A Phase I Trial of Nab‐Paclitaxel in Combination With Gemcitabine for Relapsed/Refractory Pediatric Solid Tumors

Background The single‐agent pediatric maximum tolerated dose (MTD) of nab‐paclitaxel is significantly higher than adult dosing. We conducted a Phase I trial to establish the MTD/recommended Phase 2 dose (RP2D) of nab‐paclitaxel with gemcitabine in children with relapsed/refractory solid tumors. Methods Nab‐paclitaxel was administered intravenously with fixed‐dose gemcitabine on days 1, 8, and 15 of 28‐day cycles. Three dose levels (DL) of nab‐paclitaxel, 180, 210, and 240 mg/m 2 , were evaluated using a rolling six design. Toxicity, nab‐paclitaxel pharmacokinetics (PK), and radiologic responses were evaluated. Pretreatment tumor tissue was assessed for SPARC and CAV‐1. Results Twenty‐four patients enrolled, 22 received therapy, and 20 were evaluable for dose‐limiting toxicity (DLT): 17 during dose escalation and 3 in dose expansion at the MTD. Median age was 12.5 years. Diagnoses included osteosarcoma ( n = 11), neuroblastoma ( n = 4), and rhabdomyosarcoma ( n = 4). At the starting dose level (gemcitabine 1000 mg/m 2 , nab‐paclitaxel 180 mg/m 2 ), two of five patients experienced DLT, prompting an amendment lowering gemcitabine to 675 mg/m 2 /dose. Post‐amendment, nab‐paclitaxel 240 mg/m 2 /dose with gemcitabine 675 mg/m 2 /dose was identified as the MTD. Grade ≥3 hematologic toxicities were common. Two patients experienced a partial response (Wilms tumor and osteosarcoma), and PK exhibited linearity across DL. SPARC immunoreactivity was present in most tumors, while CAV‐1 immunoreactivity was infrequent. Conclusions The MTD/RP2D of nab‐paclitaxel with gemcitabine in patients with relapsed/refractory pediatric solid tumors is nab‐paclitaxel 240 mg/m 2 /dose and gemcitabine 675 mg/m 2 /dose on days 1, 8, and 15 of 28‐day cycles; responses were limited in this patient population.