(M1030-09-50) Rediscovery of Paclitaxel: A Novel Oral Paclitaxel Softgel Capsule Product for Improving Cancer Therapeutics

Purpose: The therapeutic efficacy of a novel oral Paclitaxel product was evaluated and compared with Albumin-bound Paclitaxel (Abraxane), Paclitaxel injection (Taxol), and two VEGF inhibitors Lenvatinib and Sorafenib in Balb/c nude mice bearing PDX gastric cancer, liver cancer, NSCLC, breast cancer, and ovarian cancer, therapeutic parameters including tumor volume, tumor growth inhibition (TGI), and treatment-to-control ratio (T/C) were compared among different treatment groups.

Methods: Abraxane and Taxol were administrated at 30 mg/Kg and 15 mg/Kg by IV infusion, while Lenvatinib and Sorafenib were administrated orally at 30 mg/Kg. The drug tolerance, cytotoxicity and safety of the oral Paclitaxel formulations were evaluated in Balb/c nude mice and beagle dogs. The tumor and tissue distribution of Paclitaxel in NCI-N87 gastric cancer-bearing mice after administration of oral Paclitaxel formulation, Abraxane and Taxol was investigated. The therapeutic efficacy of the oral Paclitaxel softgel capsules in a 15-year old Labrador Retriever with metastatic NSCLC was studied.

Results: The oral Paclitaxel formulation administrated at 100 mg/Kg demonstrated significant better therapeutic efficacy than Abraxane and Taxol for NCI-N87 gastric cancer-bearing mice while the same oral dose demonstrated noninferior therapeutic efficacy to Abraxane and but still significant better therapeutic efficacy than Taxol in Hs467T gastric cancer-bearing mice. The oral Paclitaxel formulation administrated at 180 mg/Kg demonstrated noninferior therapeutic efficacy to Lenvatinib, and significant better therapeutic efficacy than Sorafenib for Hep G2 liver cancer-bearing mice; while the same oral dose showed inferior therapeutic efficacy to Lenvatinib but noninferior therapeutic efficacy to Sorafenib for Huh-7 liver cancer-bearing mice. The oral Paclitaxel formulation administrated at 100 mg/Kg demonstrated significant better therapeutic efficacy than Abraxane and Taxol for NCI-H358 NSCLC-bearing mice. The oral Paclitaxel formulation administrated at 100 mg/Kg demonstrated noninferior therapeutic efficacy to Abraxane and significant better therapeutic efficacy than Taxol for MDA-MB-231 breast cancer-bearing mice. The oral Paclitaxel formulation administrated at 100 mg/Kg demonstrated noninferior therapeutic efficacy to Abraxane and significant better therapeutic efficacy than Taxol for SK-OV-3 ovarian cancer-bearing mice. The Paclitaxel concentration in gastric tumor was much higher for oral formulation than Abraxane and Taxol after administration for 2 hours, distribution of Paclitaxel in tumor between 6-24 hour was similar. The Maximum Tolerated Dose (MTD) of the oral Paclitaxel formulation was ≥ 200 mg/Kg in mice when dosing at Q1Dx3Weeks and ≥ 4.0 mg/Kg in beagle dogs when dosing at Q3Dx3Weeks, there were no significant body weight loss, tissue damage and animal death observed during the GLP-validated long-term safety assessment study. The oral Paclitaxel formulation demonstrated better or noninferior therapeutic efficacy in five different PDX tumor-bearing mice compared with marketed drugs, good safety and low cytotoxicity were observed in both mice and beagle dogs in long-term safety studies. The oral Paclitaxel softgel capsules administrated at low dose showed significant therapeutic efficacy in metastatic NSCLC treatment for the Labrador Retriever.

Conclusion: In conclusion, the oral Paclitaxel softgel capsule product showed promising therapeutic efficacy for various cancer treatment in preclinical studies, and great potential for conducting “Chemotherapy at Home” with significant lower medical costs. The oral Paclitaxel softgel capsule product is progressing for IND submission in both US and China.

Oral and Injectable Paclitaxel Therapeutic Efficacy Comparison 1


Oral and Injectable Paclitaxel Therapeutic Efficacy Comparison 2