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FDA Grants Fast-Track Designation to Thymitaq for Liver Cancer
by Rosemarie Foster, BA, MA
| Thymitaq Click on the active ingredient name to access more information. | |
| Brand Name: | Thymitaq |
| Active Ingredient: | nolatrexed dihydrochloride |
| Indication: | For the treatment of patients with unresectable hepatocellular carcinoma (not approved by FDA as of June 2000) |
| Company Name: | Zarix, Inc |
| Availability: | Not yet approved (as of June 2000); FDA designated Thymitaq as a Fast Track Product on May 1, 2000 |
Introduction
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer in the world and offers less than a 5% chance of survival. The median survival after diagnosis is less than 4 months. Unresectable HCC -- the diagnosis made in about 82% of HCC patients -- is considered incurable, with no accepted standard therapy.Thymitaq (nolatrexed dihydrochloride), manufactured by Zarix, Inc., is a new agent that may extend the survival of patients with HCC. On May 1, 2000, Thymitaq was designated by the FDA as a Fast Track Product for the treatment of unresectable HCC. Fast Track status is reserved for those drugs in development that have the potential to address unmet medical needs for life-threatening conditions. The designation may enable Zarix to obtain Priority Review of Thymitaq for unresectable HCC, reducing the time to subsequent drug approval.
How It Works
Thymitaq belongs to the group of antineoplastic drugs known as antifolates. It works by inhibiting the enzyme thymidylate synthase, which plays a key role in cancer cell proliferation. Thymitaq is the only specific, membrane-permeable non-polyglutamated thymidylate synthase inhibitor. It was designed to reduce toxicity and potential transport-associated resistance.Clinical Study Results
To date Thymitaq has been evaluated in clinical trials of 149 patients. In two phase II trials conducted in the US, patients with unresectable HCC who were treated with Thymitaq demonstrated a median survival of more than 23 weeks.In one of these studies, 41 patients with unresectable or metastatic HCC were treated with Thymitaq, which was administered as a 24-hour outpatient intravenous infusion for 5 days at a dose of 795 mg/m(2)/day as free base during each 21-day cycle. Twenty-eight patients received at least 2 courses of treatment, and 26 patients were evaluable. Two patients (8%) achieved a partial response, and 2 other patients achieved a minor response that was significant enough to allow surgical resection with curative intent. Fourteen patients (54%) achieved stable disease. The overall median survival was 7 months (10 months among patients who completed 2 cycles), and 1 patient remained free of disease at last follow-up, 37 months after surgery.
Zarix plans to initiate phase III clinical trials in the fourth quarter of 2000.
Adverse Events
Thymitaq has no end-organ toxicity. Adverse side effects reported by patients taking Thymitaq are typical of other antimetabolites -- leukopenia, thrombocytopenia, mucositis, skin rash, nausea, stomatitis, and malaise -- but are of shorter duration.
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