Medication Summary
Most ophthalmologists defer the administration of systemic chemotherapeutic agents to chemotherapists or oncologists. The medical therapy for disseminated Kaposi sarcoma consists of either Adriamycin, bleomycin sulfate, and vinblastine sulfate (ABV) combination or liposomal daunorubicin alone. [35] Liposomal doxorubicin is usually reserved for those patients who fail ABV combination or who are intolerant to ABV therapy. [36] Other second-line therapies include the use of paclitaxel [37] and interferon alfa-n3.
Antineoplastics
Class Summary
These agents inhibit cell growth and proliferation.
Vinblastine sulfate (Velban)
Alkaloid extract of Catharanthus roseus. FDA indications for use of vinblastine are Kaposi sarcoma, choriocarcinoma, histiocytosis X, lymphocytic lymphoma, mycosis fungoides, breast carcinoma, and testicular carcinoma. Mechanism of action is to arrest growing cells in metaphase by inhibiting formation of microtubule assembly during spindle formation. For treatment of Kaposi sarcoma, ABV is conventional combination treatment used. Major route of elimination is through excretion. A small portion is eliminated through urine. Main route of administration is IV.
Bleomycin sulfate (Blenoxane)
Cytotoxic glycopeptide extracted from a strain of Streptomyces verticillus. Commonly used in combination with Adriamycin and vinblastine. Inhibits DNA, RNA, and protein synthesis. Major route of elimination is through urine. Serum concentrations may increase in patients with poor creatinine clearance.
Doxorubicin hydrochloride (Adriamycin, Doxil)
Cytotoxic anthracycline extracted from Streptomyces peucetius. Not FDA approved for the treatment of Kaposi sarcoma but often used in combination with bleomycin and vinblastine.
Mechanism of action is by intercalation of anthracycline with DNA. Subsequently, this blocks DNA and RNA polymerases, resulting in the inhibition of cell growth and proliferation. Major route of elimination is via biliary excretion.
Daunorubicin citrate liposome (DaunoXome)
Anthracycline antibiotic extracted from S peucetius. Indicated for treatment of Kaposi sarcoma. Liposomal version of daunorubicin greatly enhances functional characteristics of the treatment by decreasing plasma clearance and a smaller volume of distribution. Characteristics translate into longer drug exposure. Daunorubicin is a first-line drug for advanced HIV-Kaposi sarcoma. Not recommended for mild involvement.
Paclitaxel (Taxol)
Extract of Taxus baccata. Indicated for second-line treatment of AIDS-related Kaposi sarcoma. Mechanism of action is to promote polymerization of microtubules and to inhibit depolymerization. Prevention of microtubule dynamics results in the inability of the cell to undergo mitosis. Major route of elimination is through hepatic clearance. All patients should be premedicated with dexamethasone 10 mg PO 12 h before treatment, diphenhydramine 50 mg IV 30 min prior to treatment, and cimetidine or ranitidine IV 30 min before treatment.
Interferons
Class Summary
These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alfa, beta, and gamma interferons may be given topically, systemically, and intralesionally.
Interferon alfa-2a (Roferon A), alfa-2b (Intron A), alfa-n3 (Alferon N)
Derived from pooled units of human leukocytes induced by Sendai virus. Human sources of leukocytes are screened carefully for infectious agents (Sendai virus, HIV-1, HTLV-I, HBV, HSV-1, CMV, and EBV).
FDA indication is for condyloma acuminata. Off-label uses include bladder carcinoma, ovarian epithelial carcinoma, renal carcinoma, chronic active hepatitis, AIDS-related Kaposi sarcoma, chronic myelocytic leukemia, hairy cell leukemia, non-Hodgkin lymphoma, malignant melanoma, multiple myeloma, mycosis fungoides, laryngeal papillomatosis, essential thrombocytosis, and carcinoid tumors.
Interferons are secreted normally by cells in response to viral infections. Binding of interferon to receptors initiates of cascade of events that ultimately involves inhibition of viral replication, suppression of mitosis, and other enhancements to the immune system.
Dose of interferon alfa will vary depending on type and brand chosen. SC route is recommended in those with coagulopathies.
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Section of eyelid with Kaposi sarcoma lesion under high magnification. This tissue section demonstrates increased angiogenesis and spindle-shaped cells. Courtesy of Ben Glasgow, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
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Section of eyelid with Kaposi sarcoma lesion under high magnification. This tissue section demonstrates endothelium-lined vascular channels and proliferation of spindle-shaped cells. Increased angiogenesis with erythrocyte extravasation is observed. Courtesy of Ben Glasgow, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
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The inferior conjunctiva is involved more commonly than the superior conjunctiva in Kaposi sarcoma. Courtesy of Gary N Holland, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
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Kaposi sarcoma involvement of the eyelid. Courtesy of Gary N Holland, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
