Use of paclitaxel carried in lipid core nanoparticles in patients with late-stage solid cancers with bone metastases: Lack of toxicity and therapeutic benefits

Abstract

^{Patients with heavily pretreated, late-stage cancer and bone metastasis are usually poor candidates for further chemotherapy. Previously, we showed that association to lipid nanoparticles (LDE) drastically decreases the toxicity of anti-cancer drugs. Here, we tested the hypothesis that paclitaxel (PTX) carried in LDE could benefit end-of-life patients with painful bone metastases that had been previously treated with conventional PTX. Methods: Eighteen consecutive patients with late-stage cancer, 8 with breast, 5 with prostate and 5 with lung carcinoma, aged 59±9 years, were included in this study. All were receiving opioid medication. LDE-PTX was administered at 175 mg/m 2 every 3 weeks until disease progression. Clinical imaging examinations and serum biochemistry determinations were performed to monitor disease progression. Intensity of bone pain, use of opioid medications and occurrence of pathological bone fractures were also evaluated. Results: In total, 104 chemotherapy cycles were performed and none of the patients showed clinical and laboratorial toxicities or pathological bone fractures. In all patients, pain was reduced so as to allow substitution of non-opioid for opioid medication. Median progression-free survival (PFS) was four months (95% CI 2.4-5.5), but in five patients PFS was longer than 6 months. Conclusions: Absence of observable clinical and laboratorial toxicities from LDE-PTX treatment, improvement of bone pain and the possible effect on PFS in some patients, despite previous use of conventional PTX, suggest that LDEPTX merits further clinical investigation .}

Keywords: Artificial nanoparticles; Bone metastases treatment; Drug targeting; LDL receptor; Pain relief.

Fig. 1

Progression-free period of 18 end-of-life patients with primary breast (patients no. 1–8), prostate (patients no. 9–13) and lung carcinoma (patients no. 14–18) and bone metastases treated with LDE-PTX.

Fig. 2

Representative photomicrographs of immunohistochemistrical staining for LDL receptors (LDLR) (A-C) or negative control (D-F) in primary tumor tissues: breast cancer (A and D), prostate cancer (B and E) and lung cancer (C and F). Brown staining indicates the expression of lipoprotein receptors immunostained by 3,30-diamino-benzidine chromogen. Negative control was performed which the primary antibody was replaced by bovine serum albumin. x200.