Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine

Abstract

Oral irinotecan can be safely administered as a single agent or in sequential combination with capecitabine. The efficacy of oral irinotecan should be explored further as a potentially convenient alternative to IV chemotherapy.

The Tumor Suppressor Gene TUSC2 (FUS1) Sensitizes NSCLC to the AKT Inhibitor MK2206 in LKB1-dependent Manner

“…Previously, we have demonstrated the efficacy of intravenous systematic nanovesicle TUSC2 gene delivery in NSCLC mouse models [4]-[7]. To validate the antitumor activity of TUSC2-MK2206 in vivo , we evaluated the effect of this combination on inhibiting tumor growth in an LKB1-defective human H322 lung cancer xenograft mouse model.…”

“…Recently, we have demonstrated that exogenous expression of TUSC2 in non-small cell lung carcinoma cells, deficient of its expression, significantly inhibited tumor cell growth [5], [6]. In addition, intravenous systemic delivery of TUSC2 to distant tumors, via intravenous N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP): cholesterol nanovesicles, suppressed tumor growth and progression in orthotopic human lung cancer xenograft models, and in a phase I clinical trial of stage 4 lung cancer patients who had progressed on chemotherapy [4]–[7].…”

Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38

“…They allow self-medication, flexibility in the dosing schedule and more importantly minimize the need for hospitalisation, hence dramatically reducing the cost of treatment [97]. The current limitations for oral delivery of SN38 are poor and erratic absorption (10-20% as oral CPT-11) and thus a variable therapeutic response [39,41,98]. Furthermore, the debilitating diarrhoea which is due to the free SN38 generated in the intestine during enterohepatic recirculation, and the limited drug absorption to the systemic circulation due to the intestinal metabolism by CYP enzymes during absorption and the P-gp efflux [26,27,44,99] also limit the oral delivery of SN38 or CPT-11 directly.…”

Effects of herbal supplements on the bioactivation of chemotherapeutic agents

“…Irinotecan, a topoisomerase I inhibitor was also selected as a probe compound because its metabolite SN‐38 is activated by a carboxyesterase pathway rather than CYP450, thereby providing data for supplement interaction with non‐CYP450 mediated activation pathways. The maximum tolerated oral dose for irinotecan as a single agent in patients with active solid tumour malignancies is 60 mg/m 2 per day …”

“…The maximum tolerated oral dose for irinotecan as a single agent in patients with active solid tumour malignancies is 60 mg/m 2 per day. [35] One difficulty in analysing the data from these experiments is that each supplement contains multiple inhibitors, functioning via different inhibition mechanisms, and these inhibitors are present over a broad range of concentrations in the supplement. Additionally, the composition of the components in the supplements may also vary as a function of product preparation or seasonal and geographical origin.…”