Vion says Cloretazine, either alone or in combination, reduces tumors, improves survival

By Elaine Rigoli

Tampa, Fla., April 4 - Vion Pharmaceuticals, Inc. released data at the annual meeting of the American Association of Cancer Research being held this week in Washington, D.C., including the results from two experiments that examined the antitumor effects of Cloretazine alone and in combination with cytarabine (Ara-C) and fludarabine (Ara-A) in murine tumor models.

In one experiment, the combination therapy of 10 mg/kg of Cloretazine plus 50 mg/kg Ara-C achieved 100% survival by day 68 post-implantation in CDF1 or BDF1 mice implanted with the murine leukemia, compared to 90% for Cloretazine monotherapy and 0% for Ara-C monotherapy.

In a separate experiment of 10 mg/kg Cloretazine and five doses of 70 mg/kg Ara-A every other day, at day 65 post-implantation, the combination therapy yielded a 90% survival rate, compared to 40% for Cloretazine alone and 0% for Ara-A alone, according to a news release.

Vion also released data from a study of VNP40541 (a hypoxia-selective compound that releases the same active agent as Cloretazine) with a single agent and in combination with conventional anticancer agents such as cyclophosphamide, gemcitabine, paclitaxel, etoposide and cisplatin in murine tumor models.

Two enantiomers (R-KS119W and S-KS119W) were evaluated and R-KS119W was chosen for further development based on a better toxicity profile, the release said.

Both enantiomers demonstrated tumor inhibition ranging from 52% to 85% in various tumor models.

VNP40541 was also evaluated in combination regimens in order to complement its activity against hypoxic tumor cells with agents that preferentially attack the well-oxygenated, actively growing cell populations within tumors.

All the different combination therapies were more efficacious than VNP40541 or any other agent alone, and tumor growth inhibition ranged from 55% to 98%, the release said.

Vion, based in New Haven, Conn., develops cancer therapeutics.

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