Oral chemotherapy as second-line treatment option for gemcitabine-refractory advanced pancreatic cancer with poor performance status.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 405-405
Author(s):  
Se Jun Park ◽  
Myung Ah Lee
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Dose Intensity ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Line Treatment ◽  
Second Line ◽  
Median Dose ◽  
Gemcitabine Refractory

405 Background: There is few data for effective second-line treatment in advanced pancreatic cancer, and most patients have poor performance status after progressive disease. We evaluated the efficacy, toxicity, and median dose intensity of oral chemotherapy, capecitabine, or TS-1 in gemcitabine-refractory advanced pancreatic cancer for second-line treatment. Methods: Patients who have progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between Jan. 2011 and Nov. 2017. These patients were treated with capecitabine or TS-1 as second-line treatment. Capecitabine were administered as 2,500 mg/m2 divided dose on day 1-14, followed by one week rest. In TS-1 group, TS-1 was taken orally based on patient’s BSA (60mg twice daily in BSA > 1.5, 50mg twice daily in BSA 1.25-1.5, and 40mg twice daily in BSA < 1.25) through 28 days, by two week rest. Median dose intensity was compared by calculating a percent of target dose achieved in the average cycle for each patient. Results: Of the total 62 patients, 41 patients were treated with capecitabine and 21 patients were treated with TS-1. The median age was 61 years for the capecitabine group compared with 62 years for the TS-1 group. In capecitabine group, males were 56%, and in TS-1 group, males were 66%. 29% of capecitabine group received prior fluorouracil base therapy, and 47% of TS-1 group were receiving such therapy. The objective response rate was similar in the two groups: 12.2% with capecitabine and 4.8% with TS-1 (p = 0.358). There was no difference in median progression free survival between capecitabine and TS-1 (2.1 months vs. 2.7 months, p = 0.102), however, TS-1 group showed better median overall survival time than capecitabine group (6.9 months vs. 4.6 months, p = 0.048). Most of the adverse events were similar in both group, except that grade 3 or 4 mucositis was more common in TS-1 group. There was no significant difference in median dose intensity between two groups. (Capecitabine 91.5% vs. TS-1 90.1%, p = 0.216). Conclusions: Oral agents such as TS-1 or capecitabine can be second-line treatment for advanced pancreatic cancer patients with poor performance status after progression to gemcitabine-based regimen.

scholarly journals Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer

2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Weekly Schedule ◽  
Dose Reductions

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.

Clinical significance of serum alkaline phosphatase level in advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 183-183 ◽  
Author(s):  
I. Ohno ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
S. Shimizu ◽  
H. Takahashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Prognostic Factor ◽  
Performance Status ◽  
Elevated Serum ◽  
Advanced Pancreatic Cancer ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Bile Stasis ◽  
Low Serum

183 Background: Alkaline phosphatase (ALP) is an enzyme that is elevated by various hepatobiliary diseases. Generally its elevation is thought to indicate bile stasis. There are some reports that show ALP is an important prognostic factor for several cancers such as colon, lung, and gastric cancer. Often it is speculated that ALP elevation indicates bile stasis caused by liver metastasis. However, the significance of ALP elevation in advanced pancreatic cancer (APC) patients is not well evaluated. The aim of this study was to determine the significance of elevated serum ALP as a prognostic factor in patients with APC even without jaundice and liver metastasis. Methods: Serum ALP levels were measured in 393 patients with APC receiving gemcitabine monotherapy before treatment, and according to those levels, patients were subgrouped (ALP<upper normal limit (UNL), UNL-500 U/L, 501-700 U/L, 701-1000 U/L, 1000U/L < ALP). The clinical data of each group were analyzed to see characteristics of elevated ALP patients. The relationship between ALP level and survival, response were also examined. Results: The elevated ALP group included poor performance status (PS>1) patients (41.3%, p=0.001), and associated with low serum albumin (3.31±0.38, p<0.01). The elevated ALP group (median survival time (MST) 112 days) showed significantly worse prognosis and lower disease control rate compared to the normal ALP group (MST 217days) (p<0.001, p<0.001). Multivariate analysis revealed ALP (p<0.001), CRP (p<0.001), ascites (p<0.001), distant metastasis (p=0.003), white blood cell count (p=0.005), PS (p=0.020), AST (p=0.020), and ALT (p=0.020) were independent prognostic factors. Similar results were seen in liver metastasis free patients without jaundice. Conclusions: Elevated serum ALP level correlated with poor performance status and low serum albumin. ALP was also the independent prognostic factor in liver metastasis free APC patients without jaundice. No significant financial relationships to disclose.

Modified FOLFIRINOX as a second-line treatment in pancreatic adenocarcinoma patients with poor performance status.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15796-e15796
Author(s):  
Adarsh Das ◽  
Andrew Peter Dean ◽  
Domenic Higgs
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Locally Advanced ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Line Treatment ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Metastatic Pancreatic Adenocarcinoma

e15796 Background: FOLFIRINOX is well known to be a highly effective treatment in pancreatic cancer for young patients with good performance status. As the original ACCORD study was carried out with patient’s performance status 0 or 1, many oncologists feel uncertain administering modified dose FOLFIRINOX (m-FOLFIRINOX) as a second-line therapy. We have previously reported our experience in 35 patients (aged 27 – 85) where we concluded that m-FOLFIRINOX can be administered safely with appropriate dose reductions. More recently, the systematic review and meta-analysis by Tong et al. concluded that m-FOLFIRINOX is a good choice of therapy even for those with poor performance status. This retrospective analysis assessed the efficacy of m-FOLFIRINOX in second-line treatment of pancreatic adenocarcinoma. Methods: Using an electronic database, patients with either locally advanced or metastatic pancreatic adenocarcinoma were identified who had received first-line gemcitabine plus nab-paclitaxel, followed by second-line m-FOLFIRINOX between January 2013 and July 2018. All patients had an ECOG performance status of 2 or less. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Fifty-two patients were identified, with 65% of the patients having metastatic pancreatic disease. Median age of patients was 75 (range, 27 – 86). Dose intensity of m-FOLFIRINOX was 65% for oxaliplatin, 68% for irinotecan, 18% for bolus 5-fluorouracil (5-FU) and 68% for infusional 5-FU. From diagnosis, the median OS of all patients was 45.0 months (95% CI, 25.0 – 63.0). The median OS of the locally advanced and metastatic pancreatic adenocarcinoma was 63.0 months (95% CI, 45.0 – 70.0) and 22.5 months (95% CI, 18.0, 38.0), respectively. Conclusions: Our study demonstrates the safety and efficacy of m-FOLFIRINOX as a second-line therapy after gemcitabine plus nab-paclitaxel failure. These findings correlate with the findings of Tong et al.’s findings of the benefits of m-FOLFIRINOX for advanced pancreatic cancer in patients with poor performance status.

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4666-TPS4666
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Geert-Yan Creemers ◽  
Antonio Cubillo ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3

TPS4666 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment(NCT02195180). Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC is established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. IDMC last reviewed the trial in October 2019 and suggested the trial continue as planned. Clinical trial information: NCT03665441 .

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS783-TPS783
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Eric Van Cutsem ◽  
Jaime Feliu ◽  
Richard Greil ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3

TPS783 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment. Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC will be established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. Clinical trial information: NCT03665441.

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