Phase I study of oral fluoropyrimidine anticancer agent (S-1) with concurrent external-beam radiotherapy for unresectable pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4109-4109
Author(s):  
H. Shinchi ◽  
S. Takao ◽  
K. Maemura ◽  
H. Noma ◽  
T. Aikou
Keyword(s):  
Pancreatic Cancer ◽  
Anticancer Agent ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
External Beam ◽  
Unresectable Pancreatic Cancer ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

4109 Background: S-1 is an oral fluorouracil anticancer agent that was recently reported to demonstrate a response rate of 21% in 19 patients with advanced pancreatic cancer. Concurrent external-beam radiotherapy (EBRT) and 5-FU has been generally accepted as the standard treatment for locally advanced pancreatic cancer. However, there are no published data regarding the efficacy of combination therapy of S-1 and radiation in patients with pancreatic cancer. Our purpose of this study was to evaluate the safety of S-1 combined with EBRT and determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1 in patients with locally advanced and unresectable pancreatic cancer. Methods: Eligible patients had UICC stage III or IV pancreatic cancer (either advanced unresectable or metastatic), adequate organ function, and no anticancer therapy in the preceding 4 weeks. S-1 was given orally at a dose of 60 mg/m2/day or 80 mg/m2/day in two divided doses after breakfast and supper. External-beam radiotherapy was delivered using a conformal technique in fraction of 1.25 Gy X 2/day, 5 days per week, totaling 50 Gy/40 fraction for 4weeks. S-1 at a dose of 60 mg/m2/day was given on days 1–7 and 15–21 in level 1, on days 1–14 in level 2, on days 1–21 in level 3a, respectively. S-1 at a dose of 80 mg/m2/day was given on days 1–21 in level 3b and on days 1–28 in level 4. DLT was defined as NCI-CTC grade 3/4 toxicity. Results: 18 patients were entered in this phase I trial: level 1 (4 patients), level 2 (5 patients), level 3a (3 patients), level 3b (3 patients), level 4 (3 patients). There were 1 of 5 patients with DLT in level 2: grade 3 vomiting. There were no DLT in levels 1, 3a, and 3b, respectively. Two of 3 patients in level 4 showed DLT: one patient developed grade 3 neutropenia and another patient developed grade 3 diarrhea. Clinical effects by CT scan included one PR, 15 SD and 2 PD. Reduced CA19–9 level less than a half of that at starting time was observed in 6 of 18 patients. Conclusions: S-1 at a dose of 80 mg/m2/day given on days 1–21 is safe and may be recommended for phase II study in patients with locally advanced and unresectable pancreatic cancer. This regimen appears to be a promising and well-tolerated approach with consideration of application to outpatients. No significant financial relationships to disclose.

A phase II trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent external-beam radiotherapy for locally advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15570-e15570
Author(s):  
H. Shinchi ◽  
K. Maemura ◽  
Y. Mataki ◽  
H. Kurahara ◽  
S. Natsugoe ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase I Trial ◽  
Anticancer Agent ◽  
Phase Ii Trial ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Unresectable Pancreatic Cancer

e15570 Background: S-1 is a new oral fluoropyrimidine anticancer agent and has shown a good efficacy for pancreatic cancer. In the phase I trial, we evaluated the safety of S-1 combined with external-beam radiotherapy (EBRT) to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients (H. Shinchi et al,, Br J Ca 2007;96:1353). The phase I trial determined the recommended of S-1 for the phase II chemoradiotherapy trial to be 80mg/m2/day given on days 1–21. This phase II trial was conducted to evaluate the efficacy and toxicity of EBRT combined with S-1 for locally advanced pancreatic cancer. Methods: Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, ECOG PS 0–1, adequate organ and marrow function, and no prior anticancer therapy. EBRT was delivered in fractions of 1.25Gy twice daily, totaling 50Gy per 40 fractions for 4 weeks. S-1 was given orally at a dose of 80mg/m2/day twice a day on days 1–21. The primary end-point of this trial was objective tumor response and secondary end-points included toxicity and overall survival. Results: Forty patients were enrolled in this phase II trial. Of the 40 patients, 39 (97%) completed the scheduled course of chemoradiotherapy. The objective tumor responses by RECIST criteria included 13 PR (33%), 20 SD (50%) and 7 PD (17%). The median survival time was 14 months and 1-year survival rate was 67%. Although grade 3 rash and anorexia occurred in one patient each, no grade 4 toxicities were observed. Conclusions: Combination therapy of S-1 and radiation shows favorable efficacy for locally advanced pancreatic cancer and was well tolerated with no severe toxicities. No significant financial relationships to disclose.

Phase I study of chemoradiation therapy (nab-paclitaxel/Gemcitabine) in 15 patients with unresectable locally advanced pancreatic cancer (UR-LAPC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 475-475 ◽  
Author(s):  
Hironari Sueyoshi ◽  
Tatsuya Ioka ◽  
Takeshi Tamura ◽  
Ryoji Takada ◽  
Nobuyasu Fukutake ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Standard Regimen ◽  
Level 3 ◽  
Level 1 ◽  
Level 2

475 Background: Pancreatic cancer (PC) is one of the most difficult cancers to treat. Over 90% of cases, they are UR-LAPC or metastatic PC (mPC) at the first time of diagnosis. To prolong survival time, radiation therapy is considered to be promising with strong local control. Some papers reported that RT with 5-FU is effective to LAPC, but they are far from standard regimen. Gemcitabine (Gem) has enhancing effect of sensibility to RT. Gem and nab-paclitaxel (G+NP) showed priority compared with Gem monotherapy in mPC patients with Phase III study. So, we performed Phase I study to decide recommended dose of G+NP when we administer for concurrent CRT in URPC patients. Methods: From Aug 2013, we have registered patients who were examined as UR-LAPC because of cancer invasion to major artery. Dose of G+NP are classified by each level. At Level 1, Gem 600mg/m2 and NP 50mg/m2. At Level 2, Gem 600mg/m2 and NP 75mg/m2. At Level 3, Gem 600mg/m2 and NP 100mg/m2. At each level, patients accepted RT (50.4Gy/28fr). During performing RT period, we prescribed G + NP weekly. So, G+NP are prescribed 4-5 times if pts accomplish the study.We evaluate effectiveness and side effect of the regimen, and try to decide maximum tolerated dose. Results: Until July 2014, 14 pts (11 males and 3 females) have been registered in this trial. 6 cases were performed at Level 1, 7cases at Level 2, 1 cases at Level 3. 13 cases accomplish the prescription. 1 case at Level 1 dropped out because the patient suffered liver abscess. Effectiveness of the regimen is as follows; 4cases are PD (progressive disease), 6cases are SD (stable disease), and 2cases are PR (partial response). Conclusions: Now we prescribe the regimen at Level 3. We have not yet decided MDT. But, CRT with G + NP may be promising regimen for LAPC. When we accumulate more cases, and decide MDT, we will report later. Clinical trial information: UMIN000012254.

Results of conversion surgery after the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 366-366
Author(s):  
Naoya Ikeda ◽  
Takahiro Akahori ◽  
Sohei Satoi ◽  
Hiroaki Yanagimoto ◽  
Minako Nagai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Clinical Impact ◽  
Ductal Adenocarcinoma ◽  
Unresectable Pancreatic Cancer ◽  
Conversion Surgery ◽  
Open Label ◽  
Grade 3 ◽  
Medical University

366 Background: Recent improvements in chemotherapy for initially unresectable pancreatic ductal adenocarcinoma (UPDAC) occasionally show remarkable antitumor effect and lead to conversion surgery (CS). However, the optimal indication and clinical impact of CS remains unknown. We have recently developed a new regimen consisted of biweekly S-1, oxaliplatin, and irinotecan (SOXIRI). In this regimen, we used S-1 in alternate-day administration instead of 5-FU, that can be more feasible than FOLFIRINOX. The aim of this study was to evaluate the clinical impact of CS after SOXILI treatment for initially UPDAC. Methods: We conducted an open-label, single-arm, phase II study that was carried out at Nara Medical University and Kansai Medical University in Japan. Patients with untreated metastatic and locally advanced PDAC were enrolled. They received 80 mg/m2 twice a day of S-1 for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results: The 35 enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8%; median OS, 17.7 months; and median PFS, 7.4 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). Twenty-three out of 35 patients of UR-PDAC were unresectable locally advanced pancreatic cancer (UR-LAPA). Seven out of 23 patients with UR-LAPA underwent CS. Distal pancreatectomy with celiac axis resection was performed in three patients, central pancreatectomy was performed in one patient. Pancreatoduodenectomy (PD) was performed in two patients, and PD with portal vein resection in one patient. Two out of seven patients had postoperative complications. One case had grade B pancreatic fistula, and the other case underwent cholecystectomy due to acute cholecystitis. The median OS in patients who received CS was 31.4 months. Conclusions: SOXIRI regimen has shown promising clinical efficacy with acceptable tolerability in patients with unresectable pancreatic cancer. Furthermore, it may be a potent first-line treatment when considering conversion surgery. Clinical trial information: UMIN000014339.

Phase II Study of Induction Chemotherapy with Gemcitabine plus 5-Fluorouracil Followed by Gemcitabine-Based Concurrent Chemoradiotherapy for Unresectable Locally Advanced Pancreatic Cancer

2006 ◽  
Vol 92 (6) ◽  
pp. 481-486 ◽  
Author(s):  
Ender Kurt ◽  
Meral Kurt ◽  
Ozkan Kanat ◽  
Sibel Kahraman Cetintas ◽  
Sevilcan Aygun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Disease Stabilization ◽  
Grade 3

Aims and background To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). Patients and methods Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. Results After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). Conclusions The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incor-poration of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

A phase 1 trial of GSL (gemcitabine, S-1, LV) combination therapy in advanced pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 290-290
Author(s):  
Yousuke Nakai ◽  
Hiroyuki Isayama ◽  
Takashi Sasaki ◽  
Kei Saito ◽  
Naminatsu Takahara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Tumor Response ◽  
Phase 1 ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Treatment Schedule ◽  
Phase 1 Trial ◽  
Level 1 ◽  
Grade 3

290 Background: Our previous randomized controlled trial, GEMSAP study (Br J Cancer. 2012 5;106:1934-9), showed a combination therapy of gemcitabine (Gem) & S-1 (GS) for advanced pancreatic cancer was superior to Gem monotherapy in terms of progression-free survival (PFS) but not overall survival (OS). Leucovorin (LV) is known to enhance efficacy of S-1 and we conducted this phase 1 trial of combination therapy of Gem, S-1 and LV (GSL). Methods: A primary endpoint of this classical “3+3” design phase 1 trial is to determine recommended dose of GSL. Inclusion criteria were 1. histologically-confirmed advanced pancreatic cancer without prior treatment, 2.PS 0-2, 3. age over 20. Treatment schedule was S-1 80 mg/m2 2x p.o. days 1-7, LV50mg 2x p.o. days 1-7, Gem 600(Level1), 800(Level2), 1000 mg/m2(Level3) div 30-min day 1 in a 2-week schedule. Dose-limiting toxicities were Grade 4 hematological and Grade ≥3 non-hematological toxicities, or delay of recovery from treatment-related toxicity for more than 2 weeks. Results: Between May 2012 and Feb 2013, 15 patients (Level 1/2/3: 6/6/3 patients) were enrolled; 7 males, a median age of 66, PS 0/1: 5/10, locally advanced/metastatic: 5/10. DLT was observed in 2/6 in Level 1 (Grade 3 anorexia in 1 and Grade 3 anorexia/stomatitis/diarrhea in 1) and 1/6 in Level 2 (Grade 3 pulmonary embolism). No DLT was observed in Level 3 and RD was determined as 1,000 mg/m2of Gem. Tumor response by RECIST was PR 5, SD 9, NE 1 with response rate of 33% and disease control rate of 93%. Overall toxicities greater than 3 were neutropenia 20%, anemia 7%, anorexia 13%, diarrhea 7%, stomatitis 7% and pneumonitis 7%. Conclusions: RD of GSL was determined as GEM 1000 mg/m2 div 30 min day 1, S-1 80 mg/m2 2x, LV50mg 2x p.o. days 1-7. GSL was tolerable and showed promising tumor response in advanced pancreatic cancer. Clinical trial information: UMIN000007556.

FOLFOX and nab-paclitaxel (nab-P) for advanced pancreatic cancer: A phase I study.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 258-258
Author(s):  
Howard Safran ◽  
Kevin Charpentier ◽  
Kimberly Perez ◽  
Kalyan Mantripragada ◽  
Trevor Clark Austin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Maximum Tolerated Dose ◽  
Level 3 ◽  
Grade 3 ◽  
Level 2

258 Background: FOLFIRINOX improves survival in advanced pancreatic cancer, however the contribution of irinotecan is uncertain. The addition of irinotecan to gemcitabine was not superior to gemcitabine alone in pancreatic cancer, however nab-P demonstrates a survival benefit. This phase I study was designed to evaluate the maximum tolerated dose (MTD) of the addition of nab-P to fluorouracil, leucovorin, oxaliplatin (FOLFOX-A). Methods: Patients with metastatic or locally advanced pancreatic adenocarcinoma without prior treatment received oxaliplatin, 85 mg/m2, leucovorin 400 mg/m2 and 5-FU 2400 mg/m2 with 3 dose levels of nab-P (125, 150 and 175 mg/m2) every 2 weeks. Pegfilgrastim was required during the first 2 cycles. Dose limiting toxicities (DLTs) were defined in the first 2 cycles of treatment. Results: Fifteen patients were entered: Dose level 1 (n=6), dose level 2 (N=6), dose level 3 (N=3). The median age was 64 (35-81). Ten patients had metastatic and 5 had locally advanced disease. DLTs of nausea and fatigue occurred in 2 of 3 patients at dose level 3. Two patients developed grade 3 neuropathy after >= 10 cycles of treatment. One patient had grade 3/4 neutropenia. Eight of fifteen patients (53%) had a partial response. Conclusions: The MTD of nab-P is 150mg/m2 every 2 weeks with FOLFOX. Cumulative peripheral neuropathy, similar to other FOLFOX regimens, is the most significant toxicity generally occurring after >= 10 cycles of treatment. FOLFOX-A has substantial activity and may represent a promising regimen in pancreatic cancer. Patients are currently being accrued to an expansion phase utilizing dose level 2. Supported by the Davis and Browning families and LIFEcycle. Clinical trial information: NCT01744353.

A Critical Overview of Systematic Reviews of Chemotherapy for Advanced and Locally Advanced Pancreatic Cancer using both AMSTAR2 and ROBIS as Quality Assessment Tools

2020 ◽  
Vol 15 ◽  
Author(s):  
Amit Dang ◽  
Surendar Chidirala ◽  
Prashanth Veeranki ◽  
BN Vallish
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Systematic Reviews ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Risk Of Bias ◽  
Low Risk ◽  
Locally Advanced Pancreatic Cancer ◽  
Grade 3 ◽  
Critical Overview

Background: We performed a critical overview of published systematic reviews (SRs) of chemotherapy for advanced and locally advanced pancreatic cancer, and evaluated their quality using AMSTAR2 and ROBIS tools. Materials and Methods: PubMed and Cochrane Central Library were searched for SRs on 13th June 2020. SRs with metaanalysis which included only randomized controlled trials and that had assessed chemotherapy as one of the treatment arms were included. The outcome measures, which were looked into, were progression-free survival (PFS), overall survival (OS), and adverse events (AEs) of grade 3 or above. Two reviewers independently assessed all the SRs with both ROBIS and AMSTAR2. Results: Out of the 1,879 identified records, 26 SRs were included for the overview. Most SRs had concluded that gemcitabine-based combination regimes, prolonged OS and PFS, but increased the incidence of grade 3-4 toxicities, when compared to gemcitabine monotherapy, but survival benefits were not consistent when gemcitabine was combined with molecular targeted agents. As per ROBIS, 24/26 SRs had high risk of bias, with only 1/26 SR having low risk of bias. As per AMSTAR2, 25/26 SRs had critically low, and 1/26 SR had low, confidence in the results. The study which scored ‘low’ risk of bias in ROBIS scored ‘low confidence in results’ in AMSTAR2. The inter-rater reliability for scoring the overall confidence in the SRs with AMSTAR2 and the overall domain in ROBIS was substantial; ROBIS: kappa=0.785, SEM=0.207, p<0.001; AMSTAR2: kappa=0.649, SEM=0.323, p<0.001. Conclusion: Gemcitabine-based combination regimens can prolong OS and PFS but also worsen AEs when compared to gemcitabine monotherapy. The included SRs have an overall low methodological quality and high risk of bias as per AMSTAR2 and ROBIS respectively.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

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