A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors.

Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600 mg/d; cohort 2, 1000 mg/d for 2 weeks, then 800 mg/d. Primary objectives assessed pexidartinib safety and tolerability, and determined the recommended phase 2 dose; secondary objectives evaluated efficacy and pharmacokinetic profile. Results All 11 patients (6 males, 5 females; median age 64, range 23-82; cohort 1 n = 3; cohort 2 n = 8) experienced at least one treatment-emergent adverse event; 5 experienced at least one grade ≥ 3 adverse event, most commonly (18%) for each of the following: increased aspartate aminotransferase, blood alkaline phosphatase, gamma-glutamyl transferase, and anemia. Recommended phase 2 dose was 1000 mg/d for 2 weeks and 800 mg/d thereafter. Pexidartinib exposure, area under the plasma concentration-time curve from zero to 8 h (AUC0-8h), and maximum observed plasma concentration (Cmax) increased on days 1 and 15 with increasing pexidartinib doses, and time at Cmax (Tmax) was consistent throughout all doses. Pexidartinib exposure and plasma levels of adiponectin and colony-stimulating factor 1 increased following multiple daily pexidartinib administrations. One patient (13%) with tenosynovial giant cell tumor showed objective tumor response. Conclusions This was the first study to evaluate pexidartinib in Asian patients with advanced solid tumors. Pexidartinib was safe and tolerable in this population at the recommended phase 2 dose previously determined for Western patients (funded by Daiichi Sankyo; clinicaltrials.gov number, NCT02734433).

Thyroid lobe size predicts risk of postoperative temporary recurrent laryngeal nerve paralysis.

OBJECTIVES: In patients who had undergone thyroidectomy in Japan for benign tumor, we determined whether thyroid lobe size correlates with temporary recurrent laryngeal nerve paralysis (T-RLNP). METHODS: We retrospectively collected medical record data on usage of intraoperative neuromonitoring, laterality of thyroidectomy, amount of bleeding during surgery, duration of surgery, and whether the surgeon was a board certified otorhinolaryngologist as determined by the Oto-Rhino-Laryngological Society of Japan. Thyroid size was measured in preoperative axial computed tomography (CT) images. Receiver operating characteristic (ROC) curve analysis was used to determine the thyroid size that predicted a high risk of T-RLNP or permanent recurrent laryngeal nerve paralysis (P-RLNP). RESULTS: Of the 146 eligible patients identified, 9 (6.2%) developed T-RLNP and 2 (1.4%) developed P-RLNP. The amount of bleeding during thyroidectomy was significantly greater in T-RLNP patients than in P-RLNP patients. Thyroid sizes in CT images were significantly larger in T-RLNP patients compared to patients who did not develop RLNP (referred to hereafter as N-RLNP). ROC analysis revealed that 1.3% of thyroid lobes with an area of less than 1000.0 mm2, and 9.9% of thyroid lobes with an area of greater than 1000.0 mm2 were at risk for T-RLNP. CONCLUSION: We presented evidence that thyroid sizes, as measured on preoperative axial CT images, were larger in T-RLNP patients than in N-RLNP patients. Our results indicate a connection between benign thyroid tumor stretch injuries and T-RLNP. LEVEL OF EVIDENCE: IV.