The effect of picolinic acid (pyridine-2-carboxylic acid) on the efflux of divalent metal ions from multilamellar liposomes was examined to determine the possible specificity and mechanism for its reported beneficial effects on the intestinal absorption and systemic metabolism of zinc. Extraliposomal picolinic acid increased the efflux of Zn, Cu, Co, Mn, Ni, Cd, Pb, Fe(II) and Ca from the vesicles. However, when picolinic acid was trapped with Co, Cu and Zn within the liposomes, the loss of metals was reduced. In a partition study, picolinic acid increased the aqueous solubility of Zn, Cu, Co and Cd at alkaline pH, but did not transfer the metal to an organic bulk phase of chloroform. It is proposed that picolinic acid does not act as an ionophore and that any effect it may have on zinc metabolism is dependent upon its unselective chelating properties, which may also lead to altered dietary and systemic compartmentation of other divalent cations.

Has clinical potential, but much more research is required

No abstract

328 Background: Following CHAARTED & STAMPEDE, upfront Docetaxel chemotherapy became standard of care for metastatic hormone-naïve prostate cancer (mHNPC). We sought to evaluate our experience in the elderly group of patients (>70 yrs) compared with the non-elderly cohort. Methods: A retrospective analysis was undertaken of 38 patients commenced on upfront docetaxel chemotherapy, from Jan 16 - Jan 17. Patients were stratified as low (LR) and high risk (HR), as per the LATITUDE study. Progression was defined as per PCWG-3 criteria. The progression free survival (PFS) was calculated as time from start of treatment to date of progression and analysed by Kaplan-Meier estimates and log-rank test. Rates of febrile neutropenia (FN) were also evaluated. Results: The median age was 69 (range: 53-80) yrs, with 50% (19/38) HR patients. The median PFS was 11.5m for progressors (P; 42%) and not reached for non-progressors (NP; 58%), (p<0.0001). Granulocyte colony stimulating factor (G-CSF) was used in 13/38 (34%) patients; these did not experience FN. The overall rate of FN was 20% where G-CSF was not used. Overall 31/38 (81.6%) completed 6 cycles of chemotherapy, with 26% requiring dose reductions (Table). Overall, of the 9/16 (56.3%) patients who progressed within 6m of completing docetaxel, 3 had Cabazitaxel as the next treatment (P: 2/3 (66.7%), median PFS 6.2m) and 6 had novel androgen receptor targeted therapy (P: 5/6 (83.3%), median PFS 3.3m). Conclusions: Upfront docetaxel is reasonably well tolerated in the elderly with comparable median PFS to younger patients. Use of GCSF significantly minimizes the risk of FN in this group and should be considered as standard of care. In patients who progress within 6m of completing docetaxel, we feel optimal sequencing to be Cabazitaxel followed by subsequent therapies.[Table: see text]

ObjectivesTo assess the efficacy and tolerability of cabazitaxel in relapsed penile cancer.MethodsThis Phase II single-arm trial was designed to recruit 17 patients with relapsed penile cancer. The primary endpoint was objective (complete + partial) response rate (ORR; Response Evaluation Criteria in Solid Tumours [RECIST] v1.1). Treatment comprised six 21-day cycles of cabazitaxel with restaging after cycles 2 and 4. The planned interim analysis was based upon the premise that if none of the first nine patients achieved ORR, trial would be stopped (α = 0.05, Simon’s 2-stage design).ResultsNine patients were recruited from four UK centres between December 2014 and August 2016. The median age was 61 (range, 27–73.6) years, and seven patients had metastases. Patients received a median of two chemotherapy cycles (range, 2–5). None of the nine patients achieved ORR and the trial was stopped. Cabazitaxel was well tolerated with no dose reductions or delays. Three patients had grade 3/4 adverse events (anaemia, vomiting, or neutropenic sepsis). The median progression-free and overall survival were 1.3 and 5.6 months, respectively.ConclusionsThe trial did not reach the threshold for further continuation of single-agent cabazitaxel. However, the observed tolerability profile supports its further investigation in combination with other agents to improve patient outcomes.