Dermatologic Manifestations of Kaposi Sarcoma Medication

Updated: Mar 30, 2020
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
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Medication

Medication Summary

The authors' preference often is the Klein [76] regimen of weekly outpatient intravenous vinblastine titered against white cell count levels to avoid falling below 4000/µL. The authors recommend intralesional injections of vinblastine for persistent cutaneous nodules and intraarterial vinblastine in certain settings for locally aggressive Kaposi sarcoma (KS). Systemic vinblastine (3.5-10 mg IV weekly with, at times, 1 intralesional injection of 0.1 mg) usually is best for both the patient with classic Kaposi sarcoma and, occasionally, patients with KS-AIDS. Treatment of classic Kaposi sarcoma may also be accomplished with topical imiquimod. [77] Limited experience in Kaposi sarcoma in renal transplant recipients suggested it may be beneficial in at least some of them. [78]

Although the authors prefer low-dose vinblastine, a number of other chemotherapeutic agents may be effective. Drugs with proven efficiency include vincristine, vinblastine, dacarbazine, doxorubicin, and actinomycin D. Alkylating agents (eg, cyclophosphamide, chlorambucil, bleomycin, doxorubicin, etoposide) also may be of value. Multiagent intravenous chemotherapy, rather than single agent usage, is preferred by some for disseminated aggressive Kaposi sarcoma. No particular combination regimen has been established yet. The combination of doxorubicin, bleomycin, vinblastine, and dacarbazine may be effective.

Alternating vincristine and vinblastine in patients with KS-AIDS can be both effective and well tolerated, but leukopenia and a propensity to opportunistic infections makes aggressive chemotherapy difficult. Patients with KS-AIDS usually succumb either to disseminated Kaposi sarcoma or to an intervening opportunistic infection within 3 years of diagnosis, regardless of the form of therapy (except with HAART therapy). All of these therapies (except low-dose vinblastine) are significantly immunosuppressive and, perhaps, accelerate the disease. Combining chemotherapy for Kaposi sarcoma with chemotherapy for HIV is an attractive option. Interferon also may be used in this way. Thus, the combination of zidovudine, interferon, and low-dose intravenous vinblastine may be used for patients with KS-AIDS.

Experimental treatments for Kaposi sarcoma and HHV-8 infections are myriad. Many come under the rubric of immunotherapy, pioneered for Kaposi sarcoma by Klein in the early 1960s. Other agents (in addition to interferon) used for immunomodulation include bovine-thymic extracts, thymosin, Imreg-l, thalidomide, endothelial growth factor inhibitor (SU5416), human chorionic gonadotropin, isoprinosine, thymopoietin, monoclonal antibodies to T-suppressor (T8) cells, BCG vaccine, cord factor, and topically administered halofuginone, an angiogenesis inhibitor that inhibits collagen type-I and matrix metalloproteinases (MMPs). [79]  There may be a role for checkpoint inhibitors. [80]

The value of recombinant interferon alfa and other modalities may depend on the pretreatment immune status of the patient as the best predictor of response. The degree of reduction in the helper-inducer T-cell (T4) subpopulation as manifested in the T4:T8 ratio may correlate highest with prognosis and be a good measure of immune status for this purpose. Thalidomide therapy may be of value in non-AIDS–related Kaposi sarcoma; in 2 of 3 patients, complete remission was achieved after 12 months of treatment. [81]

In iatrogenic Kaposi sarcoma, cessation of immunosuppressive therapy may be the most effective treatment. Patients on immunosuppressive therapy, specifically corticosteroids and cytotoxic drugs, may have partial or complete regression when therapy is discontinued. If possible, immunosuppressive medication doses should be reduced or discontinued before beginning specific therapy for iatrogenic Kaposi sarcoma. Sirolimus has the advantage of decreased risk of malignancies, including Kaposi sarcoma, associated with its use compared with other immunosuppressants, namely calcineurin inhibitors, and possibly Kaposi sarcoma regression. [82, 83] Everolimus may offer similar advantages. [84]

In some patients, KS-AIDS may resolve clinically with the use of HAART. Resolution of conjunctival Kaposi sarcoma after use of HAART alone has been described. [85] Antiviral therapy with foscarnet may not only reduce progression of Kaposi sarcoma in patients, but may lower its occurrence substantially in patients with HIV disease.

Patients with KS-AIDS, the most common tumor in Zimbabwe, were randomized and evaluated for the effectiveness of supportive care versus 3 intervention approaches, namely oral etoposide, a 3-drug combination, and radiotherapy, using quality of life as the primary measure of success. [86] No patient used antiretroviral therapy. Oral etoposide resulted in a significantly better quality of life and may represent a pragmatic approach to treating epidemic Kaposi sarcoma in an environment where antiretroviral drugs are not universally available.

Paclitaxel and pegylated liposomal doxorubicin were compared in a randomized trial evaluating their efficacy and toxicity. [87] Treatment with both produced significant improvements in pain and swelling in patients with advanced, symptomatic, HIV-associated Kaposi sarcoma. Three fourths of patients had also received highly active antiretroviral therapy.

Antiretroviral therapy for childhood HIV-associated Kaposi sarcoma is not always possible in resource-poor areas. Special recommendations exist for use where only minimal requirements for treatment are available. [88] Randomized controlled studies of chemotherapy for Kaposi sarcoma in children are lacking.

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Chemotherapy agents

Class Summary

Chemotherapy agents inhibit cell growth and proliferation. Vincristine 2 mg IV alternating with vinblastine 0.1 mg/kg IV qwk is effective. Doxorubicin, an anthracycline, is used effectively as ABV combination (doxorubicin A=anthracycline [20 mg/m2 IV], B=bleomycin [10 U/m2 IV], V=vincristine [1.4 mg/m2 IV q2wk]). The combination may produce alopecia, neuropathy, neutropenia, nausea and vomiting, oral erosions, or palmoplantar erythrodysesthesia.

Vinblastine (Alkaban-AQ, Velban)

Vinblastine is an important vinca alkaloid, which is the salt of a common flowering herb, the periwinkle Vinca rosea. It inhibits microtubule formation, which, in turn, disrupts the formation of the mitotic spindle, causing cell proliferation to arrest at metaphase.

Vincristine (Oncovin, Vincasar PFS)

Vincristine is the salt of a common flowering herb, the periwinkle Vinca rosea. Its mechanism of action is uncertain. It may involve a decrease in reticuloendothelial cell function or an increase in platelet production.

Bleomycin (Blenoxane)

Bleomycin is a mixture of cytotoxic glycopeptide antibiotics isolated from a strain of Streptomyces verticillus and freely soluble in water. It is a glycopeptide antibiotic that inhibits DNA synthesis. It is used for palliative measures in the management of several neoplasms.

Doxorubicin (Adriamycin, Rubex)

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var caesius. It inhibits topoisomerase II and produces free radicals, which may cause the destruction of DNA. The combination of these 2 events can in turn inhibit the growth of neoplastic cells.

Daunorubicin (Cerubidine, DaunoXome)

Daunorubicin inhibits DNA and RNA synthesis by intercalating between DNA base pairs.

Paclitaxel (Taxol)

Paclitaxel's mechanisms of action are tubulin polymerization and microtubule stabilization.

Interferon alfa 2b (Interferon alfa-2b, Intron A)

Interferon alfa-2b is a protein product manufactured by recombinant DNA technology. The mechanism of antitumor activity is not understood clearly; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles. It is an effective option for patients with more extensive cutaneous disease that is not rapidly progressive in whom no need exists for a rapid reduction in lesions and in whom overall functional status is relatively good.

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Retinoids

Class Summary

Retinoids decrease cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for malignant degeneration. They modulate keratinocyte differentiation and have been shown to reduce the risk of skin cancer formation in renal transplantation patients.

Alitretinoin topical

Alitretinoin topical is a 0.1% gel. It is a topical treatment for cutaneous lesions. Alitretinoin is a naturally occurring endogenous retinoid. It inhibits the growth of Kaposi sarcoma by binding to retinoid receptors.

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Antiviral agents

Class Summary

Antiviral agents are active against HHV-8 and represent an important potential intervention and prevention option.

Foscarnet (Foscavir)

Use of this medication appears to be linked to a decreased risk of developing Kaposi sarcoma. Foscarnet is an organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. It inhibits viral replication at pyrophosphate-binding site on virus-specific DNA polymerases.

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