Edatrexate

Definition

Edatrexate is an investigational (experimental) medicine similar to methotrexate used to stop growth of cancer and formation of new cancer cells.

Purpose

Edatrexate has been shown to have anticancer activity in research studies in patients with lung cancer, head and neck cancer, breast cancer , and non-Hodgkins lymphoma.

Description

Edatrexate is an anticancer drug that belongs to a family of drugs called antimetabolites. It is an antagonist of folic acid closely related to methotrexate in its structure and antitumor activity. However, edatrexate has several potential advantages over methotrexate, including better transport across cancer cell membranes (walls surrounding cancer cells), increased selectivity for tumor cells, and greater antitumor effect. Edatrexate inhibits formation of genetic material and reproduction of cancer cells by inhibiting a certain enzyme needed to make folic acid. Without folic acid, formation of protein and new genetic material in cancer cells cannot occur. Unlike methotrexate, edatrexate has additive activity when used with cisplatin (a chemotherapy agent often used to treat non-small cell lung cancer) in animal studies. It also showed additive anticancer effects with cyclophosphamide , paclitaxel and docetaxel .

Edatrexate has been used in combination with paclitaxel, cisplatin, clyclophosphamide, mitomycin, or vinblastine in research studies. Leucovorin has been shown to be effective in reducing edatrexate side effects, but it may also decrease its antitumor effectiveness.

Recommended Dosage

Adults

SOLID TUMORS (LUNG, BREAST, HEAD AND NECK CANCER).

Doses vary between different chemotherapy protocols. The most commonly used dose in research studies was 40-80 mg per square meter of body surface area given as intravenous infusion once a week. Maximum tolerated dose when edatrexate was used in combination with paclitaxel was 120 mg per meter square per week.

Children

There is no data available on dosing and use of edatrexate in children.

Precautions

To maximize treatment effects, patients receiving edatrexate should observe certain guidelines. Including any modifications given by the oncologist, these guidelines should include regular visits with the oncologist and laboratory testing for white blood cell count, kidney, liver, and bone marrow function. Patients should: avoid any immunizations not approved or prescribed by the oncologist; avoid contact with individuals taking or who have recently taken oral polio vaccine, or individuals who have an active infection; wear a protective facemask when necessary; avoid prolonged or direct exposure to sunlight, as some patients experience an increased sensitivity; ask for specific instructions on oral hygiene procedures to reduce the risk of gum abrasion, and avoid touching the eye and nasal areas unless hands have been properly washed immediately prior to contact. To reduce bleeding and bruising complications, patients should exercise extreme caution when handling sharp instruments and decline participation in contact sports. Prior to treatment, the patient's medical history should be thoroughly reviewed to avoid complications that might arise from previous conditions such as gout, kidney stones or kidney disease, liver disease, chick-enpox, shingles, intestinal blockage, colitis, suppressed immune system, stomach ulcers, mouth sores, or a history of allergic reactions to various drugs.

The oncologist should also be made aware if the patient is pregnant or if there is the possibility the patient might be pregnant, or if the patient is a breast-feeding mother. Only prescribed medications or over the counter (OTC) drugs approved by the oncologist should be taken by a patient receiving edatrexate.

Side effects

The side effect profile of edatrexate is similar to that of methotrexate, with mouth ulcers as the dose-limiting toxicity. Other side effects include bone marrow suppression and decreased formation of all blood elements, diarrhea , skin rash, nausea, vomiting, inflammation of the lungs (pneumonitis) and mild increase in liver function tests.

Interactions

There is no published information available at this point about any potential drug or food interactions with edatrexate. As a general rule, vaccines should be avoided due to the immunosuppressive action of edatrexate, and alcohol should be avoided to reduce the risk of liver complications.

Olga Bessmertny, Pharm.D.

KEY TERMS

Bone marrow

—The tissue filling the cavities of bones.

Non-Hodgkin's lymphoma

—Lymphomas are some of the most treatable cancers with cure rates around 50% in 1990's. Non-Hodgkin's lymphoma mainly affects people over 50 years of age and has been more difficult to treat than the Hodgkin's type. There has been an increase in non-Hodgkin's lymphoma cases in the last two decades in patients with HIV.