Patient reported abdominal pain as a surrogate of the clinical benefit of tipifarnib in pancreatic cancer patients.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 275-275
Author(s):  
Antonio Gualberto ◽  
Catherine Rose Scholz ◽  
Eric Van Cutsem
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Abdominal Pain ◽  
Cancer Patients ◽  
Clinical Benefit ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Study Entry ◽  
Primary Study ◽  
Patient Reported

275 Background: Tumor CXCL12 expression identifies patients who may benefit from tipifarnib therapy. In pancreatic cancer, CXCL12 is known to decrease abdominal pain by inducing the migration of pain suppressing Schwann cells to tumor lesions. Given the association between CXCL12 and pain suppression, we investigated whether the absence of patient reported abdominal pain could be a surrogate of clinical benefit from tipifarnib in pancreatic cancer patients. Methods: We conducted a retrospective analysis of a randomized placebo-controlled trial comparing gemcitabine plus tipifarnib (GT) versus gemcitabine plus placebo (GP) in pancreatic adenocarcinoma patients. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine at standard dosing. Primary study end point was overall survival. Results: 688 patients were enrolled of whom 155 (22.5%) reported no abdominal pain at study entry, 81 received GT and 74 GP. Baseline characteristics were balanced in the subset of patients with no reported abdominal pain (GT,GP): median age (63,59), female gender (35%,43%), ECOG 0-1 (89%,90%), metastatic disease (64%,70%), 6-month weight loss >10% (48%,39%), 6-month jaundice history (51%,45%), and prior Whipple surgery (16%,13%). Subjects receiving GT who did not report abdominal pain at study entry had higher frequency of locally advanced disease (36% vs 24%) and 6-month jaundice (51% vs 38%), and lower frequency of lung (6% vs 14%) and peritoneum (4% vs 13%) metastases than those reporting pain. No differences in survival were observed in the overall study. Median overall survival for GT was 193 vs 182 days for GP. Notably, absence of abdominal pain at study entry was associated with higher median survival in the GT arm (no pain, pain): 305 vs 176 days, HR=0.52, p<0.0001, whereas no significant effect was observed in the control arm: 184 vs 182 days. A trend for better survival with GT was observed in subset of patients with no abdominal pain at study entry (GT,GP): 305 vs 184 days, p=0.058. Conclusions: Absence of abdominal pain may serve as a surrogate of clinical benefit from tipifarnib in pancreatic cancer. (Van Cutsem et al. JCO 2004;22:1430-8; NCT00005648; Trial Sponsor: J&J PRD). Clinical trial information: NCT00005648.

Modified IPCW model: A method for adjusting for bias in the estimation of overall survival due to the use of second and third line therapies in locally advanced or metastatic pancreatic cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15787-e15787
Author(s):  
N. E. Iznaga Escobar ◽  
Patricia Lorenzo Luaces ◽  
Lizet Sanchez Valdes ◽  
Carmen Valenzuela Silva ◽  
Tania Crombet Ramos ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Cox Regression ◽  
Locally Advanced ◽  
Secondary Analysis ◽  
Metastatic Pancreatic Cancer ◽  
Fixed Dose ◽  
Line Treatment ◽  
Newly Diagnosed

e15787 Background: Nimotuzumab, a unique and affinity differentiated anti-EGFR antibody had been used in combination with gemcitabine on the treatment of pancreatic cancer patients. The aim of the study was to evaluate overall survival. Methods: Patients with newly diagnosed, locally advanced or metastatic pancreatic cancer, KPS ≥ 70 %, 18-72 years old, with adequate renal and liver function were included. Pts received gemcitabine 1000 mg/m2and nimotuzumab or placebo fixed dose of 400 mg once a wk, for 3 wks, followed by a 1-wk rest (d1, 8, 15, q28) until disease progression or unacceptable toxicity. The primary endpoint was OS and secondary PFS, ORR, CBR, safety and QoL. For OS determination, a KM log-rank test was used and a modified IPCW with a cox regression as a secondary analysis. On this evaluation using a modified IPCW model, 41.7% of pts from treatment arm and 42.7% from control arm who received 2nd and 3rd line treatment were censored after progression, while pts that did not receive 2nd and 3rd line treatment were weighted to compensate for the bias created by censoring switchers to 2nd and 3rd line treatment. Results: 192 pancreatic cancer pts were recruited. Ninety-six pts (62 male and 34 female) with a median age of 67 years, range (31, 83) were randomized to treatment arm and 96 pts (57 male and 39 female) with a median age of 64 years, range (41, 82) were randomized to control arm. In the primary analysis, median OS [95% CI] in the treatment arm was 8.57 mo [5.93, 10.90] vs 6.03 mo [4.97, 7.60] in the control arm. The HR [95% CI], 0.83 [0.62, 1.12] and p = 0.23 and when a modified IPCW model as a secondary analysis was used to remove the effect of 2nd and 3rd line therapies, the median OS was statistically significant with a HR [95% CI], 0.81 [0.67, 0.98] and a p = 0.030. The median PFS [95% CI] was 4.43 mo [3.67, 6.00] in the treatment arm vs 3.47 mo [2.60, 4.03] in the control arm with a HR [95% CI] 0.68 [0.51, 0.92] and p = 0.012. Conclusions: A modified IPCW model had proven that addition of nimotuzumab to gemcitabine increases median overall survival of newly diagnosed chemotherapy-naïve locally advanced or metastatic pancreatic cancer patients. Clinical trial information: NCT00561990.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors for locally advanced pancreatic cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 326-326
Author(s):  
Byung Min Lee ◽  
Seung Yeun Chung ◽  
Jee Suk Chang ◽  
Kyong Joo Lee ◽  
Si Young Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Pre Treatment

326 Background: It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and in combination would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. Methods: A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR < 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR < 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Results: Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR < 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR < 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR < 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p = 0.011) and PFS (p = 0.026). PLR > 149 also proved to be a significant factor for poorer OS (p = 0.003) and PFS (p = 0.021). Conclusions: Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. Pre-treatment NLR and PLR are useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.

A multicenter, phase IV study of the effectiveness of palliative gemcitabine in patients with advanced pancreatic cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 46-46
Author(s):  
David Wallace ◽  
Jina Zhang-Salomons ◽  
Christopher M. Booth ◽  
William J. Mackillop
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Clinical Practice ◽  
Clinical Benefit ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Well Being ◽  
Routine Clinical Practice ◽  
Assessment System ◽  
Patient Reported

46 Background: Randomized controlled trials (RCTs) have shown that palliative gemcitabine provides clinical benefit and prolongs survival in patients with advanced pancreatic cancer. The purpose of this study was to determine if the efficacy of palliative gemcitabine demonstrated in RCTs has translated into effectiveness in routine clinical practice in Ontario. Methods: This was a retrospective cohort study of all patients with exocrine cancer of the pancreas treated with first line, single agent, palliative gemcitabine at all 13 provincial cancer centres in Ontario between 2008 and 2011. These patients were identified by linking electronic records of treatment from all cancer centres and hospitals in Ontario to the Ontario Cancer Registry. Patient-reported well-being and symptoms were captured by the Edmonton Symptom Assessment System, which has been in routine use at these centres since 2008. The effectiveness of gemcitabine was measured in terms of clinical benefit at two months and overall survival. Patients were classified as having achieved clinical benefit if they had not discontinued gemcitabine and their self-reported well-being was stable or improved at two months. Results: The study population included 423 patients. Their median age was 65 and 50% were women. Fifty-seven percent had stage IV disease, 17% had stage III disease, and 10% had recurrence after earlier treatment for stage I or II disease. Patients included in this study were older than, but otherwise similar to, patients enrolled in four relevant RCTs that used gemcitabine in the experimental or control arm. At two months, 36.9% (95% CI 29.6-44.2%) of patients in this study achieved clinical benefit, which was within the range of 24% to 56% observed in patients in these trials. Median overall survival was 5.7 months (95% CI 4.7-6.1), which was within the range of 5.4 to 6.9 months reported in the trials. Conclusions: The efficacy of gemcitabine demonstrated in RCTs has translated into effectiveness in routine clinical practice in Ontario. The approach described above could readily be used to study the effectiveness of other palliative interventions.

scholarly journals Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
M. S. Walma ◽  
◽  
S. J. Rombouts ◽  
L. J. H. Brada ◽  
I. H. Borel Rinkes ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Radiofrequency Ablation ◽  
Controlled Trial ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Randomized Controlled ◽  
Link Type

Abstract Background Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26–34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. Methods The “Pancreatic Locally Advanced Unresectable Cancer Ablation” (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. Discussion The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. Trial registration Dutch Trial RegistryNL4997. Registered on December 29, 2015. ClinicalTrials.govNCT03690323. Retrospectively registered on October 1, 2018

scholarly journals Neoadjuvant Treatment in Locally Advanced Pancreatic Cancer (LAPC) Patients with FOLFIRINOX or Gemcitabine NabPaclitaxel: A Single-Center Experience and a Literature Review

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 981 ◽  
Author(s):  
Fabiana Napolitano ◽  
Luigi Formisano ◽  
Alessandro Giardino ◽  
Roberto Girelli ◽  
Alberto Servetto ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Disease Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Single Center Experience ◽  
Number Of Patients

The optimal therapeutic strategy for locally advanced pancreatic cancer patients (LAPC) has not yet been established. Our aim is to evaluate how surgery after neoadjuvant treatment with either FOLFIRINOX (FFN) or Gemcitabine-NabPaclitaxel (GemNab) affects the clinical outcome in these patients. LAPC patients treated at our institution were retrospectively analysed to reach this goal. The group characteristics were similar: 35 patients were treated with the FOLFIRINOX regimen and 21 patients with Gemcitabine Nab-Paclitaxel. The number of patients undergoing surgery was 14 in the FFN group (40%) and six in the GemNab group (28.6%). The median Disease-Free Survival (DFS) was 77.10 weeks in the FFN group and 58.65 weeks in the Gem Nab group (p = 0.625), while the median PFS in the unresected group was 49.4 weeks in the FFN group and 30.9 in the GemNab group (p = 0.0029, 95% CI 0.138–0.862, HR 0.345). The overall survival (OS) in the resected population needs a longer follow up to be completely assessed, while the median overall survival (mOS) in the FFN group was 72.10 weeks and 53.30 weeks for the GemNab group (p = 0.06) in the unresected population. Surgery is a valuable option for LAPC patients and it is able to induce a relevant survival advantage. FOLFIRINOX and Gem-NabPaclitaxel should be offered as first options to pancreatic cancer patients in the locally advanced setting.

scholarly journals C-Reactive Protein and Neutrophil/Lymphocytes Ratio: Prognostic Indicator for Doubling overall survival Prediction in Pancreatic Cancer Patients

2019 ◽  
Vol 8 (11) ◽  
pp. 1791 ◽  
Author(s):  
Schlick ◽  
Magnes ◽  
Huemer ◽  
Ratzinger ◽  
Weiss ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Disease Stage ◽  
C Reactive Protein ◽  
First Line ◽  
Reactive Protein ◽  
Two Factors

: Background: Despite modern chemotherapy regimens, survival of patients with locally advanced/metastatic pancreatic cancer remains dismal. Long-term survivors are rare and there are no prognostic scores to identify patients benefitting most from chemotherapy. Methods: This retrospective study includes 240 patients with pancreatic cancer who were treated in a primary palliative setting between the years 2007 to 2016 in a single academic institution. Survival rates were analyzed using the Kaplan–Meier method. Prognostic models including laboratory and clinical parameters were calculated using Cox proportional models in univariate and multivariate analyses. Results: Median age at diagnosis was 67 years (range 29–90 years), 52% were female and a majority had an ECOG performance status of 0 or 1. Locally advanced pancreatic cancer was diagnosed in 23.3% (n = 56) and primary metastatic disease in 76.7% (n = 184) of all patients. Median overall survival of the whole study cohort was 8.3 months. Investigating potential risk factors like patient characteristics, tumor marker or inflammatory markers, multivariate survival analysis found CRP (c-reactive protein) and NLR (neutrophil to lymphocyte ratio) elevation before the start of palliative chemotherapy to be independent negative prognostic factors for OS (overall survival) (p < 0.001 and p < 0.01). Grouping patients with no risk factor versus patients with one or two of the above mentioned two risk factors, we found a median OS of 16.8 months and 9.4 months (p < 0.001) respectively. By combining these two factors, we were also able to identify pancreatic cancer patients that were more likely to receive any post first line therapy. These two risk factors are predictive for improved survival independent of disease stage (III or IV) and applied chemotherapy agents in first line. Conclusion: By combining these two factors, CRP and NLR, to create a score for OS, we propose a simple, new prognostic tool for OS prediction in pancreatic cancer.

Neoadjuvant chemotherapy improves outcomes of chemoradiation therapy for locally advanced pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4036-4036 ◽  
Author(s):  
V. Rana ◽  
S. Krishnan ◽  
J. L. Abbruzzese ◽  
H. Q. Xiong ◽  
G. R. Varadhachary ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Median Time ◽  
Induction Chemotherapy ◽  
Initial Treatment ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Chemoradiation Therapy ◽  
Locally Advanced Pancreatic Cancer

4036 Background: Two-thirds of all pancreatic cancer patients have radiographically detectable metastatic disease at the time of diagnosis. Most of the remaining patients have locally advanced, unresectable disease that is typically treated with either chemoradiation or chemotherapy alone. We explored the possible benefit of the use of consolidative chemoradiation after induction chemotherapy. Methods: Between December 1993 and October 2005, 318 patients with locally advanced, non-metastatic, pancreatic cancer were treated at our institution with concurrent chemoradiation therapy. All patients underwent CT staging and biopsy confirmed adenocarcinoma. 245 patients received chemoradiation (CR) as initial treatment while 73 patients received a median of 2.5 months of induction chemotherapy prior to chemoradiation (CCR). Radiosensitizers included 5FU (42%), gemcitabine (39%) and capecitabine (19%) and most patients (88%) received 30 Gy of radiation therapy. The most common induction chemotherapy regimens were gemcitabine and cisplatin (73%) and gemcitabine alone (15%). Results: All statistics are actuarial and calculated from date of initial treatment. Median follow-up was 5.5 months (range 1–63 months). For all patients, overall survival was 9.0 months and 2-year survival was 8%. Age, gender, histology, grade, radiation fractionation and concurrent chemotherapy regimen had no impact on outcomes on univariate analysis. However, overall survival was 8.5 months in the CR group and 11.9 months in the CCR group (p = 0.0004). Median time to local progression was 6.0 months in the CR group and 8.4 in the CCR group (p = 0.0055). Median time to distant progression was 5.8 months in the CR group and 9.5 months in the CCR group (p=0.0136). Conclusions: In one of the largest series of locally advanced pancreatic cancer patients, the use of induction chemotherapy followed by chemoradiation seems to prolong median survival over initial treatment with chemoradiation. By excluding patients who progress rapidly during induction chemotherapy, this approach presumably selects patients most likely to benefit from a local treatment modality. This strategy merits prospective evaluation. [Table: see text]

Apricot-P: A randomized placebo-controlled phase II study of COX-2 inhibitor apricoxib or placebo in combination with gemcitabine and erlotinib in advanced or metastatic adenocarcinoma of the pancreas.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 253-253 ◽  
Author(s):  
Manuel Modiano ◽  
George P. Keogh ◽  
Robert Manges ◽  
Philip J. Stella ◽  
Ginger Milne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Study Endpoint ◽  
Primary Study ◽  
Metastatic Adenocarcinoma ◽  
Cox 2 ◽  
Adenocarcinoma Of The Pancreas

253 Background: Apricoxib is an oral, selective inhibitor of COX-2. COX-2 and EGFR signaling regulate the dominant ERK/MAPK, AKT and ß-catenin pathways in pancreatic cancer; combinations of COX-2 and EGFR inhibitors are of particular interest in this disease. ß-catenin activity is implicated in gemcitabine resistance. In addition, apricoxib has been demonstrated to potently reverse EMT in xenograft models of pancreatic cancer. In a completed Phase II study NSCLC patients were selected based on a decrease in PGEM, a urinary biomarker of COX-2 activity. As pancreatic cancer patients overwhelmingly over express COX-2 PGEM was measured for the purpose of secondary analysis in this study. Methods: Pts with locally advanced or metastatic adenocarcinoma of the pancreas were treated with erlotinib 100 mg PO daily and apricoxib/placebo 400mg PO daily and gemcitabine per previously published schedule (Burris JCO 2007). The primary objective PFS. Results: 109 patients were randomized (70 AP/GE:39 P/GE). Characteristics were balanced between the arms, 63% had elevated baseline PGEM. Most common adverse events included; rash (69%), diarrhea (59%), nausea (59%) and fatigue (57%). Drug-related SAEs included GI bleeding, MI and CVA and were more numerous on the apricoxib arm. The primary study endpoint was not met, HR 0.7; 95% CI (NA, 1.2). Trends in OS favoring the addition of apricoxib were demonstrated in 2 subgroups; elevated baseline PGEM and pts with a ≥ 50% drop from baseline PGEM. Conclusions: This study is the first randomized placebo controlled trial combining chemotherapy with COX-2 inhibition and EGFR kinase inhibition. The apricoxib containing arm had increased GI toxicity including GI hemorrhage. Although the primary endpoint was not met, overall survival in patients with a PGEM response to COX-2 inhibition favored addition of apricoxib. Further study in a biomarker selected population is warranted. [Table: see text]

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