Shirley Mallette

131-I-metaiodobenzylguanidine treatment in patients with refractory advanced neuroblastoma

Fourteen patients with refractory advanced neuroblastoma were treated with 131-I-metaiodobenzylguanidine (131–1-MIBG); all had evidence of progressive disease or recurrent disease following combination chemotherapy. One patient without gross evidence of disease, following surgical resection of recurrent neuroblastoma before therapy with 131-I-MIBG, remains healthy without regrowth of tumor 3.5 years later. Two other patients had minor responses, and one had a mixed response. Two patients remain alive 1,212 and 1,926 days following the initial 131-I-MIBG treatment; the remaining 12 patients died of progressive disease. Moderate myelosuppression was the most notable toxicity observed; mild nausea and vomiting and transient mild liver enzyme elevation were also encountered. Treatment with 131-I-MIBG produced antineoplastic activity in patients with neuroblastoma and was well tolerated. To evaluate dose escalation, alternative dosage schedules, and alternative MIBG-radioconjugates, additional trials of radiolabeled MIBG are indicated.

Toxicity from treatment of neuroblastoma with 131I-meta-iodobenzylguanidine

Toxic effects from 131I-meta-iodobenzylguanidine (131I-MIBG) treatments of neuroblastoma in six patients were recorded. The toxicity was largely confined to the hematologic system where circulating leukocytes and platelets regularly declined after each dose of 131I-MIBG; the values reached nadirs between three and seven weeks and recovered slowly over subsequent weeks. Prior bone marrow transplantation and infiltration of bone marrow by neuroblastoma appeared to make the hematologic system more vulnerable to the radiation. Dosimetry revealed greater absorbed radiation by the whole body than by the blood and bone marrow. These observations are explained by a relatively rapid exit of 131I-MIBG from the blood to other tissues (but not to the bone marrow). Since treatment of an aggressive and lethal tumor such as neuroblastoma should be pushed to a degree of toxicity, careful dosimetry in each case will be necessary as a guide to reach the point of maximally tolerable toxicity.