Second line treatment with 5-fluorouracil and folonic acid in gemcitabine- pretreated advanced pancreatic cancer

Introduction: Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. Methods: Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. Results: The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). Conclusions: GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

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P-0107 Gemcitabine and Cisplatin Combined with Regional Hyperthermia as Second-Line Treatment in Patients with Gemcitabine-Refractory Advanced Pancreatic Cancer

Annals of Oncology ◽

10.1016/s0923-7534(20)30025-9 ◽

2012 ◽

Vol 23 ◽

pp. iv62

Author(s):

Katharina Lechner ◽

Frank Berger ◽

Nelli Dieterle ◽

Sultan Abdel-Rahman ◽

Christoph Salat ◽

...

Keyword(s):

Pancreatic Cancer ◽

Advanced Pancreatic Cancer ◽

Line Treatment ◽

Second Line ◽

Regional Hyperthermia ◽

Gemcitabine Refractory ◽

Gemcitabine And Cisplatin

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Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15111 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15111-15111 ◽

Cited By ~ 1

Author(s):

Y. Park ◽

S. Yi ◽

H. Kim ◽

S. Lee ◽

I. Hwang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Stable Disease ◽

Single Agent ◽

Advanced Pancreatic Cancer ◽

Median Number ◽

Line Treatment ◽

Second Line ◽

Best Response ◽

Grade 3 ◽

Number Of Cycles

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.405 ◽

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.

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S-1 plus CIK as second-line treatment for advanced pancreatic cancer

Medical Oncology ◽

10.1007/s12032-013-0747-9 ◽

2013 ◽

Vol 30 (4) ◽

Cited By ~ 10

Author(s):

Meng Wang ◽

Sheng-bin Shi ◽

Jie-lin Qi ◽

Xiao-yong Tang ◽

Jing Tian

Keyword(s):

Pancreatic Cancer ◽

Advanced Pancreatic Cancer ◽

Line Treatment ◽

Second Line

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Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial

European Journal of Cancer ◽

10.1016/j.ejca.2019.10.020 ◽

2020 ◽

Vol 124 ◽

pp. 91-101 ◽

Cited By ~ 11

Author(s):

Pascal Hammel ◽

Portales Fabienne ◽

Laurent Mineur ◽

Jean-Philippe Metges ◽

Thierry Andre ◽

...

Keyword(s):

Pancreatic Cancer ◽

Advanced Pancreatic Cancer ◽

Line Treatment ◽

Second Line ◽

Open Label

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S-1 monotherapy or in combination with leucovorin as second-line treatment in gemcitabine-refractory advanced pancreatic cancer: A phase II study.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.e15222 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. e15222-e15222

Author(s):

Feijiao Ge ◽

Nong Xu ◽

Yuxian Bai ◽

Yi Ba ◽

Yanqiao Zhang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Advanced Pancreatic Cancer ◽

Line Treatment ◽

Second Line ◽

Gemcitabine Refractory

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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).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps4666 ◽

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 .

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Modified FOLFIRINOX versus S-1 as second-line chemotherapy in patients with gemcitabine-failed metastatic pancreatic cancer: A randomized phase III trial (MPACA-3).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4119 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4119-4119

Author(s):

Se-Il Go ◽

Sang-Cheol Lee ◽

Woo Kyun Bae ◽

Dae Young Zang ◽

Hyun Woo Lee ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Group Performance ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Advanced Pancreatic Cancer ◽

Phase Iii ◽

Line Treatment ◽

Second Line ◽

Phase Iii Trial

4119 Background: Modified FOLFIRINOX (mFOLFIRINOX) consisting of 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin has been assessed as second-line treatment of patients with advanced pancreatic cancer in retrospective and phase II studies. However, the result was not confirmed by randomized controlled trial. Methods: A randomized, open-label, phase III trial was conducted at 9 institutions in Korea. Patients with metastatic pancreatic adenocarcinoma (mPAC) and Eastern Cooperative Oncology Group performance status of 0-1 who failed to first-line gemcitabine-based chemotherapy were randomly assigned to receive mFOLFIRINOX or S-1. The primary endpoint was overall survival. Results: A total of 80 patients were enrolled from March 2017 to December 2019. The accrual of patients was early terminated due to clear difference of efficacy in the interim analysis and expectation of poor recruitment due to conflicting adjuvant regimens. Objective response and disease control rates were 15.4% vs. 2.4% ( p= 0.041) and 66.7% vs. 36.6% ( p= 0.007) in the mFOLFIRINOX and S-1 arms, respectively. The median progression-free survival was 5.2 and 2.2 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.002). The median overall survival was 9.2 and 4.9 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.048). The adjusted hazard ratio of the mFOLFIRINOX arm to the S-1 arm for overall survival was 0.402 (95% confidence interval 0.223-0.725, p= 0.002). All grade 3-4 adverse events occurred in 56.5% and 17.1% in the mFOLFIRINOX and S-1 arms, respectively ( p< 0.001). However, only one patient in each arm prematurely discontinued treatment due to toxicity and there was no treatment-related mortality in both arms. Minimally important differences in the health-related quality of life were not observed in both arms. Conclusions: mFOLFIRINOX as second-line treatment in mPAC patients failed to gemcitabine-based chemotherapy demonstrated a survival benefit versus S-1 alone with acceptable toxicities. Clinical trial information: KCT0003534.

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