Phase I expansion cohort to evaluate the combination of bevacizumab, sorafenib and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumours.

BACKGROUND: Angiogenesis is critical for tumour growth and metastasis. Dual inhibition of vascular endothelial growth factors and platelet-derived growth factor receptors suppresses angiogenesis. This expansion cohort of a phase I study targeted angiogenesis with sorafenib, bevacizumab and low-dose cyclophosphamide in children and young adults with recurrent solid tumours. METHODS: An expansion cohort including patients with refractory or recurrent solid tumours was enrolled and received bevacizumab (15 mg/kg IV, day 1), sorafenib (90 mg/m2 po twice daily, days 1-21) and low-dose cyclophosphamide (50 mg/m2 po daily, days 1-21). Each course was 21 days. Toxicities were assessed using Common Terminology Criteria for Adverse Events, v3.0, and responses were evaluated by Response Evaluation Criteria in Solid Tumors criteria. Serial bevacizumab pharmacokinetic (PK) studies were performed during course 1. RESULTS: Twenty-four patients (15 males; median age 14.5 yrs; range 1-22 yr) received a median of 6 courses (range 1-18). Twelve patients had a bone or soft tissue sarcoma. The most common grade III/IV non-haematologic toxicities were hypertension (N = 4), hand/foot rash (N = 3) and elevated lipase (N = 3). The most common grade III/IV haematologic toxicities were neutropenia (N = 7) and lymphopenia (N = 17). Three patients (2 synovial sarcoma, 1 rhabdoid tumour) achieved a partial response and 18 had stable disease. The progression-free survival at 3 and 6 months were 78.1% (95% confidence interval [CI] 60.6-95.6%) and 54% (95% CI 30.2-78.2%), respectively. Bevacizumab PKs in 15 patients was similar to published adult PK results. CONCLUSIONS: Intravenous bevacizumab combined with oral sorafenib and low-dose cyclophosphamide was tolerated and demonstrated promising activity in a subset of childhood solid tumours.

Operative and Immediate Postoperative Differences Between Traditional Multiport and Reduced Port Laparoscopic Total Splenectomy in Pediatric Patients.

BACKGROUND: Laparoscopy offers many benefits to splenectomy, such as reduced incisional pain and shortened hospital duration. The purpose of this study is to evaluate procedural and outcome differences between multiport (MP) and reduced port (RP) splenectomy when utilized to treat children. PATIENTS AND METHODS: An institutional review board approved retrospective analysis of all consecutive laparoscopic total splenectomies performed at a single institution between January 2010 and October 2015 was conducted. We evaluated demographics, surgical technique, instance of conversion, operative duration, estimated blood loss, need for intraoperative blood transfusion, postoperative length of stay, time to full feeds, complications, and follow-up duration. RESULTS: Over a 5-year period, 66 patients less than 20 years of age underwent laparoscopic total splenectomy. RP splenectomy was attempted in 14 patients. The remaining 52 were MP operations. Populations were comparable with regard to demographics. Preoperative splenic volumes (mL) were greater in the RP population (median [IQR]: 1377 [747-1508] versus 452 [242-710], P = .039). RP splenectomy demonstrated no difference compared to MP splenectomy in operative time (153 versus 138 minutes, P = .360), estimated blood loss (120 versus 154 mL, P = .634), or percent of cases requiring intraoperative blood transfusion (14 versus 23, P = .716). By the first postoperative day, 57% of RP and 17% of MP patients could be discharged (P = .005). Thirty-day readmission rates were similar, at 7% for RP and 8% for MP operations. Fever was the indication for all readmissions. Mean duration of follow-up is 28 months for MP and 13 months for RP cases. CONCLUSION: A reduced number of ports can be safely utilized for total splenectomy in pediatric patients without increasing procedural duration or need for intraoperative blood transfusion. In addition, rate of discharge on the first postoperative day was significantly higher in the RP splenectomy group.