Peptide Receptor Radionuclide Therapy and clinical associations with renal and hematological toxicities and survival in patients with neuroendocrine tumors: an analysis from two U.S. medical centers.

PURPOSE

Renal and hematological toxicity are side effects and dose-limiting factors of Peptide Receptor Radionuclide Therapy (PRRT). We aimed to assess the changes in renal and hematological function and associations with survival in neuroendocrine tumor (NET) patients treated with PRRT.

METHODS

A retrospective cohort of 448 NET patients treated with either Lu-DOTATATE or Y-DOTATOC were followed for changes of renal and hematological function. Renal function was assessed by monitoring changes in serum creatinine, blood urea nitrogen and estimated glomerular filtration rate. Hematological function was determined by examining changes in white blood cell counts (WBC), platelet counts, and hemoglobin levels over time. Piecewise linear mixed effect models were applied to model the longitudinal repeated measurements of renal and hematological function. Overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazard regressions.

RESULTS

Of the 448 PRRT treated patients, 335 received Lu-DOTATATE (74.78%) and 113 were treated with Y-DOTATOC (25.22%). Comparing patients treated with Lu-DOTATATE to those treated with Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with Lu-DOTATATE prior to and during PRRT treatment (WBC: estimate, -0.10, 95% CI, -0.15 to -0.05; P < 0.001; platelet count: estimate, -2.53, 95% CI, -3.83 to -1.24; P < 0.001), and no significant recovery was observed in hematological function post PRRT. Individuals who received Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28-0.79, P = 0.004) compared with Y-DOTATOC, but there was no difference in OS.

CONCLUSION

There was no significant renal, but minor hematological toxicity, in patients treated with Lu-DOTATATE compared with Y-DOTATOC. Compared to Y-DOTATOC, Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT.