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
1988 - Molecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix
Presenter: Semir Vranic
Session: Poster Display session 2
Resources:
Abstract
2672 - Changes in clinico-pathological characteristics of vulvar cancer in Japan: increasing oldest-old, stage-shifting, and decreasing cohort-level survival
Presenter: Shin Nishio
Session: Poster Display session 2
Resources:
Abstract
4306 - Tumor Treating Fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer: Phase 3 INNOVATE-3/ENGOT-ov50 study
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
5136 - Randomized, phase 1b/2 study of M6620 + avelumab + carboplatin vs standard care (sc) in patients (pts) with platinum-sensitive poly (ADP-ribose) polymerase inhibitor-(PARPi)-resistant ovarian cancer
Presenter: Susana Banerjee
Session: Poster Display session 2
Resources:
Abstract
2296 - An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION
Presenter: Jung-Yun Lee
Session: Poster Display session 2
Resources:
Abstract
2732 - A phase 2 study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer
Presenter: Ana Oaknin
Session: Poster Display session 2
Resources:
Abstract
4404 - ENGOT-EN9/LEAP-001: a phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer
Presenter: Christian Marth
Session: Poster Display session 2
Resources:
Abstract
4564 - Phase 1/2 trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
4933 - Updated data of Epitopes-HPV02 trial and external validation of efficacy of DCF in prospective Epitopes-HPV01 study in advanced anal squamous cell carcinoma. Pooled analysis of 115 patients
Presenter: Stefano Kim
Session: Poster Display session 2
Resources:
Abstract
2301 - Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent chemoradiotherapy (CRT) in anal cancer (PLATO-ACT5)
Presenter: Alexandra Gilbert
Session: Poster Display session 2
Resources:
Abstract