Safety and Toxicity of Iopofosine I-131 with External Beam Radiation Therapy (EBRT) in Recurrent or Metastatic Head and Neck Cancer (HNC): Results of a Phase 1 Study

Purpose/Objective(s)

Retreatment of recurrent HNC is often limited by tumor adherence to critical structures or normal tissue tolerance to radiation therapy. Iopofosine I-131 (CLR 131) is a novel targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to malignant tumor cells optimized through specialized regions called lipid rafts. Radiation exposure is selective to cancer cells due to the interaction of the PLE with the highly enriched lipid rafts of the plasma membrane, which are non-reliant on cell surface markers. In this trial, CLR 131 given with a reduced dose of EBRT will be safe and produce favorable tumor response rates.

Materials/Methods

All patients (pts) must have previously received treatment with curative intent radiotherapy to the HN region. Pts may have metastatic disease, as long as the site of recurrence is eligible for radiotherapy and takes precedence over systemic treatment. Eligible pts must demonstrate uptake of CLR 131 as indicated via SPECT/CT imaging after administration of a CLR 131 test dose. Pts received 2 doses of CLR 131 (days 1 and 8) with SPECT/CT imaging performed to quantitate the biodistribution of CLR 131. The Monte Carlo method was utilized to calculate the absorbed dose of CLR 131 by the targeted tumor. Pts subsequently received EBRT to complete the designated radiation dose outlined in the standard of care reirradiation plan (60-70 Gy).

Results

Sixteen pts were consented, and 12 were treated on study. Four pts were ineligible (2 had insufficient CLR 131 uptake, 2 had rapidly progressive disease). Six pts were treated at first recurrence, 6 pts had multiply recurrent disease, and 2 pts had metastatic disease. All pts completed treatment with CLR 131 and EBRT. One pt died from aspiration pneumonia unrelated to CLR 131 but possibly related to EBRT. The median total absorbed tumor dose of CLR 131 was 6.23 Gy [range 2.65 - 8.69 Gy]. Eight pts experienced gr 4 non-DLT hematologic toxicities (2 anemia, 8 leukopenia, 5 thrombocytopenia) at least probably attributed to CLR 131, which was consistent with the expected toxicity profile. The hematologic toxicities occurred during weeks 6-8 from the first dose of CLR 131, and resolved within 3 weeks without sequelae. There were no treatment related gr 3-4 non-hematologic toxicities.

Conclusion

CLR 131 at a fractionated dose of 15.6 mCi/m2 in combination with EBRT was safe and tolerable in pts with recurrent/metastatic HNC. Observed myelosuppression was consistent with the known toxicity profile of CLR 131. The Monte Carlo method provides a novel approach for calculating the tumor-absorbed dose of radionuclide agents, allowing for accurate tumor targeting and personalized dosing strategies in future combination therapy studies, which may improve efficacy and reduce toxicity.