We describe the development and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors. DTXL-TNP is targeted to prostate-specific membrane antigen, a clinically validated tumor antigen expressed on prostate cancer cells and on the neovasculature of most nonprostate solid tumors. DTXL-TNP was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug release properties. Pharmacokinetic and tissue distribution studies in rats showed that the NPs had a blood circulation half-life of about 20 hours and minimal liver accumulation. In tumor-bearing mice, DTXL-TNP exhibited markedly enhanced tumor accumulation at 12 hours and prolonged tumor growth suppression compared to a solvent-based DTXL formulation (sb-DTXL). In tumor-bearing mice, rats, and nonhuman primates, DTXL-TNP displayed pharmacokinetic characteristics consistent with prolonged circulation of NPs in the vascular compartment and controlled release of DTXL, with total DTXL plasma concentrations remaining at least 100-fold higher than sb-DTXL for more than 24 hours. Finally, initial clinical data in patients with advanced solid tumors indicated that DTXL-TNP displays a pharmacological profile differentiated from sb-DTXL, including pharmacokinetics characteristics consistent with preclinical data and cases of tumor shrinkage at doses below the sb-DTXL dose typically used in the clinic.

Serlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274).

Thirty patients with hairy cell leukemia were treated with recombinant interferon alpha-A (rIFN alpha A; Roferon-A); seven were previously untreated. Nine complete and 17 partial remissions were documented by bone marrow core biopsies. All patients' peripheral blood hematologic indexes either improved or normalized. Twelve of 13 patients with retroperitoneal or mediastinal adenopathy obtained remissions of tumor masses. All seven patients with splenomegaly showed prompt reduction in the size of the spleen to normal size. The incidence of complete remissions was significantly higher (P = .02) in previously untreated patients (5 of 7) than in those in whom splenectomy had been performed (4 of 23), a result presumed to be related to the pretreatment tumor burden. rIFN alpha A was well tolerated; mild fatigue was the most frequent complaint. In most patients, tumor remissions resulted in an improved quality of life: they eliminated the need for transfusing blood products and reduced the incidence of infections, and immune deficits were apparently restored in some of the patients. We conclude that rIFN alpha A is an effective therapy for all stages of hairy cell leukemia including previously untreated or newly diagnosed patients.

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