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Targeted radiotherapy for chemotherapy resistant neuroblastoma with I-131 metaiodobenzylguanidine (MIBG) (Targeted radiotherapy for chemotherapy resistant neuroblastoma with I-131 metaiodobenzylguanidine (MIBG))

Targeted radiotherapy for chemotherapy resistant neuroblastoma with I-131 metaiodobenzylguanidine (MIBG) (Targeted radiotherapy for chemotherapy resistant neuroblastoma with I-131 MIBG)

63

Neuroblastoma

Interventional, single arm study, open (masking not used), no treatment control, parallel assignment, treatment purpose

26 deaths 1) 20 cases of exacerbation of the disease 2) Death due to continuous treatment complications (1 case of Pseudomonas aeruginosa, 1 case of Aspergillus pneumonia, 2 cases of respiratory failure, 1 case of renal failure, 1 case of bone marrow transplant-related complications)

I-131 MIBG was administered to 63 patients (male: female = 36: 27; average 9 years old; 23 cases of newly diagnosed neuroblastoma, 23 cases of 1st recurrence, 15 cases of the 2nd recurrence, 2 cases of the 3rd recurrence) [I-131 MIBG dose; 361mCi (range 90-660mCi), 15mCi/kg (range 3-18 mCi/kg)] were performed. The number of administrations was 55 in 1 time, 6 in 2 times, and 2 in 3 times. The treatments following I-131 MIBG treatment were autologous transplantation in 21, autologous transplantation in 21 cases, external irradiation in 24 cases, and 13-cis-retinoic acid in 11 cases. Main evaluation items: Evaluation of the antitumor effect 1) Overall effect valuation by RECIST and MIBG scintigraphy after intensive treatment: CR (n=16, 25%), PR (n=9, 14%), SD (n=19, 30%), PD (n=13, 21%), NE (n=6, 10%). 2) During follow-up, 20 patients had an exacerbation of the disease, and 6 had deaths due to continuous therapy complications. The 5-year estimated survival rate after initial treatment of I-131 MIBG calculated using the Kaplan-Meier method was 51% for all patients, 65% for initial patients, and 45% for recurrent patients. For patients with CR to induction therapy as demonstrated by diagnostic I-123 MIBG scintigraphy, 5-year estimated survival rate was 83% (n=6) in newly diagnosed patients and 66% (n=10) in recurrent patients, respectively. The 5-year estimated survival rate of all patients after the first diagnosis was 72%. Secondary evaluation items: Evaluation of adverse events 1) Sixty-five adverse events, excluding decreased bone marrow function from before treatment, were observed as acute side effects observed after I-131 MIBG treatment in the radiation control area was exited. Radiation sickness, salivary gland inflammation, abdominal pain, headache, and nose bleeding were observed. The Grade was less than 3. 2) Decreased bone marrow function: Red blood cell transfusion, platelet transfusion, and G-CSF infusion were performed in 19 cases, 18 cases, and 18 cases, respectively, after treatment with I-131 MIBG (survey data were not collected in 18 cases). 3) Side effects other than decreased bone marrow function: fatigue, glucose intolerance, creatinine increased, AST elevation, ALT elevation, T-Bil elevation, pain, fever, purpura, epistaxis, mucositis oral, dry mouth, dyspepsia, diarrhea, hypothyroidism, pneumonitis, heart failure, pleural effusion, and decreased bone density were reported. 4) Long-term side effects: Of the 24 patients, 3 patients had renal dysfunction, and 7 patients had thyroid dysfunction. No secondary carcinogenesis was reported.

Sixty-three neuroblastoma patients received I-131 MIBG treatment (23 cases of newly diagnosed and 46 cases of recurrent neuroblastoma). In the study period, there were 20 deaths due to exacerbation of the disease and 6 deaths from continuous treatment complications. The 5-year estimated survival rate after the initial treatment of I-131 MIBG was 65% in the newly diagnosed patients and 45% in the recurrent patient. The safe administration of I-131 MIBG for neuroblastoma was possible.

Oct. 05, 2020

No

No

https://jrct.niph.go.jp/latest-detail/jRCTs041180041

Kinuya Seigo

Kanazawa Universtiy

Takaramachi 13-1, Kanazawa-shi, Ishikawa

kinuya@med.kanazawa-u.ac.jp

Wakabayashi Hiroshi

Kanazawa University Hospital

Takaramachi 13-1, Kanazawa-shi, Ishikawa

+81-76-265-2333

wakabayashi@staff.kanazawa-u.ac.jp

Complete

Sept. 10, 2009

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

parallel assignment

treatment purpose

1) Patients with histologically proven neuroblastoma
2) Positive I-131 MIBG uptake
3) Age > 1 y.o.
4) Patients with written informed consent from parents
5) Patients with ADL adequate for treatment in an isolation room. Patients with limited ADL that can be compensated by the others under the approval of the ethical board.
6) In case that high-dose treatment is chosen, bone marrow support must be secured.

1) Patients with disturbed consciousness
2) An expected life expectancy of less than 1 month
3) Limited bone marrow capacity (except patients with bone marrow support)
hemoglobin<9.0g/dl, white blood cell count<3,000, platelet count<10,000
4) Renal disorder
glomerular filtrated rate (GFR)<30ml/min/1.73m2
5) Risks for the central nerve compression syndrome that might be caused by lesion edema during the treatment
6) In case that medical practice and radiation management is difficult in an isolation room, In case of uncontrolled symptoms that require emergent medical cares, In case that urine management is difficult, In case that understanding and cooperation cannot be obtained from family members
7) When medical staffs determine that treatment cannot be properly carried out.

Both

Neuroblastoma

All patients receive standard or high-dose I-131 MIBG.

Neuroblastoma, I-131 MIBG therapy

020

1) Assessment of anti-tumor effects with tumor size and tumor markers
2) Assessment of prognosis
3) Assessment of symptoms

Incidence and type of adverse events according to Common Terminology Criteria for Adverse Events (CTCAE v 3.0)
1) Bone marrow: hemoglobin, total white blood cell, neutrophils/granulocytes, platelets
2) Gastrointestinal (radiation sickness) : appetite loss, nausea, vomiting
3) Salivary gland disorder
4) Thyroid disorder
5) Neurological disorder
6) Endocrine disorder: induction of catecholamine excess symptoms

+81-76-265-2048

None