Acute Changes in Blood Pressure in Patients With Neuroblastoma Treated With 131IMetaiodobenzylguanidine (MIBG)

Neuroblastoma is an embryonal tumor derived from the peripheral sympathetic nervous system. Metastatic disease is present at diagnosis in half of the cases. Despite improvement in outcome with intensification of therapy and treatment of minimal residual disease, 15%of patients with high-risk neuroblastoma have disease that is refractory to induction chemotherapy, and more than 50% of patients who achieve initial remission ultimately relapse and die as a result of their disease [1]. As a tumor derived from the sympathetic nervous system, neuroblastoma cells typically express the norepinephrine transporter. This allows for the active intracellular uptake of radiolabeled metaiodobenzylguanidine (MIBG). MIBG is a guanethidine derivative and analogue of norepinephrine with specific affinity for neural crest tissues.When labeled with iodine-131 (I-MIBG), MIBG serves as a targeted radiotherapy for children with neuroblastoma, with response rates varying from 25% to 40% [2]. In the largest phase II clinical trial of 164 patients with relapsed disease treated with I-MIBG, the response rate for all patients was 36% [3]. I-MIBG has predominantly been used as a single agent in relapsed disease. However, I-MIBG is increasingly being used as a form of treatment earlier in the course of disease or combined with other agents. With this expanding role in therapy for neuroblastoma, it is essential to develop a greater understanding of the side effects of I-MIBG in these patients. Patients with neuroblastoma may present with hypertension in approximately 10% of cases [4]. However, the specific effect of I-MIBG administrations on blood pressure in neuroblastoma patients has not been extensively investigated. Elevated blood pressure during and following I-MIBG administration is of particular interest since I-MIBG is a norepinephrine analogue that has the potential to mimic the physiologic effects of norepinephrine [5]. The few reports on hypertension following I-MIBG therapy have shown varying results. A phase I/II study of I-MIBG in neuroblastoma found that 3 of 25 patients developed asymptomatic transient changes in blood pressure between 2 and 4 hours after administration. The changes observed were variable with one patient becoming hypertensive and two hypotensive. No patients required pharmacologic intervention [6]. Another study reported that the majority of infusions were uncomplicated, with blood pressure changes that were not predictable or clinically relevant. However, this group reported four significant adverse events related to hypertension that occurred during or within 1 day after IMIBG administration [7]. We report here a systematic analysis of the effects of I-MIBG therapy on blood pressure in patients with neuroblastoma. We examined the relationship between changes in blood pressure during and after treatment with I-MIBG and possible risk factors, including both patient specific variables and characteristics of the infusion. Background. Iodine-131-metaiodobenzylguanidine (I-MIBG) provides targeted radiotherapy for children with neuroblastoma. The aim of our study was to evaluate systematically the acute effects of I-MIBG on blood pressure in patients with neuroblastoma and to identify possible predictors of hypertension. Procedure. We conducted a retrospective chart review of neuroblastoma patients who were treated with I-MIBG between January 1, 1999 and June 1, 2012 at the University of California, San Francisco. Clinical data for 172 patients with neuroblastoma, receiving 218 administrations of I-MIBG, were collected. The primary endpoint was development of systolic blood pressure above the 95th percentile for age. Logistic regression with generalized estimating equations to account for multiple administrations in some subjects was used to identify bivariate andmultivariate predictors of hypertension.Results. Of the 218 administrations of I-MIBG, 112 (51.3%) were associated with at least one episode of systolic hypertension during or after the I-MIBG infusion. Themajority of these acute elevations in blood pressure resolved within 48hours of the infusion. Only six administrations in five patients required nifedipine administration to lower blood pressure. Younger age (P1⁄40.012), lower eGFR (P1⁄40.047), and elevated blood pressure measurements immediately before infusion began (P1⁄40.010) were all independently associated with risk of treatment-associated hypertension. Conclusions. Acute elevations in blood pressure are common after therapeutic doses of I-MIBG. Elevations in blood pressure typically occur only within the first 48hours after I-MIBG administration. Blood pressure monitoring during this period of risk is recommended. Pediatr Blood Cancer 2013. # 2013 Wiley Periodicals, Inc.