scholarly journals Phase II Study of Bevacizumab With Concurrent Capecitabine and Radiation Followed by Maintenance Gemcitabine and Bevacizumab for Locally Advanced Pancreatic Cancer: Radiation Therapy Oncology Group RTOG 0411

2009 ◽  
Vol 27 (25) ◽  
pp. 4096-4102 ◽  
Author(s):  
Christopher H. Crane ◽  
Kathryn Winter ◽  
William F. Regine ◽  
Howard Safran ◽  
Tyvin A. Rich ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Locally Advanced ◽  
Radiation Therapy Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Primary Objective ◽  
Gastrointestinal Toxicity ◽  
Locally Advanced Pancreatic Cancer ◽  
Oncology Group ◽  
Grade 3

PurposeThe primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR).Patients and MethodsPatients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m2orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m2weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA).ResultsBetween January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05).ConclusionThe addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials.

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.

Prognostic impact of chemoradiation-related lymphopenia in patients with locally advanced pancreatic cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 439-439
Author(s):  
Daniel W Kim ◽  
Grace Lee ◽  
Colin D. Weekes ◽  
David P. Ryan ◽  
Aparna Raj Parikh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cox Model ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Pancreatic Head ◽  
Locally Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Entire Cohort ◽  
Grade 3

439 Background: Chemoradiation (CRT) induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. The objective of this study was to evaluate the prognostic impact of lymphopenia in patients with nonmetastatic, unresectable pancreatic ductal adenocarcinoma (PDAC) treated by neoadjuvant FOLFIRINOX (5-fluorouracil [5FU]/leucovorin/irinotecan/oxaliplatin) followed by CRT. We hypothesized that severe lymphopenia would correlate with worse survival. Methods: The inclusion criteria for this single-institution retrospective study were: 1) biopsy-proven diagnosis of unresectable PDAC, 2) absence of distant metastasis, 3) receipt of neoadjuvant FOLFIRINOX followed by CRT, and 4) absolute lymphocyte count (ALC) available prior to and two months after initiating CRT. In general, CRT consisted of 5FU or capecitabine and RT with 58.8 Gy over 28 fractions. Lymphopenia was graded according to CTCAE v5.0. The primary variable of interest was lymphopenia at two months, dichotomized by ALC of < 0.5/μl (Grade 3 lymphopenia). The primary endpoint was overall survival (OS). Cox modeling and Kaplan-Meier methods were used to perform survival analyses. Results: A total of 138 patients were identified. Median follow-up for the entire cohort was 16 months. Median age was 65. Fifty-six percent were female, 86% were Caucasian, and 97% had ECOG ≤1. Median tumor size was 3.8 cm. Tumor location was pancreatic head in 63%, body in 22%, tail in 8%, and neck in 7%. Median baseline ALC for the entire cohort was 1.5 k/ul. Two months after initiating CRT, 106 (77%) had severe (Grade 3 or worse) lymphopenia. While there were no significant differences in baseline patient or disease characteristics, patients with severe lymphopenia received higher doses of RT with longer duration of treatment compared to those without severe lymphopenia. On multivariable Cox model, severe lymphopenia at two months was significantly associated with increased hazards of death (HR = 4.00 [95% CI 2.03-7.89], p < 0.001). Greater number of neoadjuvant FOLFIRINOX cycles received prior to CRT was associated with lower hazards of death (HR = 0.84 [95% CI 0.77-0.92], p < 0.001). The 12-month OS was 73% vs. 90% in the cohort with vs. without severe lymphopenia, respectively (log-rank p < 0.001). Conclusions: Treatment-related lymphopenia is common and severe lymphopenia may be a prognostic marker of poorer survival in locally advanced pancreatic cancer. Closer observation in high-risk patients and minimization of RT dose and duration are potential approaches to mitigating CRT-related lymphopenia. Our findings also suggest an important role of the host immunity in pancreatic cancer outcomes, supporting the ongoing efforts of immunotherapy trials in pancreatic cancer.

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