The biomarkers of gemcitabine and erlotinib treatment in advanced pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 358-358
Author(s):  
Kuniyasu Irie ◽  
Makoto Ueno ◽  
Satoshi Kobayashi ◽  
Yoshihiro Gouda ◽  
Shinichi Ohkawa ◽  
...  

358 Background: A combination of gemcitabine+erlotinib is one of the standard chemotherapies in advanced pancreatic cancer (APC). Since APC patients often take antiulcer drugs to prevent gastritis (e.g., NSAIDs to reduce cancer pain), erlotinib concentration is generally decreased through the mechanism of CYP3A4. Furthermore, unlike lung cancer, the biomarkers for APC are not obvious except rash. Here, we examined biomarkers of gemcitabine+erlotinib treatment in APC patients including the presence of antiulcer drugs. Methods: The subjects were 59 advanced pancreatic cancer patients. They were treated with gemcitabine+erlotinib starting from Nov. 2011 to Apr. 2013. Gemcitabine was administered at 1000 mg/m2, on days 1, 8, and 15 for every 4 weeks, and erlotinib was taken 100 mg daily. The progression-free survival (PFS), UICC stage, sex, age, CRP concentration, performance status (PS), rash, and presence of antiulcer drugs were examined. The PFS curve was plotted according to the method of Kaplan and Meier. The difference in the PFS was calculated using the log-rank test, and a multivariate analysis was conducted using Cox hazard model. Results: UICC stages were as follows; i.e., stage II: 1, stage III: 8, and stage IV: 50. There were 36 males and 23 females, and their ages ranged from 41 to 82 years old (median: 65). The CRP concentrations ranged from 0.02 to 11.5 mg/dl (median: 0.57). 37 patients received antiulcer drugs, and 48 patients had rash. The univariate analysis revealed that the CRP concentration and rash were significant (p=0.009 and p=0.005, respectively). Low CRP (<0.57mg/dl) and presence of rash were related to good PFS. The multivariate analysis also revealed that the CRP concentration (HR, 0.34; 95%CI, 0.16-072; p=0.005) and rash (HR, 0.40; 95%CI, 0.16-0.96; p=0.04) were significant. The presence of antiulcer drugs on PFS was insignificant. Conclusions: The CRP concentration and rash were biomarkers of gemcitabine+erlotinib treatment in APC patients.

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). Results The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7–85.2; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2–86.4; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. Conclusions This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicity between radiation therapy (RT) with concurrent retrograde super-selective intra-arterial chemotherapy (IACRT) and RT with concurrent systemic chemoradiotherapy (SCRT), for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: Median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT group: 60 Gy; SCRT group:69 Gy). At 3 years, the two groups significantly differed in overall survival (OS; IACRT: 78.75%, 95% confidence interval [CI]: 66.00–87.62; SCRT: 50.37%, 95% CI: 27.58–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.64%, 95% CI: 62.69–85.17; SCRT: 41.96%, 95% CI: 17.65–70.90; P = 0.028) and local control (LC; IACRT: 77.17%, 95% CI: 64.23–86.41; SCRT: 41.96%, 95% CI: 17.65–70.90; P = 0.015). In univariate analysis, age ≥ 65, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with poor OS (P < 0.05). Patients with poorer PS had significantly worse PFS.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. IACRT is an effective and organ-preserving treatment for GC.Trial registration: retrospectively registered


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15743-e15743
Author(s):  
Ines Vendrell ◽  
Arlindo Rebelo Ferreira ◽  
Catarina Pulido ◽  
Anuraj Parmanande ◽  
Filipa Ferreira Da Silva ◽  
...  

e15743 Background: NG is a standard 1st line treatment for APC. Although recommended in 2nd line after FOLFIRINOX, there is little evidence of its efficacy, tolerability and of markers of efficacy. Methods: We performed a multicenter retrospective cohort study, including patients (pts) with APC from 5 centers in Portugal treated with 2nd line NG after 1st line FOLFIRINOX from 01/2013-12/2016. We collected demographic, clinicopathological characteristics and treatment data. We used descriptive statistics, Kaplan-Meier methods and Cox proportional hazards analysis. Results: 30 pts were included; median age was 64 years (range 45–78); the majority had stage IV (90%) disease, an ECOG Performance Status of 0 (76.7%) and had received a median of 8.5 cycles of FOLFIRINOX (range 1–18). A median of 6 cycles of NG were administered (range 1–13). Median progression free survival (PFS) and overall survival (OS) were 6.4 months (CI 95% 3.0-8.5) and 11.4 months (CI 95% 8.4–16.5), respectively, and did not differ by age < 65 or ≥65 (p = 0.87; p = 0.57 respectively). The most frequent toxicity was fatigue (66.6%, any grade). Grade 3-4 events occurred in 40% of pts – thrombocytopenia in 16.7%, neutropenia in 10.0%; anemia, sensorial neuropathy, fatigue and diarrhea each occurred in 3.3% of patients. No febrile neutropenia events or toxic deaths occurred. Median CA 19.9 at the beginning of NG was 1254U/mL (IQR: 207–6775); the median decrease of CA19.9 at 3 months was 45U/mL (IQR:-1373– +174). CA 19.9 variation at 3 months did not correlate with PFS (p = 0.53) or OS (p = 0.09) in multivariate analysis (adjusted for age and stage at diagnosis). Neutrophil to Lymphocyte ratio (NLR) was high ( > 3.0) in 37.5% of patients before 1st line treatment and in 27.6% at the beginning of NG. In multivariate analysis NLR before 1st or 2nd chemotherapy lines were not associated with PFS (p = 0.39; p = 0.14 respectively) or OS (p = 0.44; p = 0.12, respectively). Conclusions: In this cohort of pts with APC, NG was an effective and well tolerated 2nd line regimen after FOLFIRINOX failure, even in pts ≥65 years. Neither CA19.9 variation at 3 months nor NLR were markers of NG clinical benefit.


2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.


2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  

Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan–Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. Results: A total of 73 patients (median age: 73 years; range: 66–93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. Conclusion: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
R. T. Shroff ◽  
M. M. Javle ◽  
X. Dong ◽  
V. S. Kumar ◽  
S. Krishnan ◽  
...  

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15637-e15637
Author(s):  
M. Haas ◽  
S. Boeck ◽  
P. Stieber ◽  
R. P. Laubender ◽  
H. Buchner ◽  
...  

e15637 Background: Previous studies showed contradictory results for a predictive role of CA 19–9 kinetics during chemotherapy in patients (pts) with pancreatic cancer (PC). Methods: We performed a retrospective, multicenter study in order to evaluate the role of CA 19–9 as a biomarker for TTP and OS in PC. Main inclusion criteria: histological confirmed diagnosis of PC, treatment with first-line chemotherapy for advanced disease, pre-treatment CA 19–9 level of > 5.2 U/ml. As CA 19–9 measurements were conducted in different laboratories using different commercial assays, we defined a subgroup of pts where CA 19–9 was assessed exclusively by the Elecsys assay (Roche Diagnostics). For the analysis of CA 19–9 kinetics, at least one follow-up measurement between day 20 and 64 during first-line chemotherapy had to be available. Pts were divided into two subgroups of CA 19–9 responders and non-responders by cut-offs of a 25% and 50% decline, respectively. OS and TTP were estimated with the Kaplan-Meier-Method, differences between the subgroups were analyzed by using the log-rank test. Results: One hundred and eighty-six pts were included, 83 of them were tested with the Elecsys method. Median age was 63 years, 90 % of the pts were treated within prospective clinical trials. Median pre-treatment CA 19–9 was 1076 U/ml (range 5.7–100,000 U/ml), the median bilirubin was 0.6 mg/dl. Median OS and TTP were 9.8 months (mo) and 5.4 mo, respectively. In univariate analysis, pts with a CA 19–9 decline of at least 25% during chemotherapy lived significantly longer (11.9 mo vs. 8.2 mo, p=0.003) and had a significantly prolonged TTP (5.8 mo vs. 4.4 mo, p=0.018) than those with a lower decline or even CA 19–9 increase. Data for the Elecsys-measurements were comparable (OS: 13.4 mo vs. 8.6 mo, p=0.004; TTP: 7.0 mo vs. 2.6 mo, p=0.003). None of the analyses demanding a CA 19–9 drop of at least 50% reached the level of statistical significance. Conclusion: An early CA 19–9 decline of 25% during first-line chemotherapy may predict OS and TTP in pts with advanced PC. Innovative statistical methods are required to improve our understanding of the utility of CA 19–9 as a predictive biomarker in PC. [Table: see text]


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 265-265
Author(s):  
Shuichi Mitsunaga ◽  
Kumiko Umemoto ◽  
Kazuo Watanabe ◽  
Hiroyuki Okuyama ◽  
Yusuke Hashimoto ◽  
...  

265 Background: The serum tumor-marker in monitoring response to chemotherapy is not valid in advanced pancreatic cancer (PC). S100 calcium-binding protein P (S100P) has been reported as a predictive diagnostic index for PC and may serve as an early marker to activity of chemotherapy. The aim of this study was to analyze the correlation between the efficacies of chemotherapy and the kinetics of tumor-markers including serum S100P, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in prospective cohort of advanced PC. Methods: Patients who were treatment naïve for advanced PC with liver mets were eligible. Serum levels of S100P, CEA, and CA19-9 were measured at baseline and at one month later. The patients without monitoring of tumor-markers were excluded. A response of tumor-marker was defined as a decrease of at least 25%. Clinical data including radiological response according to the Response Evaluation Criteria In Solid Tumors ver. 1.1 were prospectively collected. S100P, CEA, and CA19-9 responses were tested in association with progression free survival (PFS) and overall survival (OS). Results: Fifty patients were analyzed in this study (male: 64%, median age: 67 years, Eastern Cooperative Oncology Group performance status [PS] 0: 60%). All of 50 patients received chemotherapy (gemcitabine [GEM]: 13 pts, GEM doublets: 34 pts, 5FU-based regimen: 3 pts). PFS and OS were 2.8 and 6.1 months. Responses of S100P, CEA, and CA19-9 were founded in 50%, 16%, and 32% of all, respectively. Multivariate analysis for PFS in Cox regression hazard model was performed using age, gender, PS, CEA, CA19-9, and S100P, and revealed that the independent predictors to longer PFS were responses of S100P (HR to progression: 0.47, P=0.02) and CEA (HR: 0.29, P=0.01). S100P or CEA responders showed better OS in univariate analysis using log-rank test, compared to non-responders of S100P (responder vs. non-responder: 8.4 vs. 3.7 months, P=0.04) or CEA (12.0 vs. 5.9 months, P=0.02), but not in multivariate analysis. Conclusions: Biochemical response of S100P might be useful for monitoring response to chemotherapy in advanced PC, which warranted further study in relationship between serum S100P response and treatment efficacies.


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