  
Vladislav E. Moiseenko ◽  
Alexander V. Pavlovsky ◽  
Dmitry A. Granov ◽  
Larisa V. Kochorova ◽  
Inna V. Dodonova ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stage Iv ◽  
Malignant Neoplasms ◽  
Number Of Patients ◽  
Incidence And Mortality ◽  
Significant Downward Trend ◽  
Accumulation Index ◽  
One Year ◽  
The One ◽  
Statistical Indicators

Morbidity and mortality from pancreatic cancer is an urgent medical and social problem. Evaluation of statistical indicators in dynamics makes it possible to identify organizational and clinical problems in providing care to patients with malignant neoplasms of the pancreas. Medical and statistical indicators of incidence of malignant pancreatic neoplasms in St. Petersburg residents are evaluated. The assessment of medical and statistical indicators of the incidence of malignant neoplasms of the pancreas in residents of St. Petersburg. Statistical data were studied for the period from 2014 to 2019. The increase in the "rough" indicator of primary morbidity changed from 417.99 per 100 thousand population in 2014 to 505.6 in 2019. In the structure of primary cancer incidence, the indicator of active detection of pancreatic cancer glands in 2014 amounted to 3.6%, in 2019 3.8%. The proportion of patients with diagnoses confirmed morphologically increased from 48.9% to 61.4%. The proportion of patients with newly diagnosed stage IV of the disease changed from 39.5% in 2014 to 51.4% in 2019, and in patients with stage III in 2019 it was 33.3% (a decrease in comparison with 2014 15.3%). In 2019, the disease was diagnosed at stage II in 15.2% of patients. The proportion of patients with stage I in 2019 was 6.6%, this indicator in 2014 was registered at the level of 19.2%. From 2014 to 2019, the one-year mortality rate did not change and amounted to 67.9 and 67.4%, respectively (the decrease was 0.7%). Over the past 5 years, there has been no significant downward trend in the "rough" incidence and mortality rates from pancreatic cancer. However, in the dynamics, there was an increase in the number of patients registered for 5 or more years, and an increase in the accumulation index of the contingent of patients with pancreatic cancer.

scholarly journals NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Patrick J. Mansky ◽  
Dawn B. Wallerstedt ◽  
Timothy S. Sannes ◽  
Jamie Stagl ◽  
Laura Lee Johnson ◽  
...  
Keyword(s):  
Clinical Response ◽  
Phase 1 ◽  
Plasma Concentrations ◽  
Stage Iv ◽  
Dosage Level ◽  
Maximum Tolerated Dose ◽  
Stage I ◽  
Fixed Dose ◽  
Mistletoe Lectin ◽  
Mistletoe Extract

Purpose.European Mistletoe (Viscum albumL.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM.Methods.Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery.Results.DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high.Conclusion.GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

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