Suramin

views updated May 18 2018

Suramin

Definition

Suramin (suramin hexasodium; CI-1003) is a polysulfonated naphthylurea. It is a growth factor antagonist for palliative treatment in hormone-refractory prostate cancer and hormone-responsive metastatic prostate cancer.

Purpose

Suramin has been used for years to combat African sleeping sickness and river blindness but it has also been found beneficial in slowing the progression of prostate cancer. This drug is classified as an antiprotozoal or anthelminitic. In addition to combating prostate cancer, suramin has demonstrated anti-tumor activity against many types of tumors including endometrial, breast, ovarian, and lung cancer. It has a number of important biological functions for cancer treatment; it inhibits a number of growth factors and receptors needed for tumor growth including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor, and vascular endothelial growth factor. Suramin decreases blood plasma levels of insulin-like growth factors 1 and 2. Suramin also inhibits tumor antigen, DNA synthesis, cell motility, and urokinase activity. It has also demonstrated significant improvements in pain response. In one of the most recent clinical studies, published in 2001, suramin delayed disease progression, by inhibition of prostate-specific antigen levels, thus prolonging survival in prostate cancer patients. This study also demonstrated suramin delayed two other clinical study endpoints: progression-free survival (i.e. delaying disease progression) and time to pain progression.

Description

While conducting research into suramin as a potential anti-HIV agent, it was found that tumors regressed in HIV-associated cancers. This discovery led investigators to evaluate the antineoplastic effects of suramin. Unfortunately, suramin did not prove effective as an anti-HIV agent.

Suramin, under the brand name Metaret, was submitted for Food and Drug Administration (FDA) approval for treatment of hormone-refractory prostate cancer in 1997 by Warner-Lambert. However, a review by the Oncologic Drugs Advisory Committee in 1998 did not support FDA approval. It was given approval for the "List of Orphan Designations and Approvals." It has been reported to be under development by the Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) and the National Institute of Health (NIH). This drug was withdrawn in 2000 and will not be pursued for FDA approval by Pfizer, who merged with Warner-Lambert.

Recommended dosage

Since this drug is not FDA approved for cancer treatment, dosing information is not readily obtainable. Original research on suramin with continuous infusions was associated with severe toxicities. Due to these toxicities, a long half-life, and a narrow therapeutic range, there was a desire to avoid prolonged continuous infusions. During clinical trials , outpatient doses of suramin were aimed at maintaining plasma concentrations at 150 to 250 mcg/mL for three months' duration to minimize treatment exposure.

Precautions

The majority of the precautions listed below are based on suramin's use as an antiprotozoal agent.

The following precautions should be considered:

Allergies. Alert the doctor if any unusual or allergic reaction to suramin occurs or to any other substances, such as foods, preservatives, or dyes.
Pregnancy. Suramin has not been studied in pregnant women, but animal studies in animals have shown that suramin may cause birth defects or death of the fetus. Before receiving this medicine, alert the doctor if you are pregnant or if you may become pregnant.
Breast-feeding. It is not known whether suramin passes into breast milk. This issue should be discussed with a doctor for a mother who wishes to breast-feed.
Children. Suramin can cause serious side effects in any patient, so prior to adminstration to children, discuss the risks with a doctor.
Older adults. Elderly people are especially sensitive to the effects of suramin. This may increase the chance of side effects during treatment.
Other medical problems. The presence of other medical problems may affect the use of suramin. Make sure to tell the doctor about any other medical problems, especially kidney or liver disease. Patients with kidney or liver disease may have an increased chance of side effects

Due to a risk of adrenal insufficiency (which results from the inadequate production of adrenal hormones) and coagulopathy (a defect that interferes with the blood clotting mechanism), patients receiving suramin should be administered hydrocortisone and vitamin K.

Significant toxicities are associated the use of suramin. However, with careful monitoring of serum concentrations, these toxicities are manageable.

Side effects

Rash, edema, and asthenia are commonly reported, but generally mild to moderate. Malaise and fatigue are the most common dose-limiting toxicities, affecting 41% of patients in clinical trials for prostate cancer. The majority of the side effects listed below are based on suramin's use as an antiprotozoal agent. Different doses used for cancer treatment may effect the side effect profile. Abdominal pain, fever , metallic taste, and a general feeling of discomfort may be bothersome but do not usually require medical attention. These effects may disappear during treatment as the body adjusts to the medicine. Other common side effects are: cloudy urine; crawling or tingling sensation of the skin; diarrhea ; faintness (particularly after missing meals); headache; increased skin color; irritability; itching ; joint pain; loss of appetite (anorexia ); numbness or weakness in arms, hands, legs, or feet; stinging sensation on skin; swelling on skin; tenderness of the palms and the soles; nausea and vomiting ; and becoming easily tired.

Less common side effects may include: extreme fatigue or weakness; increased sensitivity of eyes to light; changes in or loss of vision; watery eyes; swelling around eyes; ulcers or sores in mouth; as well as painful and tender glands in the neck, armpits, or groin.

Side effects that may occur rarely include:

cold and clammy skin
convulsions
decreased blood pressure
difficulty breathing
fever and sore throat
fever with or without chills
increased heartbeat
loss of consciousness
pale skin
pinpoint red spots on skin
red, thickened, or scaly skin
swelling and/or tenderness in upper abdominal or stomach area
swollen and/or painful glands
unusual bleeding or bruising
unusual fatigue or weakness
yellow discoloration of the eyes or skin

Some patients may experience other side effects not listed above. Patients experiencing any other side effects should check with the attending physician.

Interactions

Drug interaction information is not readily available for suramin. However, as with any treatment, patients should alert their doctor to any prescription, over-the-counter, or herbal remedies they are taking in order to avoid possible drug interactions.

Crystal Heather Kaczkowski, MSc.

KEY TERMS

Antagonist

—A drug that binds to a cellular receptor for a hormone, neurotransmitter, or another drug. Antagonists block the action of the substance without producing any physiologic effect itself.

Antineoplastic

—Antineoplastic therapy is a regimen of chemotherapy aimed at destroying malignant cells using a variety of agents that directly affect cellular growth and development.

Antiprotozoal

—An agent destructive to protozoa.

Anthelmintic

—An agent destructive to worms. Many anthelmintic drugs are toxic and should be given with care; the patient should be observed carefully for toxic effects after the drug is given.

Clinical trials

—Highly regulated and carefully controlled patient studies, where either new drugs to treat cancer or novel methods of treatment are investigated.

DNA

—Deoxyribonucleic acid. Genetic information carried in chromosomes.

Growth factors

—Growth factors or human growth factors are compounds made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory by genetic engineering and are used in biological therapy. Growth factors are significant because they can induce angiogenesis, the formation of blood vessels around a tumor. These growth factors also encourage cell proliferation, differentiation, and migration on the surfaces of the endothelial cells.