Vindesine

Key Terms: Acute lymphocytic leukemia, Intravenous, Vinblastine.

Definition

Vindesine (desacetyl vinblastine amide sulfate) is a synthetic derivative of vinblastine. Vindesine is a chemotherapy drug that is given as a treatment for some types of cancer. This drug belongs to the group of anticancer drugs known as vinca alkaloids. Vindesine is also called vindesine sulfate, desacetylvinblastine amide, DAVA, DVA, or VDS, and its brand name, Eldisine.

Purpose

Vindesine is used primarily to treat acute lymphocytic leukemia. Less frequently, it is prescribed for use in breast cancer, blast crisis of chronic myelocytic leukemia, colorectal cancer, non-small cell lung cancer, and renal cell cancer (kidney cancer).

Description

Vindesine binds to particular proteins and causes cell arrest or cell death. Metabolized by the liver, vindesine is primarily excreted through the biliary system.

Vindesine is used in other countries around the world such as Britain, South Africa, and several European countries, but it is not approved by the Food and Drug Administration, and is thus not commercially available in the U.S. Eli Lilly discontinued Eldisine in Canada in 1998 to make way for newer, more effective vinca alkaloid drugs.

For acute lymphocytic leukemia (ALL), vindesine is effective in both adult and pediatric populations. As an agent used alone, vindesine has produced response rates ranging from 5% to 63% in several clinical studies. Vindesine has been used in combination therapy using the following drugs: daunorubicin, asparaginase, prednisone, cytarabine, and etoposide.

The clinical response rate in children (41%) is better than in adults (26%) for treatment of ALL. Vindesine with combination therapy has shown very high response rates in childhood ALL.

For treatment during the blast crisis of chronic myelocytic (or myelogenous) leukemia, overall response rates of 51% have been reported in adults when vindesine was used alone or in combination therapy with prednisone. Efficacy has not been demonstrated in pediatric groups.

Vindesine may be effective in treating breast cancer. When used alone, one clinical trial reported that vindesine showed an overall response rate of approximately 19% in treating advanced breast cancer.

Vindesine in combination with cisplatin is one of the most active treatments for non-small lung cancer, but vinorelbine substituted for vindesine has shown higher response rates in treating non-small lung cancer.

Vindesine is not effective for treating acute nonlymphocytic leukemia.

Recommended Dosage

There are many dosing schedules that depend on the type of cancer, response to treatment, and other drugs that may be co-prescribed. Dosing guidelines also consider the white blood cell count.

Method of administration: Vindesine is injected intravenously through a fine needle (cannula). Alternatively, it may be given through a central line that is inserted under the skin into a vein near the collarbone.

• Intravenous administration for adults: Each one to two weeks a dose of 2-4 mg/m² is given; or each three to four weeks 1.5 mg/m²/day for five to seven days as a continuous infusion is administered.
• Intravenous administration for children: Once a week with 4 mg/m² or twice weekly with 2 mg/m².

Precautions

Vindesine may cause fertility problems in men and women. In addition, it may harm the fetus or may damage sperm; therefore, it is not recommended for women to use vindesine during pregnancy or for men to father a child while taking this drug. The physician should be alerted immediately if pregnancy occurs. Due to possible secretion into breast milk, breast-feeding is not recommended.

Other considerations:

• Vindesine is potentially mutagenic or carcinogenic (cancer-causing).
• Vindesine may cause death if injected intrathecally (into the spinal cord). It is for intravenous use only.
• Prior injection sites should be carefully inspected because tissue damage may occur days or weeks after administration.
• Hepatic dysfunction increases the neurotoxic potential of this drug.
• Alert doctors or dentists about vindesine therapy before receiving any treatment.

Side Effects

Possible side effects of vindesine therapy:

• pain or tenderness at injection site
• Hair loss (alopecia) is common.
• Vindesine can damage the surrounding tissue if it leaks into the tissue around the vein. If vindesine leaks under the skin, a burning or stinging sensation may be felt. Alert the doctor immediately if burning or stinging occurs while the drug is administered or if fluid is leaking from the site where the needle was inserted. Also tell the doctor if the area around the injection site becomes red or swollen at any time.
• Constipation or abdominal cramps. These can be alleviated by drinking plenty of water, eating a high-fiber diet, and light exercise.
• temporary decrease in white blood cell count and platelets
• Numbing of the fingers or toes may occur over the course of treatment. It may take several months to return to normal.
• Diarrhea occurs infrequently.
• mouth sores and ulcers
• Nausea and vomiting rarely occurs.
• Anaphylaxis is rare.
• Jaw pain may be severe, but it is rare.
• Thrombocytopenia (a decrease in the number of platelets in the blood) or thrombocytosis. These conditions are also rare.

Interactions

Vindesine may interact with mitomycin-C (brand name Mutamycin), causing acute bronchospasm within minutes or hours following administration. Phenytoin (brand name Dilantin) may also interact with vindesine, leading to decreased serum levels of phenytoin.

Other drug interactions may occur with:

• Itraconazole
• Live virus and bacterial vaccines. When taking immune suppressing chemotherapy drugs, live vaccinations should not be given.
• Quinupristin/dalfopristin
• Rotavirus vaccine
• Warfarin