Clinical significance of elevation of the serum IL-6 level in patients with advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 181-181
Author(s):  
S. Mitsunaga ◽  
M. Ikeda ◽  
K. Nakachi ◽  
I. Ohno ◽  
S. Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Volume ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Japanese Version ◽  
Serum Levels ◽  
Ecog Performance Status ◽  
Reactive Protein ◽  
Treatment Naïve ◽  
Median Change

181 Background: IL-6, one of the pro-inflammatory cytokines, is a recognized mediator of cachexia and cancer cell invasion. It has been reported that elevation of the serum IL-6 level may be associated with deterioration of the clinical condition and tumor progression in advanced pancreatic cancer (PC) patients. The aim of this study was to clarify the clinical features of increased serum IL-6 levels in patients with advanced PC receiving chemotherapy. Methods: Patients with treatment-naïve unresectable PC and no obvious infectious conditions were eligible for this study. Serum levels of IL-6 were measured by an electrochemiluminescence assay. Symptoms were rated numerically from 0 to 10 using the Japanese version of the M. D. Anderson Symptom Inventory. Tumor volume was calculated as the sum of the long diameters of the tumors. The measurements were performed before chemotherapy and at one month after the start of chemotherapy. Results: A total of 87 patients (male/female: 41/46; ECOG performance status: 0/1/2: 59/26/1; media age: 66 years) were enrolled; all patients were administered systemic chemotherapy (gemcitabine [GEM]/GEM+S-1/GEM+other/S-1: 52/11/9/15). The median serum level of IL-6 was 1.3 pg/mL before chemotherapy (at baseline) and 1.8 pg/mL at one-month after the start of chemotherapy. The median change of IL-6 from the baseline was +0.18 pg/mL. Patients with increase of the serum IL-6 level by more than 0.18 pg/mL were assigned to the elevated IL-6 group (n=42; median change in IL-6: +1.66 pg/mL). The elevated IL-6 group showed more sadness (p=0.019), numbness (p=0.008), and gain of body weight (p=0.016) at the baseline as compared to the non-IL-6-elevated group (n=42; median change in IL-6: -0.27 pg/mL). Comparison of the elevated and non-IL-6-elevated groups revealed a greater degree of increase in the tumor volume (p=0.015), deterioration of nausea (p=0.046) and vomiting (p=0.028), neutrophilia (p=0.004), and elevation of the serum C-reactive protein (p=0.011) in the elevated IL-6 group than in the non-IL-6-elevated group. Conclusions: Elevation of the serum IL-6 level may be associated withsymptom deterioration, increase of the tumor mass, and inflammatory reaction in patients with advanced PC. No significant financial relationships to disclose.

Association of interleukin-6 levels and neutropenia during gemcitabine monotherapy for advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 178-178 ◽  
Author(s):  
H. Okuyama ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
I. Ohno ◽  
S. Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Inflammatory Cytokines ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Severe Neutropenia ◽  
Ecog Performance Status ◽  
Tnf Α ◽  
Low Serum ◽  
Pro Inflammatory Cytokines

178 Background: Neutropenia is an important dose-limiting toxicity of gemcitabine (GEM) in patients with advanced pancreatic cancer (PC). Serum haptoglobin, regulated by pro-inflammatory cytokines, is a predictor of neutropenia in PC patients under treatment with GEM. We conducted this study with the aim of identifying the association between serum levels of haptoglobin and cytokines and the risk of development of neutropenia in advanced PC patients receiving GEM therapy. Methods: Serum levels of haptoglobin and pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-2β, IL-6, IL-8, IL-10, IL-12, TNF-α) were measured in 55 patients with advanced PC. All patients (median age: 67 years, male/female: 26/29, ECOG performance status: 0/1/2: 32/21/2,) received GEM monotherapy as the initial treatment for PC. The severity of neutropenia within the first 90 days of the GEM treatment was graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Categorical or and noncategorical data were compared using Student's t test. Multivariate regression analysis was performed using logistic regression modeling. The significance level was set at p<0.05. Results: Grade 0 to 2 (G0/1/2) and grade 3 to 4 (G3/4) neutropenia were observed in 32 patients (58.2%) and 23 patients (41.8%), respectively. The G3/4 neutropenia group showed low serum levels of haptoglobin (mean 144.4 mg/dl vs. 186.7 mg/dl, p=0.097), IL-1β (mean 0.07 pg/ml vs. 0.24 pg/ml, p=0.044), IL-6 (mean 1.13 pg/ml vs. 6.43 pg/ml, p=0.002), IL-8 (mean 18.4 pg/ml vs. 44.8 pg/ml, p=0.015), and TNF-α (mean 6.28 pg/ml vs. 8.86 pg/ml, p=0.017) as compared to the G0/1/2 neutropenia group. Multivariate analysis revealed that only low serum IL-6 was significantly associated with the development of G3/4 neutropenia (OR=0.081, p=0.0011). Conclusions: Low serum IL-6 level was associated with severe neutropenia. Thus, circulating IL- 6 levels may be a predictor of the development of severe neutropenia in advanced PC patients receiving GEM therapy. No significant financial relationships to disclose.

Characterization of patients with high serum level of IL-6 in advanced pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 197-197
Author(s):  
Tomofumi Miura ◽  
Shuichi Mitsunaga ◽  
Satoshi Shimizu ◽  
Izumi Ohno ◽  
Hideaki Takahashi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Advanced Pancreatic Cancer ◽  
Disease Status ◽  
High Serum ◽  
Related Factor ◽  
Related Factors ◽  
Reactive Protein ◽  
Treatment Naïve

197 Background: IL-6 is a key mediator of cancer cachexia. The degree of cachexia affects serum IL-6 level in pancreatic cancer (PC) and is varied according to disease progression. The study population to characterize advanced PC patients with high IL-6 level needs the homogeneity in disease status. This study was aimed to identify IL-6-related factors in patients who were scheduled to undergo first-line chemotherapy for treatment-naïve advanced PC. Methods: Patients with treatment-naïve advanced PC were eligible for inclusion in this study. Patients with obvious infection or biliary drainage were excluded. Serum IL-6 levels and clinical parameters (e.g. symptoms, body composition) were prospectively collected. A high IL-6 level was defined as a value greater than the median value in all of the analyzed patients, and analyses were performed to identify risk factors for high IL-6 levels. Results: Eighty patients were analyzed. A multivariate analysis determined that the following parameters were associated with high IL-6: the presence of liver metastasis [Odds ratio (OR): 4.8, p < 0.01], fatigue (OR 3.4, p = 0.02), high carcinoembryonic antigen (CEA) levels (OR: 6.9, p = 0.03), anemia (OR: 9.5, p = 0.01), and high C-reactive protein (CRP) levels (OR: 12.4, p = 0.02). A decreased skeletal muscle mass tended to be frequently observed in patients with high IL-6 levels. Conclusions: High serum IL-6 related the presence of liver metastasis, severe fatigue, high CEA, high CRP and anaemia. Additionally, skeletal muscle loss might be the IL-6 related factor.

Identification of prognostic factors for patients with advanced pancreatic cancer by proteomics

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4615-4615
Author(s):  
J. Matsubara ◽  
M. Ono ◽  
H. Ueno ◽  
T. Okusaka ◽  
J. Furuse ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prediction Model ◽  
Statistical Significance ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Information Criterion ◽  
Survival Prediction ◽  
Current Standard ◽  
Ecog Performance Status ◽  
Wbc Count

4615 Background: Gemcitabine monotherapy is the current standard for patients with advanced pancreatic cancer (PC). Its efficacy, however, varies significantly depending on individuals. This study was aimed at discovering a new diagnostic biomarker that can estimate the outcome of patients after receiving the therapy. Methods: All patients included in this study (304 patients) had metastatic PC and received at least two cycles of gemcitabine monotherapy. We compared the baseline plasma proteome between representative 29 short-term survivors (survived for less than 100 days) and 31 long-term survivors (survived for more than 400 days) using quantitative mass spectrometry (MS). Results: Among a total of 45,277 peptide peaks, we identified 637 peaks whose intensities were significantly different (p<0.001, Welch's t-test). The 2 MS peaks with the highest statistical significance (p=2.57×10-4 and 5.03×10-4) were revealed to be derived from α1-antitrypsin (AT) and α1-antichymotrypsin (ACT), respectively, by tandem MS. The levels of AT and ACT, WBC count, platelet count, alkaline phosphatase, and ECOG performance status were selected using a forward stepwise procedure by Akaike's information criterion, and a scoring system (nomogram) was constructed to estimate the prognosis of individual patients. Among the selected parameters the AT level was found to be the second most significant contributor to the nomogram (p=0.0003; Table ). This survival prediction model was internally validated using a bootstrap approach with 200 resamples. Conclusions: Our survival prediction model including values of AT and ACT seems to have high practical utility and may lead to tailoring the treatment of patients with advanced PC. Modification of therapeutics may need to be taken into consideration for patients with increased AT and ACT. [Table: see text] [Table: see text]

Phase I trial of enzalutamide in combination with gemcitabine and nab-paclitaxel for the treatment of advanced pancreatic cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 467-467
Author(s):  
Amit Mahipal ◽  
Gregory M. Springett ◽  
Nancy Burke ◽  
Barbara Bertels ◽  
Georgine Wapinsky ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dose Level ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Treatment Standard ◽  
Cancer Models ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Grade 3

467 Background: Despite recent advances, patients with metastatic pancreatic cancer have a very poor prognosis with a median survival of less than 1 year. Sex steroid hormones may play an important role in the growth and progression of pancreatic cancer. Anti-androgen drugs have demonstrated to have activity in pre-clinical pancreatic cancer models. In this Phase 1a/Ib trial, we evaluated the safety and tolerability of the combination of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and nab-paclitaxel. Methods: Pts with histologically confirmed metastatic pancreatic adenocarcinoma were included in this trial as a first-line treatment. Standard 3+3 dose escalation design was used to evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg daily. Gemcitabine 1,000 mg/m2 was administered IV on days 1, 8 and 15 of 28-day cycle. The dose of nab-paclitaxel was 125 mg/m2 IV on days 1, 8 and 15. The DLT period was 28-days or until the beginning of the second cycle. Imaging studies were performed every 2 cycles. Results: Eight pts with stage IV pancreatic cancer have been enrolled in this trial, 5 pts at the first dose level and 3 pts at the second dose level. The median age was 64 years (50-80 years). All pts were male with an ECOG performance status of 1. Five pts had liver metastases. One patient was non-evaluable for DLT. No DLTs have been observed. Grade 3 treatment related AEs include febrile neutropenia (n=1), Neutropenia (n=1), ALT elevation (n=1). Grade 2 anemia and thrombocytopenia was seen in one patient. Grade 1 AEs included anemia (n=2), neutropenia (n=4), thrombocytopenia (n=3), diarrhea (n=1), fatigue (n=2), pruritis (n=1), nausea (n=1), hyponatremia (n=1) and AST elevation (n=1). Three pts had restaging studies performed and all had stable disease by RECIST criteria. There were decreases in size of target lesions in all the 3 patients along with a decrease in CA 19-9 levels. Conclusions: Enzalutamide at the dose of 160 mg daily is safe to administer in combination with gemcitabine and nab-paclitaxel. No unexpected toxicity has been observed. Cytopenias secondary to chemotherapy is common. Preliminary signals of efficacy were observed with this combination. Clinical trial information: NCT02138383.

scholarly journals Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4842
Author(s):  
Hidetaka Suzuki ◽  
Shuichi Mitsunaga ◽  
Masafumi Ikeda ◽  
Takao Aoyama ◽  
Kazumi Yoshizawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Group Performance ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Pancreatic Disease ◽  
High Serum ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.

Interim results of a multicenter phase II trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients (Pts) with locally advanced pancreatic cancer (LAPC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 358-358 ◽  
Author(s):  
Jill Lacy ◽  
Fabienne Portales ◽  
Pascal Hammel ◽  
Roberto A. Pazo Cid ◽  
Jose Luis Manzano Mozo ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Options ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Treatment Phase ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Eortc Qlq C30 ◽  
Treatment Naïve ◽  
Eortc Qlq

358 Background: Treatment options for pts with LAPC are limited and generally similar to those for metastatic PC (mPC). The phase 3 MPACT trial of pts with mPC demonstrated a > 3-fold shrinkage of primary tumors with nab-P + G vs G, suggesting the potential of nab-P + G for LAPC treatment. Here, we present interim results on disease control rate (DCR), adverse events (AEs), and quality of life (QoL) from the international phase 2 LAPACT trial. Methods: Pts with treatment-naive unresectable LAPC and ECOG performance status of 0 or 1 received 6 cycles (C) of nab-P 125 mg/m2 + G 1000 mg/m2 on days 1, 8, and 15 of each 28-day C. After the initial nab-P + G treatment phase, pts without PD and unacceptable AEs were eligible for investigator’s choice (IC) of continued treatment with nab-P + G, chemoradiation, or surgery. Surgery could occur prior to completing 6 C in the case of a major response. Pt-reported QoL was assessed via EORTC QLQ-C30 and QLQ-PAN26 questionnaires at screening and prior to infusion on day 1 of each C. Results: As of Aug 17, 2016, 47 pts completed (28/47, 60%) or discontinued (19/47, 40%) the initial nab-P + G treatment (median, 5 C). Median age was 66 years (range, 44 - 86). The most frequent reasons for discontinuation were AE (10/47 [21%], with the most common being neutropenia and abnormal liver function [2 pts each]) and PD (3/47, 6%). The most common grade ≥ 3 AEs were neutropenia (34%) and anemia (11%). The DCR ≥ 16 weeks was 76% (34/45 efficacy-evaluable pts [defined as having evaluable baseline and ≥ 1 postbaseline scan]; PR, n = 13; SD, n = 21). Twenty-two pts (47%) were assigned by the investigators to an IC treatment: 4 (9%) to continue nab-P + G, 8 (17%) to chemoradiation, and 10 (21%) to surgical resection. Mean QoL scores remained stable during the study, with improved symptom scores for appetite and pain. During the initial nab-P + G treatment phase, most patients reported a complete resolution of certain limitations, including depression (≈ 80%), constipation (≈ 62%), and nausea (≈ 93%). Conclusions: These interim results suggest that for pts with LAPC, nab-P + G is tolerable and produces a promising DCR. On average, QoL scores remained stable during nab-P + G treatments. Clinical trial information: NCT02301143.

Phase II Study of Oral L-Leucovorin, 120-Hour Fluorouracil Infusion and Carboplatin in Advanced Pancreatic Cancer

1996 ◽  
Vol 82 (6) ◽  
pp. 573-575 ◽  
Author(s):  
Marco Colleoni ◽  
Patrizia Nelli ◽  
Giovanni Vicario ◽  
Francesca Pancheri ◽  
Gigliola Sgarbossa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Carcinoma ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Treatment Schedule ◽  
Time To Progression ◽  
Ecog Performance Status ◽  
Advanced Pancreatic Carcinoma

Background No effective chemotherapy has been developed for patients with metastatic pancreatic cancer. Encouraging results have been reported with the combination of cisplatin and fluorouracil infusion. The aim of the study was to test the activity of oral L-leucovorin, carboplatin and fluorouracil infusion in untreated pancreatic cancer patients. Patients and Methods Patients with advanced pancreatic carcinoma were treated with carboplatin (300 mg/m2 on day 1), L-leucovorin (5 mg/m2 twice a day on days 1-5), and fluorouracil (1,000 mg/m2 as a 120-hr infusion on days 1-5), cycles being repeated every 21 days. Results Nine patients were included and were assessable for response and side effects. All patients had measurable disease and an ECOG performance status of 0-2. No patient achieved partial remission, 3 had stable disease, and 6 progressive disease. Median time to progression was 2 months (range, 2-8), and median survival was 4 months (range, 3-12). Toxicity consisted of mucositis, diarrhea and neutropenia. Conclusions Patients with metastatic pancreatic carcinoma do not benefit from this treatment schedule.

A phase II trial of oxaliplatin plus capecitabine (xelox) as second line therapy for patients with advanced pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4119-4119 ◽  
Author(s):  
H. Q. Xiong ◽  
R. A. Wolff ◽  
K. R. Hess ◽  
G. R. Varadhachary ◽  
J. C. Blais ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Survival Duration ◽  
Second Line ◽  
Second Line Therapy ◽  
Ecog Performance Status ◽  
Line Therapy ◽  
Measurable Disease ◽  
Ecog Ps

4119 Background: There is no established chemotherapy for patients with pancreatic cancer who have progressed on gemcitabine. This trial was designed to explore the efficacy of xelox as second line therapy in patients with pancreatic cancer. Methods: The primary objective was to determine overall survival at 6 months. It was estimated that 40 patients would be needed to detect 50% 6-month survival with 90% credible interval between 37%-62%. Eligibity criteria included biopsy-confirmed diagnosis of adenocarcinoma of the pancreas, one prior systemic chemotherapy, ECOG performance status (PS) 0–2, and adequate hepatic, renal, and bone marrow functions. Oxaliplatin was administered at 130 mg/m2 and capecitabine at 1000 mg/m2 twice daily for 14 days for patients who were younger than 65 and had ECOG PS score 0–1. For patients older than 65 or PS 2, the oxaliplatin dose was decreased to 110 mg/m2 and capecitabine to 750 mg/m2/twice daily. The treatment was repeated every 3 weeks. Tumor measurements were performed every 9 weeks (3 cycles) in patients who had measurable disease by RECIST criteria, although measurable disease was not required. Results: A total of 41 patients were enrolled into the study, 2 were never treated. Among 39 evaluable patients, 17 were female, median age 62 years (45–75), and 8 had ECOG PS 2. For the 36 patients who have completed therapy, the median number of treatment cycle was 3 (range, 1–6). Grade 3 or 4 toxicities included: abdominal pain (2 patients), dehydration (3), diarrhea (2), fatigue (6), gastrointestinal syndrome (including diarrhea and colitis) (4), hand-foot syndrome (1), hematemesis (1), mastitis (1), myocardial infarction (1), nausea/vomiting (2), neuropathy (1), non-neutropenic fever (1), pneumonia (1). One patient had a partial response and 8 others had stable disease. Median survival duration was 5.8 months (95% confidence interval [CI] 3.2–12.1 months). The six month and 1 year survival rate was 48% (95% CI 33%-70%) and 22% (95% CI 9%-51%), respectively. Conclusions: When used in the second line setting, the xelox has promising activity in pancreatic cancer. [Table: see text]

Tolerability and clinical outcomes in elderly patients with advanced pancreatic cancer treated with FOLFIRINOX.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 404-404 ◽  
Author(s):  
Taikan Yamamoto ◽  
Yu Sunakawa ◽  
Yutaro Kubota ◽  
Teppei Tagawa ◽  
Yasuhiro Kaga ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
The Elderly ◽  
Elderly Group ◽  
Severe Neutropenia ◽  
Severe Toxicity ◽  
Ecog Performance Status ◽  
Significant Difference

404 Background: FOLFIRINOX, a combination chemotherapy of 5-FU, oxaliplatin, and irinotecan, has contributed to the overall survival (OS) benefit of advanced pancreatic cancer (PC), of which a major concern is severe toxicity such as neutropenia and diarrhea. Some elderly patients (pts) with PC need such an intensive chemotherapy in practical treatment; however, tolerability and efficacy for the regimen in the elderly are not well known. We report a retrospective analysis for toxicity and efficacy of FOLFIRINOX treatment in elderly pts with advanced PC. Methods: We analyzed pts with unresectable/metastatic PC, ECOG performance status 0 or 1, neutrocyte over 1500/mm3, and hemoglobin over 9g/dl, who received FOLFIRINOX as 1st- or 2nd-line therapy between November 2012 and July 2015 in 3 institutes of Showa University, Japan. All pts were divided into two groups, elderly group with pts 65 years of age or older and younger group with pts under 65 years old, then were compared in the toxicity and efficacy of FOLFIRINOX treatment. Results: Fifty-nine pts (median age: 62 years) were enrolled in this study: elderly and younger groups included 26 pts (median age: 70 years) and 33 pts (median age: 57 years), respectively. Severe neutropenia with grade 4 was numerically more frequent in the elderly group compared to the younger group (54% vs. 36%, p = 0.17). However, rate of febrile neutropenia was similar between the groups: 3 (12%) pts for the elderly group and 2 (6%) pts for the younger group. There was no difference in frequency of any grade toxicities, and no FOLFIRINOX treatment-related death was observed in both groups. Response rate was 14% (5/26) for the elderly group and 33% (11/33) for the younger group, with no significant difference (p = 0.22). Median progression-free survival (PFS) and OS were comparable between the elderly and younger groups (5.3 months vs. 5.4 months, log-rank p = 0.47 for PFS; not-reached vs. 10.7 months, long-rank p = 0.49 for OS). Conclusions: Our study suggests that FOLFIRINOX treatment is tolerable and active for the elderly pts with advanced PC, although frequency of severe neutropenia is higher in the elderly compared to the younger pts.

Olaparib (O) in patients (pts) with pancreatic cancer with BRCA1/2 inactivating mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4637-4637
Author(s):  
Eugene R Ahn ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Pam K. Mangat ◽  
Carmen Julia Calfa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Elevated Liver Enzymes ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Inactivating Mutations

4637 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pancreatic cancer pts with germline or somatic BRCA1/2 inactivating mutations treated with O are reported. Methods: Eligible pts had advanced pancreatic cancer, no standard treatment (tx) options available, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received O tablets or capsules dosed at 300 mg (n=27) or 400 mg (n=3), respectively, orally twice daily until disease progression. Simon 2-stage design tested the null disease control (DC) (objective response (OR) or stable disease at 16+ weeks (wks) (SD16+) according to RECIST) rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS), and safety. Results: Thirty pts with BRCA1/2 inactivating mutations were enrolled from Nov 2016 to Aug 2019; 20 were previously treated with platinum based therapy. Two were not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One partial response (PR) and 7 SD16+ were observed for DC and OR rates of 31% (90% CI: 18% - 40%) and 4% (95% CI: 0% - 18%), respectively. Seven pts had at least one grade 3 AE or SAE at least possibly related to O including anemia, diarrhea, fever, elevated liver enzymes, enterocolitis, increased bilirubin, and oral mucositis. Conclusions: Monotherapy O showed anti-tumor activity in heavily pre-treated pts with pancreatic cancer with germline (5/12 pts with OR or SD16+) or somatic (3/16 pts with OR or SD16+) BRCA1/2 inactivating mutations extending findings of recent studies of O in pts with advanced pancreatic cancer. Clinical trial information: NCT02693535 . [Table: see text]

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