Oral paclitaxel in the treatment of metastatic breast cancer (MBC) patients.

Abstract

1084 Background: Intravenous (IV) paclitaxel is an effective treatment for breast cancer. Oral administration paclitaxel is preferable to IV regarding minimizing IV injections, anaphylactic reactions to cremaphor, steroid pre-medications, hospital visits, and relevant costs. However, paclitaxel has poor oral absorption due to active excretion by P-glycoprotein (P-gp) in the intestinal cells. Oraxol (Athenex, USA) is an oral paclitaxel and HM30181, a novel oral inhibitor of intestinal P-gp which enables the oral administration of paclitaxel. We report the final results of a pharmacokinetics (PK) study, including clinical response and tolerability of Oraxol in treatment of metastatic breast cancer patients. Methods: Multicenter, single-arm, open-label, PK study of Oraxol (HM30181A at 15mg, plus oral paclitaxel 205mg/m2) administered orally for 3 consecutive days weekly for up to 16 weeks. Paclitaxel PK was assessed at week-1 and week-4. Tumor Response was measured at weeks 8 and 16 using RECIST criteria 1.1. Toxicity was assessed using CTCAE v4.03. Results: Twenty-eight MBC patient were studied with a mean age of 56.6 years (range: 38 - 79 yrs). 26 patients had failed mutiple previous chemotherapies. There were 11 (42.3%) partial response, 12 (46.2%) stable disease and 3 (11.5%) progressive disease in 26 evaluable patients. Three patients had treatment-related SAEs (grade ≥3 neutropenia) and all patients recovered completely. PK results showed that the AUC of oral paclitaxel at week-1 was reproducible at week-4 (3050 to 3594 ng-hr/mL). Conclusions: Oral paclitaxel showed very encouraging anti-cancer activity in MBC patients who failed previous chemotherapies with acceptable toxicity. Weekly oral paclitaxel can achieve paclitaxel exposure similar to that of weekly IV paclitaxel (80mg/m2) reported previously. PK of oral paclitaxel is reproducible. Clinical trial information: NCT03165955.

Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer

“…13 A 16-week phase II study of oPac 1 E once daily for 3 consecutive days per week in 28 women with previously treated metastatic breast cancer (mBC) reported a 42% best response rate. 14 This phase III trial evaluated the efficacy and safety of oPac 1 E once daily for 3 consecutive days per week compared with IVpac at the approved dose and schedule, 175 mg/m 2 once every 3 weeks in patients with mBC.…”

Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance

“…To inhibit the pumping capability of P-gp, a third-generation inhibitor (HM30181A, HM in short) was used in this study that can selectively and potently inhibit the P-gp function 30 . However, HM is insoluble in water and was used only through oral delivery in previous studies to inhibit P-gp in the intestinal endothelium.…”

History of Paclitaxel and Oral Paclitaxel – Clinical Data and Future

“…Athenex, USA, has developed "Oraxol," which is an oral paclitaxel and HM30181 (encequidar), a novel oral inhibitor of intestinal P-gp which enables the oral administration of paclitaxel. [9] Encequidar possesses inhibitory activity specific against P-gp and has minimal oral absorption. This distinguishing characteristic of encequidar limits its inhibitory action locally to the luminal endothelium of gastrointestinal tract and thus improves the absorption of paclitaxel.…”

“…The single-arm, open-label, multicenter, pharmacokinetic trial was conducted wherein oraxol (HM30181A at 15 mg plus oral paclitaxel 205 mg/m 2 ) was administered orally for 3 consecutive days, every week for up to 16 weeks. [9] In this trial, pharmacokinetic parameters for oral paclitaxel were characterized at week-1 and week-4, tumor response was evaluated at weeks 8 and 16 using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and toxicity profile was assessed using Common Terminology Criteria for Solid Tumors version 4.03.…”