Fruquintinib with gefitinib as first-line therapy in patients carrying EGFR mutations with advanced non-small cell lung cancer: a single-arm, phase II study.

BACKGROUND: Fruquintinib is an oral vascular endothelial growth factor receptor inhibitor. Previous gefitinib studies with anti-angiogenics show promising efficacy. This phase II trial assessed efficacy and safety of fruquintinib in combination with gefitinib, in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Fifty patients with stage IIIB/IV NSCLC and an epidermal growth factor receptor (EGFR) exon-19 deletion or exon-21 L858R mutation were enrolled between January 2017 and June 2019. Per protocol (version 1.0), patients received 4 mg fruquintinib once daily (qd) Days 1-21 of Cycle 1, using a 3-week-on/1-week-off schedule, plus continuous gefitinib 250 mg qd. If tolerated, patients proceeded to fruquintinib 5 mg qd (fruquintinib 5 mg group, n=26). Following protocol updates, dose escalation of fruquintinib from 4 mg qd to 5 mg qd was not allowed. The primary efficacy endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), time to response, duration of response and adverse events (AEs). RESULTS: ORR was 73.5% (95% CI, 58.9-85.1) and DCR was 98.0% (95% CI, 89.2-100.0). Median PFS was 14.7 months for both groups; PFS was highest for patients with exon-19 deletion (16.5 months; 95% CI, 12.9-21.2). Grade ≥3 treatment-emergent AEs occurred in 17 (65.3%; fruquintinib 5 mg,) and 11 patients (45.8%; 4 mg). Serious AEs were recorded for nine patients (fruquintinib 5 mg, six patients; 4 mg, three). CONCLUSIONS: Fruquintinib and gefitinib treatment showed an acceptable safety profile and promising efficacy in patients with NSCLC.

Sulfatinib, a novel kinase inhibitor, in patients with advanced solid tumors: results from a phase I study.

Sulfatinib is a small molecule kinase inhibitor that targets tumor angiogenesis and immune modulation. This phase I study (NCT02133157) investigated the safety, pharmacokinetic characteristics, and preliminary anti-tumor activity of sulfatinib in patients with advanced solid tumors. The study included a dose-escalation phase (50-350 mg/day, 28-day cycle) with a Fibonacci (3+3) design, and a tumor-specific expansion phase investigating the tumor response to treatment. Two sulfatinib formulations were assessed: formulation 1 (5, 25, and 50 mg capsules) and formulation 2 (50 and 200 mg capsules). Seventy-seven Chinese patients received oral sulfatinib; the maximum tolerated dose was not reached. Dose-limiting toxicities included abnormal hepatic function and coagulation tests, and upper gastrointestinal hemorrhage. The most common treatment-related adverse events were proteinuria, hypertension and diarrhea. Among 34 patients receiving sulfatinib formulation 2, one patient with hepatocellular carcinoma and eight with neuroendocrine tumors exhibited a partial response; 15 had stable disease. The objective response rate was 26.5% (9/34) and the disease control rate was 70.6% (24/34). Pharmacokinetic, safety, and efficacy data supported continuous oral administration of sulfatinib at 300 mg as the recommended phase II dose. Sulfatinib exhibited an acceptable safety profile and encouraging antitumor activity in patients with advanced solid tumors, particularly neuroendocrine tumors.

Clinical study of transcrestal maxillary sinus floor elevation with the disk-up sinus reamer / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical effect of the disk-up sinus reamer (DSR) applied to transcrestal maxillary sinus floor elevation with simultaneous placement of implants.</p><p><b>METHODS</b>Thirty-seven patients underwent transcrestal maxillary sinus floor elevation with fifty-one implants placed simultaneously using the DSR. The residual bone height (RBH) was 3 to 8 mm, (5.61 ± 1.61) mm on average. The safety of this technique and the pain index during the operation was evaluated. The final prostheses were restored in 3-6 months postoperatively. The follow-up period was 3 to 24 months. The stability and osseointegration of the implants were clinically evaluated, and the endo-sinus bone gain around the implants were measured.</p><p><b>RESULTS</b>The elevation height ranged from 2 to 8 mm, with an average of (4.75 ± 1.55) mm. There was no detectable sinus membrane perforation, no serious suffering or uncomfortable subjective sensation in any patients during operation with a pain index of (2.22 ± 0.98). During the follow-up period, no sinus complication was observed. Favorable osseointegration was obtained. There were no implants or prostheses which were loose or lost. The survival rate was 100%. The radiographic results demonstrated that the endo-sinus bone gain tended to reach stabilization after 6 months and the marginal bone loss was (1.20 ± 0.72) mm after 12 months.</p><p><b>CONCLUSIONS</b>Transcrestal maxillary sinus floor elevation with simultaneous implant placement by DSR is a safe, invasive and handy technique, with higher elevation height, fewer clinical complications and less pain. It shows satisfactory clinical results in short term and a long-term observation is still needed.</p>