Long-term hematologic toxicity of 177Lu-octreotate-capecitabine-temozolomide therapy of GEPNET

in Endocrine-Related Cancer
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  • 1 M Kesavan, Oncology, The University of Western Australia Faculty of Medicine Dentistry and Health Sciences, Perth, Australia
  • 2 P Grover, Department of Oncology, Fiona Stanley Hospital, Perth, Australia
  • 3 W Lam, Department of Oncology, Fiona Stanley Hospital, Perth, Australia
  • 4 P Claringbold, Oncology, The University of Western Australia Faculty of Medicine Dentistry and Health Sciences, Perth, Australia
  • 5 J Turner, Oncology, The University of Western Australia Faculty of Medicine Dentistry and Health Sciences, Perth, Australia

Correspondence: Murali Kesavan, Email: murali.kesavan@research.uwa.edu.au
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Thirty-seven patients with advanced gastroenteropancreatic neuroendocrine tumors (GEPNETs) were treated on a prospective phase II single-center study with 4 cycles of 7.8 GBq 177Lu-octreotate combined with capecitabine and temozolomide chemotherapy (CAPTEM). Each 8-week cycle combined radiopeptide therapy with 14 days of capecitabine (1500 mg/m2) and 5 days of temozolomide (200 mg/m2). The incidence of grade ≥3 hematologic toxicity was analysed. We found that at a median follow-up of 7-years (range 1-10), 6 (16%) patients developed persistent hematologic toxicity (PHT, defined as sustained grade ≥3 hematologic toxicity beyond 36-months follow up) and 3 (8%) developed MDS/AL with a median time-to-event of 46 and 34-months respectively. Estimated cumulative incidence of MDS/AL was 11% (95% CI: 3.45 to 24.01). Development of PHT was the only significant risk factor for secondary (RR, 16; 95% CI: 2.53 to 99.55; p<0.001). The median PFS was 48 months (95% CI: 40.80-55.20) and median OS was 86 months (95% CI: 56.90-115.13). 21 deaths were recorded, including 13 (62%) due to progressive disease and all 3 (14%) patients with MDS/AL. We conclude that 177Lu-octreotate CAPTEM therapy for GEPNETs is associated with a risk of long-term hematologic toxicity. The rising cumulative incidence of MDS/AL >10% mandates for the long-term monitoring of treated patients. However, time to onset is unpredictable and incidence does not correlate with conventional baseline risk factors. Novel methods are required for stratification of prospective patients based on genetic risk.

 

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