Pharmacokinetically-guided 5-FU dose optimization within the preoperative FOLFOXIRI regimen in resectable pancreatic cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4636-4636
Author(s):  
Anna Vilalta ◽  
Amaia Urrizola Martínez ◽  
Azucena Aldaz ◽  
Pablo Sala Elarre ◽  
Mariano Ponz-Sarvisé ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Progression ◽  
Dose Intensity ◽  
Rank Test ◽  
Pharmacokinetic Parameters ◽  
R0 Resection ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Drug Concentrations ◽  
Grade 3

4636 Background: Neoadjuvant therapy is an increasingly used approach in patients with resectable pancreatic cancer (PC). A positive link between chemotherapy dose intensity and patients’ outcome has been suggested in PC. The aim of this study was to rule out whether 5-FU pharmacokinetic (PK) parameters correlate with outcome in resectable PC patients treated with preoperative FOLFOXIRI. Methods: Patients with resectable and borderline resectable PC treated with Oxaliplatin (85mg/m2), Leucovorin (400mg/m2), Irinotecan (150 mg/m2) and 5-FU (initial dose of 3200 mg/m2 in 46h infusion and subsequent doses based on PK-guided dose adjustements targeting an AUC of 25-30 mcg*h/ml) were included. 5-FU PK analysis was performed taking two plasma samples during 5-FU infusion in at least two cycles. Drug concentrations were analysed by High-Perfomanced Liquid Chromatography. After induction polychemotherapy (IPCT), patients with no progressive disease received chemoradiation (CRT) (50.4 Gy with concurrent Capecitabine and Oxaliplatin) followed by surgical resection 4 to 6 weeks after the completion of CRT. Subsequent follow-up until disease progression was remained. An exploratory analysis with Log-Rank test was performed to assess progression free survival (PFS) based on 5-FU AUC values. Results: From November 2012 to October 2018, 29 patients were retrospectively assessed: median age 63 (46-75); M/F rate 20/9; R0 resection rate of 90% in the intention-to-treat analysis. The pathological response according to CAP classification was 0, 1, 2 and 3 in 14, 58, 19.5 and 8.5%, respectively; and median number of resected lymph nodes was 11 (2-22), with lymph node infiltration (ypN1) in 14% of patients. Grade 3-4 IPCT related toxicities and grade 3 CRT related toxicities were reported in 40 and 30% of patients, respectively. Median PFS was 723 days (24 months) and median 5-FU AUC 28.5 mcg*h/ml (23-53). Median PFS for patients with 5-FU AUC ≥27 mcg*h/ml was 29 months versus 15 months in patients with 5-FU AUC < 27 mcg*h/ml (adjusted hazard ratio for disease progression 0.223; 95% CI = 0.059-0.848; p = 0.028; in a model controlled by age, sex and irinotecan dose intensity). Conclusions: 5-FU pharmacokinetic parameters achieving a target of AUC ≥ 27 mcg*h/ml seem to correlate with longer PFS in this subset of patients.

Tolerability and efficacy of modified FOLFIRINOX (mFOLFIRINOX) in patients with borderline-resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAURPC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 275-275 ◽  
Author(s):  
Marlo A. Blazer ◽  
Christina Sing-Ying Wu ◽  
Richard M. Goldberg ◽  
Gary S. Phillips ◽  
Carl Richard Schmidt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Meaningful Improvement ◽  
Best Response ◽  
Initiation Of Therapy ◽  
Grade 3

275 Background: FOLFIRINOX exhibits a meaningful improvement in outcome measures in metastatic pancreatic cancer, making it an interesting regimen for BRPC and LAURPC. However, its use remains prohibitive due to toxicity. In this study, we examine the outcomes of mFOLFIRINOX as a neoadjuvant strategy for patients with BRPC and LAURPC. Methods: This is a retrospective analysis of a prospectively maintained database of patients who received mFOLFIRINOX for BRPC or LAURPC at Ohio State University. mFOLFIRINOX is as follows: irinotecan at 165 mg/m2; oxaliplatin at 85 mg/m2; 5-fluorouracil (5FU) at 2,400 mg/m2 over 46 hours and pegfilgrastim on day 4 of each 2-week cycle. Cases were thoroughly reviewed by a multidisciplinary team prior to initiation of therapy and at each restaging scan. The primary outcomes of this analysis were resection rate and grade 3/4 (G3/4) toxicities. Results: Since 1/1/2011, 43 patients (20 BRPC; 23 LAURPC) have received mFOLFIRINOX. Patients received gemcitabine-based chemoradiation (36 Gy in 15 fractions) only if their best response was stable disease after 4 months of mFOLFIRINOX. At the time of this abstract, 39 patients are evaluable for primary outcome. Overall resection rate was 53.8% including 45% of patients with initially unresectable disease. R0 resection was achieved in 85.7% of the surgeries. See table for more results. The rate of G3/4 toxicity was remarkably low with no episodes of febrile neutropenia, G3/4 neutropenia or thrombocytopenia. Toxicities lead to dose reductions in 46% of patients. Conclusions: Neoadjuvant mFOLFIRINOX is an effective, well-tolerated regimen as part of an integrated, multimodality strategy in BRPC and LAURPC leading to high resection rates and high R0 resection frequency. [Table: see text]

Outcomes of resectable and borderline resectable pancreatic cancer patients in rural practice.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15712-e15712
Author(s):  
Sadaf Rashad ◽  
Ajaz Bulbul ◽  
Brian Jean ◽  
Sami Gholam ◽  
Emilio Paul Araujo-Mino ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Abdominal Pain ◽  
Early Stage ◽  
Neoadjuvant Treatment ◽  
Rural Practice ◽  
Rank Test ◽  
R0 Resection ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Biological Variables

e15712 Background: Accurate selection of patients based on radiological and biological variables is crucial to avoid over treatment and unnecessary R1 resection in pancreatic cancer (PC). Methods: We retrospectively investigated 73 patients diagnosed with PC treated between January 1998 to October 2015. We applied NCCN definitions for Resectable (RD), borderline resectable (BRD) and unresectable disease(URD). Logistic regression was used to identify significant indicators of R0 resection. Odds ratios were used to compare differences of overall survivability by R0 and No surgery. Fisher’s Exact Test was used for significance on all tabulated data. Wilcoxon Rank-Sum was used for the comparison of two medians and Kruskal-Wallis to compare more than two medians, and log-rank test was used to compare Kaplan-Meyer Curves. Results: Radiologically RD comprised 21% (15/73) of total cases, 80% (12/15) of these underwent R0 resection. URD comprised 79% (58/73). Patients presenting with abdominal pain were 2.5 times (Odds Ratio; p = 0.0275) more likely to be URD. The mean tumor size for R0 resectability was 2.28 cm (n = 12). The median CA 19-9 for URD was 1473 vs 162 for RD (p = 0.0124). Stage at presentation and resectability were statistically associated. (p = 0.0002): 100% of Stage 1 (n = 4) and, 27% of Stage 2, (11/41) were resectable. Twenty-three cases were identified as BRD, 21/23 received neoadjuvant chemotherapy, 47.83% had radiological PR, 28.26% had SD and 23.91% PD. There was no association between type of Neoadjuvant treatment (Chemo XRT vs Chemotherapy) and radiological response (p = 0.8798). None of the 21 BRD patients underwent surgery. Median Overall Survival for R0 resection was 22.3 months (95% CI 15.23, 36.50) vs. 5.1 who did not have surgery (95% CI 3.55, 7.57) (p = 0.0010). Conclusions: Nearly 80% patients identified as resectable on imaging underwent R0 resection. Although there were partial responses seen in BRD patients that underwent neoadjuvant treatment eventually none underwent R0 resection. Patients presenting with abdominal pain and high CA19-9 ( > 1400 U/ml) are likely to URD. Early stage and R0 resection were associated with positive outcomes.

ESPAC-5F: Four-arm, prospective, multicenter, international randomized phase II trial of immediate surgery compared with neoadjuvant gemcitabine plus capecitabine (GEMCAP) or FOLFIRINOX or chemoradiotherapy (CRT) in patients with borderline resectable pancreatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4505-4505 ◽  
Author(s):  
Paula Ghaneh ◽  
Daniel H. Palmer ◽  
Silvia Cicconi ◽  
Christopher Halloran ◽  
Eftychia Eirini Psarelli ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Recruitment Rate ◽  
Rank Test ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Immediate Surgery

4505 Background: Patients with borderline resectable pancreatic cancer have poor survival and low resection rates. Neoadjuvant therapy may improve the outcome for these patients. The aim of this trial was to determine the feasibility and efficacy of a comparison of immediate surgery versus neoadjuvant GEMCAP or FOLFIRINOX or CRT. Methods: Eligible patients with NCCN defined borderline resectable (following central review of the baseline CT scan) and biopsy proven pancreatic cancer were randomised (stratified by centre) to receive immediate surgery, or neoadjuvant therapy of either 2 cycles of GEMCAP, or 4 cycles of FOLFIRINOX or 50.4Gy capecitabine-based CRT in 28 daily fractions over 5 ½ weeks. Patients were restaged at 4-6 weeks and underwent surgical exploration if still borderline resectable. Resected patients received adjuvant therapy. Follow up was 12 months. There was quality assurance of surgery and CRT. Primary endpoints were recruitment rate and resection rate (R1/R0). Secondary endpoints included overall survival and toxicity. A target of 90 patients was set to determine feasibility and resection rates. Rates will be presented as point estimates and survival compared across treatment arms using a log-rank test. Analyses will be on an ITT basis. Results: Between August 2014 and December 2018, 90 patients were randomised with 88 included in the full analysis set (32 immediate surgery, 20 GEMCAP, 20 FOLFIRINOX, 16 CRT). Median age was 63 years, 44% were men. WHO performance status was 0 and 1 in 45% and 55% respectively. Median CA19-9 was 603 kU/L at baseline. 44 (79%) patients completed neoadjuvant therapy. Recruitment rate was 21 patients per year. Resection rate was 62% for immediate surgery and 55% for neoadjuvant therapy (p=0.668). R0 resection rate on resected patients was 15% and 23% respectively (p=0.721). One year survival rate was 40% [95% CI, 26% – 62%] for immediate surgery and 77% [95%CI, 66% - 89%] for neoadjuvant therapy. Log-rank analysis showed an HR=0.27 [95% CI, 0.13 – 0.55]; χ2 (1) = 14.91, P<0.001. 9 out of the 51 neoadjuvant patients included in the safety set reported 12 serious adverse events of grade 3 or above. Conclusions: There was no difference in resection rate between arms, however neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Clinical trial information: 89500674 .

scholarly journals Added Value of Radiotherapy Following Neoadjuvant FOLFIRINOX for Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Quisette P. Janssen ◽  
Jacob L. van Dam ◽  
Isabelle G. Kivits ◽  
Marc G. Besselink ◽  
Casper H. J. van Eijck ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Added Value ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

Abstract Background The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. Methods A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. Results We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. Conclusions In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.

Multimodality therapy for borderline resectable pancreatic cancer: A single-institution experience.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 280-280
Author(s):  
Jose Mario Pimiento ◽  
Tai Hutchinson ◽  
Jill M. Weber ◽  
Manish R. Patel ◽  
Pamela Joy Hodul ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Multimodality Therapy ◽  
Cancer Center ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

280 Background: Multimodality therapy has been advocated for borderline resectable pancreatic cancer (BRCP); however, specific regimens vary widely by institution. Outcomes of these interventions need to be examined to inform future investigation of the optimal therapy for these patients. This study represents the experience of multimodality therapy for BRPC at an NCI designated cancer center. Methods: We identified all patients (pts) with operable pancreatic ductal adenocarcinoma (PDA) from 2006 to 2011. Patients were divided into two groups: resectable group and BRPC group as per the NCCN and AHPBA consensus guidelines. Primary outcomes were resection rate, microscopic negative margin (R0) resection rate, overall survival (OS), and disease free survival (DFS). Fisher's exact and chi-square were used for group comparison while Kaplan-Meier estimates was used for survival analysis. Results: 160pts were identified with operable PDA. 100 (63%) pts had resectable tumors, and 60 (37%) pts had borderline resectable tumors. Neoadjuvant therapy (NT) was administered to 0% in the group with resectable tumors, and 100% in the group with borderline resectable tumors. The resection rate was 100% in pts with resectable tumors and 58% in pts with borderline resectable tumors. R0 resection rates were 80% in the resectable tumors and 97% in the borderline resectable tumors following NT. Perioperative mortality was <1% (1/125) for resectable tumors and 0% in borderline resectable tumors. Median OS was 22.6 months (m) for pts that had resectable tumors and 13.9m for all pts with borderline resectable tumors (p=0.017); however, the median OS for resected pts with borderline resectable tumors was 21.5m (p=0.6). Improved DFS was seen in patients with resectable tumors when compared with resected borderline resectable tumors (15 vs. 9.5m; p=0.04). Conclusions: Multimodality therapy leads to high rates of R0 resections in borderline resectable pancreatic cancer; however 42% of patients progressed during NT. The overall survival for patients with resected borderline resectable pancreatic cancer following NT is similar to patients who undergo resection for resectable pancreatic cancer.

Accelerated fraction radiotherapy with concomitant capecitabine as neoadjuvant therapy of borderline resectable pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 329-329 ◽  
Author(s):  
Samhita Chakraborty ◽  
Todd W. Bauer ◽  
Monica M Morris ◽  
Erin Yarde ◽  
J Thomas Parsons ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Palliative Therapy ◽  
External Beam Radiation ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Beam Radiation ◽  
Early Stage Disease ◽  
Borderline Resectable Pancreatic Cancer ◽  
Grade 3

329 Background: Surgical therapy remains the only curative modality for pancreatic cancer, though survival remains quite poor even for patients with resected early stage disease. Better (neo) adjuvant therapies are needed to improve resectability rates for patients with borderline resectable pancreatic cancer and to prevent recurrence following resection. We undertook this pilot study to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in such patients. Methods: Eligible patients have histologically confirmed borderline resectable adenocarcinoma of the pancreas as defined by the MD Anderson categories of vascular involvement, indeterminate metastatic disease, borderline performance status; normal organ function; and no prior therapy for pancreatic cancer. Radiation is given as external beam radiation therapy to a dose of 50 Gy delivered in 20, 2.5 Gy fractions Mon-Fri using IMRT. If insurance denied IMRT, 3D conformal techniques with daily image guidance is permitted. Capecitabine is delivered as 825mg/m2 BID on radiation days. The primary outcome is to determine the frequency of treatment-related adverse events (AE). Planned enrollment is 40 pts. Results: 10 pts have enrolled to date. 8/10 received IMRT. This regimen has been exceedingly tolerable. Lymphopenia is the most common AE (n=10), grade 3-4 n=6. Other common toxicities were hyponatremia (n=6), fatigue (n=5). Grade 3 AE occurred in 8 pts, grade 4 in 3 patients. One pt had hemorrhage from a radiation induced gastric ulcer complicated by an MI. 5/10 pts had stable disease and were resected and 4/5 had an R0 resection. In the remaining 5/10 patients, disease progressed outside the pancreas and they are receiving palliative therapy. Conclusions: The combination of AFRT and capecitabine was well tolerated. Xenograft models derived from these patients’ tumors are being used to study molecular mechanisms of treatment resistance that could be targeted in a follow up phase II study building on this platform.

Prognostic factors of pancreatic neck cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 355-355
Author(s):  
Seiko Hirono ◽  
Masaji Tani ◽  
Manabu Kawai ◽  
Ken-Ichi Okada ◽  
Motoki Miyazawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Neck Cancer ◽  
Celiac Trunk ◽  
Ct Imaging ◽  
R0 Resection ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Pancreatic Neck

355 Background: Pancreatic neck cancer is surrounded by common hepatic artery (CHA), gastroduodenal artery (GDA) and portal vein (PV), and easily invades nerve plexus around main arteries, such as CHA, celiac trunk, and superior mesenteric artery (SMA). Therefore, the resectablity of pancreatic neck cancer is low, and the biological behaviors have been unclear. In this study, we reviewed 59 resected pancreatic neck cancer cases to identify the prognostic factors. Methods: From 2000 to 2012, 305 patients with pancreatic cancer underwent surgical resection, and in 59 patients (19%) among them with pancreatic neck cancer, 49 patients underwent pancreatoduodenectomy, 5 subtotal pancreatectomy, 4 distal pancreatectomy with en-bloc celiac axis, and 1 total pancreatectomy. We defined borderline resectable pancreatic cancer as tumor abutted CHA, celiac trunk, or SMA, and classified radiographic types of PV invasion into A (normal), B (unilateral), C (bilateral), or D (complete obstruction) by CT imaging. We analyzed retrospectively clinicopathological characteristics and prognostic factors for pancreatic neck cancer. Results: Pancreatic neck cancer was smaller than other located pancreatic cancer (21.1±7.0 vs. 32.0±13.5 mm, P<0.01), and the rate of pathological PV invasion was higher in pancreatic neck cancer (36 vs. 20%, P=0.01). In patients with pancreatic neck cancer, pathological PV invasion was observed in 0% of type A (0/9), 14% of type B (3/22), 48% of type C (10/21), and 86% of type D (6/7), and 37 patients (63%) had lymph node metastasis. In 32 patients with borderline resectable pancreatic neck cancer, neoadjuvant chemo(radiation)therapy (NAC) reduced the R1 rates (P=0.04) Pathological PV invasion, tub2/3 and lymph node ratio >0.1 were independent poor prognostic factors for pancreatic neck cancer (P<0.01, P=0.03, and P=0.03, odds ratio; 7.1, 2.8, and 3.1, respectively). Conclusions: Pancreatic neck cancer often had PV invasion even if CT imaging showed unilateral abutment, indicating that combined PV resection may be necessary for R0 resection of pancreatic neck cancer with radiological PV abutment. NAC may improve R0 resection rates and postoperative survival for pancreatic neck cancer.

Preliminary safety data from a randomized multicenter phase Ib/II study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4125-4125 ◽  
Author(s):  
Matthew H. G. Katz ◽  
Gauri R. Varadhachary ◽  
Todd W. Bauer ◽  
Nicolas Acquavella ◽  
Nipun B. Merchant ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Treatment ◽  
Safety Data ◽  
Neoadjuvant Chemoradiation ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Resectable Disease ◽  
Post Surgery ◽  
Grade 3 ◽  
To Receive

4125 Background: Pancreatic cancer (PC) is a challenging target for immunotherapy.Tumor-infiltrating lymphocytes (TILs) do not reach the PC cells in significant numbers due to the presence of stroma and a suppressive microenvironment. Neoadjuvant chemoradiation (CRT) can increase the presence of TILs in the PC microenvironment. We hypothesized that combination of CRT and pembrolizumab can lead to further increase in TILs and their activation. Methods: Patients with resectable or borderline resectable PC have been randomized 2:1 to the investigational treatment (Arm A) to receive pembrolizumab 200mg IV every 3 weeks on days 1, 22, and 43 during concurrent CRT with capecitabine (825 mg/m2 orally twice daily, Monday-Friday, on days of radiation only) and radiation (50.4 Gy in 28 fractions over 28 days) or Arm B to receive only concurrent CRT with capecitabine. Restaging CT scan or MRI is performed at 4-6 weeks after completion of neoadjuvant treatment, and patients with resectable disease will undergo surgical resection. Here we report the preliminary safety data based on 22 enrolled patients. Results: As of February 3-2017,22 patients have been enrolled (14 Arm A and 8 Arm B). 50% of the patients had resectable disease (7 arm A; 4 arm B) and the other 50% had borderline resectable disease (7 Arm A; 4 arm B). Post-neoadjuvant therapy, 6 patients had unresectable disease (3 on each arm), and 14 patients underwent surgery (10 arm A and 4 arm B). There were 7 grade 3 treatment-related toxicities in Arm A (5 patients): 2 grade 3 diarrhea attributed to CRT; 4 grade 3 lymphopenias attributed to pembrolizumab, CRT or the combination; and one patient had elevated alkaline phosphatase probably related to the combination that met the definition of DLT and resolved after holding the treatment and receiving steroids. There was only one grade 3 toxicity on Arm B: lymphopenia attributed to CRT. No grade 4 toxicities have been reported on either arm. There were no major surgical complications reported within 30 days post-surgery. Conclusions: The combination of CRT and pembrolizuamb is safe based on the presented data. Clinical trial information: NCT02305186.

Phase II trial of neoadjuvant S-1 and concurrent radiotherapy for borderline resectable pancreatic cancer: Interim results of JASPAC05.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4107-4107 ◽  
Author(s):  
Shinichiro Takahashi ◽  
Izumi Ohno ◽  
Masafumi Ikeda ◽  
Masaru Konishi ◽  
Tatsushi Kobayashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Primary Endpoint ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Concurrent Radiotherapy

4107 Background: Borderline resectable pancreatic cancer (BRPC) has a high probability of a positive surgical margin and poor prognosis because the tumor interacts with surrounding arteries or veins. Chemoradiotherapy (CRT) with S-1 has shown favorable activity in locally advanced pancreatic cancer. This study was designed to assess S-1 and concurrent radiotherapy in a neoadjuvant setting to determine whether it increases R0 resection rate for BRPC. Methods: This was a multicenter, single-arm phase II study. Patients with BRPC received S-1 (40 mg/m2 BID) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery if they fulfilled any of the following: (1) bilateral impingement of superior mesenteric vein or portal vein; (2) tumor contact with superior mesenteric artery ≤180°; or (3) tumor contact with common hepatic artery or celiac axis ≤180°. Primary endpoint was R0 resection rate in BRPC confirmed by central review. At least 40 patients were required, with one-sided α = 0.05 and β = 0.05, with an expected and a threshold values for primary endpoint of 30% and 10%. Results: Fifty-two patients were eligible between December 2012 and May 2016. CRT was completed in 50 patients (96%) and was safe, with mostly grade 1 or 2 adverse events. Protocol treatment was withdrawn before surgery in 12 patients because of progressive disease diagnosed by computed tomography, and in one because of treatment refusal. Ten patients received exploratory laparotomy, or palliative/noncurative resection. In the rest of 29, R0 resection was conducted in 27, and R1 and RX in 1 patient each. This gave an R0 resection rate of 52% in all 52 eligible patients. In the 41 cases of BRPC confirmed by central review, R0 was confirmed in 26 (63%). Destruction of > 50% of tumor cells was confirmed pathologically in 10 (32%). Postoperative grade III/IV adverse events according to Clavien–Dindo classification were observed in 6 (15%). Conclusions: S-1 and concurrent radiotherapy were well tolerated and found to be effective in BRPC. A randomized controlled trial comparing neoadjuvant CRT and chemotherapy, including gemcitabine+nab-paclitaxel, for BRPC is under planning. Clinical trial information: NCT02459652.

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