Predictors of toxicity in treating patients with neuroblastoma by radiolabeled metaiodobenzylguanidine

Abstract

We searched for methods that would enable prescriptions of the maximum tolerable doses of iodine-131 metaiodobenzylguanidine (MIBG) and iodine-125 MIBG in the treatment of patients with neuroblastoma. We correlated doses, defined in different ways, with subsequent platelet levels in treated patients to determine accurate predictors of the most frequent toxicity, thrombocytopenia. Nine patients with neuroblastoma were given 131 I-MIBG (4.9–8.1 GBq or 132–220 mCi) and ten were given 125 I-MIBG (8.3-30.0 GBq or 224–809 mCi) as initial treatments. These therapies were sufficiently varied that correlations could be made between indices of the doses and the subsequent toxicity as reflected in circulating platelet levels. Predictors of toxicity were: whole-body absorbed dose of radiation (cGy) calculated from pretherapy tracer doses of 131 I-MIBG; GBq/kg of body weight; and GBq/m 2 of body surface area. Toxicity was recorded as the nadir of the platelet level and platelet/pretherapeutic level (platelet ratio). For treatments with 131 I-MIBG, the highest correlation was obtained between cGy and the logo 10 -transformed platelet ratio ( r =−0.86), but comparison of GBq/m2 and the platelet nadir ( r =−0.76) or the platelet ratio ( r =−0.74) or the log 10 − transformed platelet ratio ( r =−0.73) gave comparable and statistically significant results. For treatments with 125 I-MIBG, significant correlations were obtained between GBq/m 2 and the platelet ratio ( r =−0.81) or GBq/kg and the log 10 − -transformed platelet ratio; the correlation between cGy and any toxicity index was low. Per administered GBq, 131 I-MIBG was 2.6 times more potent than 125 I-MIBG in causing a platelet ratio of 0.1. Thus, in predicting toxicity, therapeutic doses of 131 I-MIBG expressed as GBq/m 2 performed satisfactorily and almost as well as whole-body cGy, and treatment doses of 125 I-MIBG expressed as GBq/m 2 or GBq/kg performed satisfactorily and much better than whole-body cGy.