New anticancer agent starves tumours by disrupting their blood flow
The Institute for Drug Development, a division of The Cancer Therapy and Research Centre at The University of Texas Health Science Centre at San Antonio, announced the results of a new phase I clinical study on NPI-2358, a targeted anti-cancer agent designed to rapidly disrupt blood flow to the tumour mass, causing tumour death.
The novel agent destabilises the cells in the blood vessels leading to the tumour, resulting in a toxic effect on the cancer cells, leaving the healthy cells unharmed. The data were presented 14 April during the Annual Meeting of the American Association for Cancer Research (AACR) in San Diego, Calif.
Results presented show the novel anti-cancer agent NPI-2358 to be well tolerated by patients with solid tumours and lymphoma. Minimal side effects included intermittent nausea, fever, tumour pain and temporary hypertension, demonstrating a successful drug effect on stabilising the tumour growth.
The study, 'Phase I Dose Escalation Trial with DCE-MRI Imaging of the Novel Vascular Disrupting Agent NPI-2358,' was authored by Dr Monica Mita and her colleagues at the Institute for Drug Development, Virtual Scopics Inc., Northwestern Medical Specialties, Karmanos Cancer Institute and Nereus Pharmaceuticals.
'This vascular disrupting agent produces a rapid and selective shutdown of the established tumour vasculature. Other compounds with the same mechanism of action are also currently in clinical development and demonstrated clinical benefit as single agents and also in combination with chemotherapy agents,' said lead author Monica Mita, M.D., principal investigator at The Institute for Drug Development.
'NPI-2358 is well tolerated and demonstrated promising results in patients with advanced solid tumours. Clinical studies with NPI-2358 as a single agent and in combination are ongoing,' Dr Mita said.
NPI-2358 underwent preclinical testing at The Institute for Drug Development. This research demonstrated that the agent strengthens the effects of many other chemotherapy agents. The preclinical data suggested that the blood flow to the tumour continued to be reduced 24 hours after dosage.
In the Phase I clinical study, 25 patients with a solid tumour malignancy or lymphoma received NPI-2358 at 6-30 mg/m2 administered weekly for 15 or 30 minutes by intravenous infusion on days 1, 8 and 15 on a 28-day cycle.
A trend toward tumour blood flow decrease was demonstrated in patients evaluated above 13.5 mg/m2. Tumour pain was reported in multiple patients.
Together these findings, in addition to temporary hypertension, fever and nausea, which occurred in multiple patients, suggest NPI-2358 is affecting tumour blood flow and has biological activity at and above 13.5 mg/m2.
The recommended phase II dose was established at 30 mg/m2. No responses have been reported, although seven patients have had stable disease with pancreatic cancer, melanoma, adrenocortical carcinoma, anal squamous cell carcinoma, liposarcoma, hemangiopericytoma and colorectal carcinoma.
Preclinical data, indications of drug effect and toxicity profile support the initiation of a phase II program.
Source: University of Texas Health Science Centre at San Antonio