Abstract 4725
Background
Metastatic pancreatic neuroendocrine tumors (PNET) are generally not curable; however, some patients may have prolonged survival. Until recently, metastatic PNET were primarily managed with somatostatin-analogs. New developments demonstrating therapeutic value of temozolomide (TMZ) in these patients resulted in its off-label use in National Comprehensive Cancer Network guidelines. Given alone, or in combination with other therapies, TMZ is associated with improved clinical outcomes. However, serious hematologic adverse events (AEs) like agranulocytosis, lymphopenia and aplastic anemia are not uncommon. At the University of Kansas Cancer Center (KUCC), 3 patients with history of TMZ-treated metastatic PNET developed hematologic malignancies. The purpose of this study is to determine the incidence of secondary malignancies (SM) in this patient population.
Methods
A systematic review of all known clinical trials, case reports, and other relevant literature regarding PNET and TMZ published before September 2017 was conducted using PubMed, Embase, Cochrane Library, and the FDA Adverse Event Reporting System (FAERS).
Results
We analyzed 38 publications and 8,215 cases reported from FAERS. AEs ranged from agranulocytosis to myelodysplastic syndrome. No publications reported any SM. The 3 patients identified at KUCC are as follows: 1) 29-year-old female with TMZ-treated metastatic PNET developed acute myeloid leukemia with cytogenetics consistent with therapy-related leukemia. 2) 80-year-old male with TMZ-treated metastatic PNET developed diffuse large B-cell lymphoma. 3) 12-year-old male with TMZ-treated metastatic PNET developed high-grade T-cell lymphoblastic lymphoma. All these patients succumbed to their hematologic malignancies, and not the underlying PNET.
Conclusions
Although we observed 3 cases at KUCC, this retrospective review did not find any cases of SM in TMZ-treated metastatic PNET. We believe that the leukemogenic potential of TMZ is underreported. It is important for treatment guidelines to address this risk in the decision to pursue TMZ treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5472 - Early response evaluation and CEA response in patients treated in a Danish randomized study comparing trifluridine/tipiracil (TAS-102) with or without bevazicumab in patients with chemorefractory metastatic colorectal cancer (mCRC)
Presenter: Camilla Qvortrup
Session: Poster Display session 2
Resources:
Abstract
2037 - Updated survival analysis of the randomized phase III trial comparing S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer (SALTO) by the Dutch Colorectal Cancer Group.
Presenter: Johannes Kwakman
Session: Poster Display session 2
Resources:
Abstract
3053 - JFMC51-1702-C7: Phase II study investigating efficacy and safety of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients (pts) with metastatic colorectal cancer (mCRC) refractory or intolerant to standard chemotherapies.
Presenter: Keisuke Kazama
Session: Poster Display session 2
Resources:
Abstract
3183 - Bevacizumab plus trifluridine/tipiracil in elderly patients with previously untreated metastatic colorectal cancer (KSCC 1602): A single-arm, Phase 2 study
Presenter: Akitaka Makiyama
Session: Poster Display session 2
Resources:
Abstract
3233 - Biweekly TAS-102 and Bevacizumab as a Third-Line Chemotherapy for metastatic colorectal cancer: A Phase II Multicenter Clinical Trial (TAS-CC4 study)
Presenter: Yoichiro Yoshida
Session: Poster Display session 2
Resources:
Abstract
5907 - Liquid biopsy concordance based on clonality and timing of testing in patients with metastatic colorectal cancer
Presenter: Pashtoon Kasi
Session: Poster Display session 2
Resources:
Abstract
1866 - Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer
Presenter: Emilie Moati
Session: Poster Display session 2
Resources:
Abstract
2312 - High Circulating miR-1247 is a marker for poor prognosis in patients with metastatic colorectal cancer treated with chemotherapy and cetuximab
Presenter: Jakob Schou
Session: Poster Display session 2
Resources:
Abstract
5602 - Clinical relevance of circulating tumor (ct)DNA genotyping for first line cetuximab-based treatment monitoring in metastatic colorectal cancer (mCRC): a prospective multicentric study
Presenter: JOANA Vidal Barrull
Session: Poster Display session 2
Resources:
Abstract
3182 - Clonal hematopoiesis mutations in plasma cfDNA RAS/BRAF genotyping of metastatic colorectal cancer
Presenter: Beili Wang
Session: Poster Display session 2
Resources:
Abstract