Iodine 131 antiferritin, a new treatment modality in hepatoma: a Radiation Therapy Oncology Group study.

Abstract

One hundred five patients with hepatoma were treated with iodine 131 antiferritin in three sequential protocols in phase 1-2 trials. Therapy began in all trials with external beam irradiation and chemotherapy. The dosimetric results with 131I antiferritin indicated that 30 mCi (8 to 10 mCi/mg immunoglobulin G [IgG]) was sufficient to saturate the tumor. Tumor-effective half-life of the radioactive antibody was 3 to 5 days and was dependent on the species of animal from which the antibody was derived. This led to a 30 mCi on day 0 and 20 mCi on day 5 treatment schedule. Toxicity was predominantly thrombocytopenia. Due to clinical remission, cyclic therapy was next developed with antibodies from different species of animals. Rabbit, pig, monkey, and bovine antibodies were determined to produce the longest tumor-effective half-life and therefore the highest dose of radiation. Integration of 15 mg doxorubicin and 500 mg 5-fluorouracil (5-FU) with 131I antiferritin was accomplished next. Remission to external beam radiation was evaluated by computed tomography (CT) scan tumor volume computations that indicated that 22% of the patients had a partial remission (PR) from initial presentation to 1 month following external irradiation and chemotherapy. From the time of radioactive antibody administration, 48% of the patients (7% complete response [CR] and 41% PR) achieved remission to 131I antiferritin. Of 79 patients evaluated by CT scan tumor volumetrics 50% of the patients (7% CR and 43% PR) remitted to the entire treatment regimen. Patients not previously treated and without metastasis who were alpha fetoprotein positive (AFP+) had a 5-month median survival compared with AFP- median survival of 10 1/2 months. There were four CRs with one being 3 years and 6 months. The longest PR was 5 years and 8 months. These studies have demonstrated the toxicity and therapeutic activity of 131I antiferritin and the emerging role of radiolabelled antibody in cancer therapy.

A single-dose toxicity study on non-radioactive iodinated hypericin for a targeted anticancer therapy in mice

“…Although Hyp is very promising and highly researched, phenomena associated with the use of Hyp and its derivatives, such as insolubilization, aggregation, fusion, and relative instability, could hinder the applications of Hyp. The relevance of the chemical and physical properties to the pharmaceutical application of Hyp has been discussed extensively [7,[18][19][20][21][22][23][24][25][26][27][28] . However, specific clinical applications become more restricted when the focus is narrowed to those newly discovered activities.…”

“…With regard to 131 I-Hyp, which was used in recent research [15] , the radio-toxicities of Iodine-131 have already been well defined in various clinical applications for many decades [25][26][27][28] . However, the chemotoxicity of 131 I-Hyp still remains unknown.…”

Improving external beam radiotherapy by combination with internal irradiation

“…90 Y, 131 I and 125 I, 111 In (for dosimetry), applied for the systemic part of CIERT are still in use today. 77,80,81 With regard to the literature, reports about integrated CIERT of solid tumours in males are rare, but several clinical trials addressing different tumour-targeting mechanisms have been conducted for three decades. 80 The most treated entities with predominantly promising reports are (recurrent) malignant glioma, meningioma, primary and secondary tumours of the liver, brain metastases (especially from NSCLC), osteoplastic bone metastases from prostate cancer, primary breast cancer, malignant pheochromocytoma and paraganglioma.…”

Radioimmunotherapy of malignancy using antibody targeted radionuclides

“…In order to give repeated injections of labelled targeting antibody and avoid patient sensitization to foreign antibody these authors used polyclonal antibody from a different species for each injection (Order et al, 1985). There has not been sufficient time for a realistic clinical assessment of the value of McAbs in radioimmunotherapy (RIT); however, it would seem that the more specific targeting potentially obtainable with…”

“…Second, the improved gamma and positron tumour immunoimaging that can be obtained with McAbs has illustrated clearly that radionuclides can be concentrated in tumours. Third, there have been a number of reports indicating clinical response to antibody-targeted radionuclides (Order et al, 1980a(Order et al, 1985Carrasquillo et al, 1984). Order and his colleagues at the Johns Hopkins Hospital, Baltimore, have been using radiolabelled polyclonal antibodies as a part of their treatment of carcinoma of the liver (hepatocellular and cholangiocarcinoma) for some years, and have reported clinical responses with radiation/drug regimens which include 131I-labelled anti-ferritin and anticarcinoembryonic antigen (CEA).…”