Successful treatment switch from lenvatinib to sorafenib in a patient with radioactive iodine-refractory differentiated thyroid cancer intolerant to lenvatinib due to severe proteinuria.

Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib. She continued to receive lenvatinib but with repeated dose interruptions and reductions due to continuous proteinuria. Because of severe and persistent proteinuria as well as newly developed renal impairment, lenvatinib was suspended after two years of treatment. After the 7-month suspension, her proteinuria and renal impairment were partially improved, but her lung metastases progressed. Because she was unable to tolerate previous treatment with lenvatinib, sorafenib was started. At 7 months of treatment with sorafenib, her lung metastases shrank and she could continue sorafenib without exacerbation of proteinuria or renal impairment. This case may suggest that sorafenib does not exacerbate the proteinuria or renal impairment induced by lenvatinib, and may be an effective treatment option for RAI-refractory DTC patients who are unable to tolerate lenvatinib.

Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss.

The sigma-1 receptor, which is expressed throughout the brain, provides physiological benefits that include higher brain function. The sigma-1 receptor functions as a chaperone in the endoplasmic reticulum and may control cell death and regeneration within the central nervous system. Cutamesine (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) is a ligand selective for this receptor and may mediate neuroprotective effects in the context of neurodegenerative disease. We therefore assessed whether cutamesine protects the inner ear from noise-induced or aging-associated hearing loss. Immunohistochemistry and Western blotting revealed that the sigma-1 receptor is present in adult cochlea. We treated mice with 0, 3, or 30 mg/kg cutamesine from 10 days before noise exposure until the end of the study. All subjects were exposed to a 120-dB, 4-kHz octave-band noise for 2 hr. We assessed auditory thresholds by measuring the auditory-evoked brainstem responses at 4, 8, and 16 kHz, prior to and 1 week, 1 month, or 3 months following noise exposure. For the aging study, measurements were made before treatment was initiated and after 3 or 9 months of cutamesine treatment. Damage to fibrocytes within the cochlear spiral limbus was assessed by quantitative histology. Cutamesine significantly reduced threshold shifts and cell death within the spiral limbus in response to intense noise. These effects were not dose or time dependent. Conversely, cutamesine did not prevent aging-associated hearing loss. These results suggest that cutamesine reduces noise-induced hearing loss and cochlear damage during the acute phase that follows exposure to an intense noise.

Outpatient administration of radioactive iodine after total thyroidectomy for pediatric thyroid cancer: a report of three cases.

Radioactive iodine is used as an anti-cancer reagent for papillary and follicular thyroid carcinomas. Patients that are administered a large dose of radioactive iodine are required to stay alone in an isolated room for several days. Some young children with thyroid carcinoma who cannot take care of themselves are not able to undergo this therapy. We tried outpatient administration of (131)I for these patients. In Japan, administration for outpatients is restricted to 500 MBq (13.5 mCi). We administrated 13 mCi (131)I to three patients suffering from pediatric thyroid carcinomas. One patient with recurrent follicular carcinoma in the neck showed complete loss of the thyroid bed and an undetectable level of serum thyroglobulin 7 months after the first administration of (131)I, and no further recurrence was observed after 5 years. Another patient with multiple lung metastases showed weakened uptake of (131)I in the lung and an evident decrease in serum thyroglobulin after administration. However, the last patient with lung metastases with a low (131)I uptake showed no evident change in either (131)I uptake in the lung nor the serum thyroglobulin level. Administration of 13 mCi (131)I was effective in two of three patients. Thus, it is worth considering this therapy as a practical option for pediatric thyroid carcinoma in the countries in which outpatient administration of a large dose of (131)I is restricted.