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HIV-Associated Malignancies

Epidemiology of HIV and Neoplasias

Definite Association

Kaposi's sarcoma

Non-Hodgkin's Lymphoma

Squamous carcinoma conjunctiva

Probable Association

Hodgkin's disease

Plasmacytoma

Leiomyosarcoma (Pediatric)

Kaposi's sarcoma


Epidemiology

Kaposi's sarcoma (KS) is the most common neoplasm affecting HIV-infected individuals.

Risk greatest in homosexual male population (up to 73,000 fold risk) but high among all HIV risk, lymphoma, Kaposi's sarcoma, Kaposis, malignancies, Hodgkin's disease, Hodgkin, Hodgkins, Hodgins, sarkoma

Impact of HAART highly significant with well-documented decline on incidence of les after 1995. Since 1995, overall oncudence of KS has declined 61% in MACS study.

Pathogenesis

The pathogenesis of KS in HIV-infected patients is complex and may involve infectious and

Confinement to the homosexual male population with recent declining incidence, its occurrence in non-HIV

infected gay men and in female sexual partners of bisexual men all have suggested the possibility of

Laboratory investigations have identified a novel herpesvirus (HHV-8, KSHV) associated with

Clinical presentation and diagnosis

KS in the HIV-infected individual is usually an aggressive and unpredictable mucocutaneous disease.

Palpable, firm, non-tender, cutaneous nodules, ranging from 0.5 to 2 cm in diameter, are frequently observed.

However, early, small, non-palpable lesions, often resembling small ecchymoses, may be

Cutaneous complications of KS

Pain: as lesions progress at any site they may become painful or locally

Diagnosis

Presumptive diagnoses of KS are discouraged. Biopsy is recommended.

Differential diagnosis includes bacillary angiomatosis, cutaneous micobacterial disease, cutaneous fungal disease and angiosarcoma.

Staging

Systems based purely upon tumor bulk are unhelpful.

In addition to tumor bulk important prognostic factors include: level of

Treatment - can be divided into either local therapy or systemic therapy.

Is a systemic disease and requires some form of systemic therapy (could be antiviral)

Local therapy: the appropriate choice for symptomatic local involvement or small lesions which are cosmetically unsightly.

Radiotherapy - generally 800 cGy or equivalent fractionated dose. Electron beam therapy highly

Intralesional vinblastine: used 0.01 mg vinblastine in .1 ml sterile water per lesion. Repeated

Cryotherapy: liquid nitrogen is used and is successful therapy. Also useful for small cosmetically

Topical Therapy: 9-cis retinoic acid (approval pending)

Systemic therapy (chemotherapy): indicated for widespread symptomatic disease, rapidly

Liposomal anthracyclines: First-line therapy for advanced cutaneous or visceral disease.

The doxorubicin, bleomycin, vincristine (ABV) is less commonly employed for patients with

Regimens such as vincristine and bleomycin may be used for less advanced symptomatic disease

Paclitaxel (Toxol): Highly active agent used as second-line therapy in patients refactory initial

Systemic Therapy for AIDS-KS

Single Agent

Agent Dose Reported Response Recommended Use
Vincristine 2 mg/wk 20-59% Rarely used alone, nonmyelosuppressive
Vinblastine 0.5-1 mg/kg/wk 25-30% Rarely used alone
Etoposide 50 mg po qd, alternate weeks or 150 mg/m3 IV qd for 3d q 3-4 wks 36-75% As single agent for prior treatment failure
Adriamycin 20 mg/m2 q OW 53% Rarely used alone
Bleomycin 10-15 u/m2q 2 wks

or

20 mg/m2/d x 3d

65% Nonmyelosuppressive; use if intolerance to other agents
Paclitaxel 100 mg/mq2 2 wks 53% Treatment failures*
Liposomal

Doxorubicin

20 mg/m2 q 2-3 wks 45-74% Single agent

Refractory disease*

Liposomal

Daunorubicin

40 mg/m2 q 2 wks 28-55% Single agent

First line therapy*

Vinorelbine 30 mg/m2 q 2 wks 40% Treatment Failures

*FDA-approved indications


Agents Dose Reported Response Recommended Use
Vincristine/Vinblastine 2 mg alternate

0.1 mg/kg weeks

45% Diffuse, disease, minimally symptomatic
Adriamycin/Bleomycin/

Vincristine

10-20 mg/m2

10 mg/m3 q 14d

2 mg

87% Diffuse symptomatic disease, edema, rapid response desired
Bleomycin/Vincristine 10 mg/m2 q 14d

2 mg

  Diffuse disease, symptomatic, patients with neutropenia or poor bone marrow reserve

INTERFERON ALFA

Interferon

An active regimen for treating Kaposi's sarcoma.

Drag requires some level of intact immune function in order to achieve response. Those with

Therapeutic complications

Neutropenia: patients with poor bone-marrow reserve may be treated with bleomycin and vincristine, neither of which are myelosuppressive.

Investigational Agents

Investigational approaches at present are pathogenesis-based:

Angiogenesis inhibitors: rPF4, Tecogalan, TNP470

Retinoids: All trans-RA, 9-cis-RA, Liarozole

Cytokine inhibitors: IL4-, pentoxifylline, SU101

Antivirals: Foscarnet, Protease Inhibitors

Antiretroviral Therapy

KS responses have been observed to protease inhibitor or combination antiviral therapies in

HIV-associated lymphoma

Epidemiology

B-cell lymphoma occurs in between 5 and 10% of individuals with HIV infection. The incidence of lymphoma in this population has 'been rising and may reflect the prolongation of survival due to the use of effective antiretroviral therapy and infection prophylaxis.

Etiology

A. Etiology is unknown. Unlike transplant-associated NHL, Epstein-Barr virus has not been shown to be associated with a majority of systemic lymphomas. However, EBV DNA is found in

B. Other similarities exist with transplant-associated NHL. Polyclonal lymphomas have been

C. In vitro evidence suggests a role for interleukins 6 and 10 in pathogenesis. Inhibition of these

D. Body-cavity based lymphomas associated with HHV-8.

Pathology

HIV-associated non-Hodgkin's lymphomas are virtually all of B-cell origin. Most are

Systemic lymphomas present in individuals with a variety of levels of immune function (median approx 100/mm3). Seventy-five percent have CD4>50/mm3 . Most present with extranodal

Treatment

Treatment is frequently complicated by the occurrence of opportunistic infection and by the presence of poor bone marrow reserve both of which result in a decrease in the chemotherapy

Approaches to therapy that have been used include reduced-dose chemotherapeutic regimens (low-dose mBACOD or CHOP) and the use of more standard dose regimens with the adjunctive use of a hematopoietic growth factor (GM-CSF or G-CSF). Both colony stimulating feeders are effective means of reducing chemotherapy-associated myelosuppression.

Low-dose mBACOD:

In a non-randomized clinicaltrial this treatment regimen is associated with similar response and

Agent Dose Day
Cyclophosphamide 300 mg/m2, IV 1
Doxorubicin 25 mg/m2, IV 1
Bleomycin 4 mg/m2 , IV 1
Vincristine 2 mg, IV 1
Dexamethasone 3 mg/m2 , po 1-5
Methotrexate 500 mg/m2, IV

Folinic acid rescue

25 mg q 6h x 6 beginning 24

hours after completion of MTX

15

2. Aggressive Chemotherapy

a. Historically associated with higher risk of death due to opportunistic infection better tolerated in

b. Unclear whether longer survival observed in one study (LNH-84) due to

c. Myeloid growth factors (G-CSF, GM-CSF) have been shown to reduce hematologic toxicity

4. No survival difference. Most deaths due to opportunistic infection.

H. Meningeal prophylaxis (intrathecal MTX or cytosine arabinoside) clearly indicated for those

with positive bone marrow, small noncleaved histology and those with paranasal or epidural

I. Pneumocystis carinii prophylaxis is an important adjunct to regardless of CD4 count. Trimethoprim-sulfamethoxazole, dapsone, or inhaled pentamidine may be used.

J. Infusional cyclophosphamide, doxorubicin, etoposide (CDE) (Investigational)

1. Associated with similar complete response rate as with other regimens (60%).

2. Long survival reported (median 18 months) in pilot study.

Anogenital Neoplasia

I. Nomenclature

A. C(A) IN = Cervical (Anal) Intraepithelial neoplasia

B. SIL = Squamous intraepithelial lesion

C. ASCUS = Atypical squamous cells of undetermined significance

D. CIN1 (mild dysplasia) - LSIL

D. CIN2 (moderate dysplasia) - HSIL