Product
Totect
Approval Date
September 6, 2007
Release Date
October 16, 2007
Company
TopoTarget
Class
Topoisomerase II inhibitor/chelating agent
Indication
To treat extravasation resulting from IV anthracyclinechemotherapy.
Active Ingredient
Dexrazoxane 500mg; per vial; pwd for IV infusion afterreconstitution and dilution; preservative-free.
Agencies
Padilla Speer Beardsley New York (media outreach, constituency education)
Marketing Strategy/Execution
TopoTarget USA’s sales force of 10 specialty reps has been promoting Totect to oncologynurses and physicians since the product’s launch last year. Totectis the only FDA-approved treatment for extravasation from intravenousanthracycline chemotherapy, and TopoTarget would like to see an estimated 3,600oncology departments and centers throughout the US have a kit or two on hand.Extravasation is the accidental leakage of chemotherapy drugs into surroundingtissue. TopoTarget’s message around Totect is one of “preparedness and education” to hospitalists and oncology specialists, a spokesperson told MM&M. In the event of anthracycline extravasation, early detection and rapidtreatment, within six hours of the occurrence, can prevent healthy tissuedamage. Media relations, trade advertising and industry conference participation are among the marketing channels being used. The product is sold in Europeunder the name Savene.
Also in the Pipeline(courtesy of Adis R&D Insight)
No competitor compounds in phase III or pre-registration, US
Recent MM&MCoverage
Product News
Pharmacology
The mechanism by which dexrazoxane diminishes tissue damageresulting from the extravasation of anthracycline drugs is unknown. Someevidence suggests that dexrazoxane inhibits topoisomerase II reversibly.
Dexrazoxane is also converted intracellularly to a chelating agentthat interferes with iron-mediated free radical generation thought to beresponsible, in part, for anthracycline-mediated oxidative injury.
Clinical Trials
The efficacy of Totect in reducing tissue injury followinganthracycline extravasation was studied in two, open-label, single arm,multicenter studies. In these two studies, patients were receiving single-agentanthracycline intravenously and developed extravasation symptoms near the infusionsite. In total, 80 patients were enrolled and 57 were evaluable.
The anthracyclines most commonly associated with extravasation wereepirubicin and doxorubicin. Peripheral IV sites of extravasation included thefore-arm, hand, and the antecubital area; four patients received theanthracycline via a central venous access device (CVAD).
Treatment with Totect was started as soon as possible and nolater than 6 hours after extravasation with retreatment 24-48 hours later (atotal of 3 doses). Totect was administered as 1-2 hour IV infusions through adifferent venous access location. The first and second doses were 1000mg/m2 andthe third dose was 500mg/m2.
In study 1, none of the 19 evaluable patients required surgicalintervention and none had serious late sequelae.
In study 2, one of the 38 evaluable patients required surgery. Oneadditional non-evaluable patient required surgery for tissue necrosis. Thirteenpatients had late sequelae at the event site such as site pain, fibrosis,atrophy, and local sensory disturbances; all were judged as mild except in theone patient who required surgery. None of the 4 patients with CVADs requiredsurgical intervention.
Adverse Reactions
Inj site reactions, GI upset, stomatitis, leukopenia,neutropenia, thrombocytopenia, elevated liver enzymes, pyrexia, infections.
Adults
Give once daily for 3 consecutive days by IV infusion over 1–2 hours. Initiatefirst dose as soon as possible and within first 6 hours after extravasation.Days 1 and 2: 1000mg/m2; max 2000mg. Day 3: 500mg/m2; max 1000mg. Renalimpairment (CrCl <40mL/min): reduce dose by 50%.
Children
Not recommended.
Precautions
Renal or hepatic impairment (monitor liver enzymes). Monitorfor myelosuppression; obtain blood counts periodically. Elderly. Labor & delivery.Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.
Interactions
Avoid dimethylsulfoxide (DMSO). Caution with concurrentcytotoxic agents (additive cytotoxicity).
