AIDS-related Kaposi's Sarcoma Research Articles

AIDS‐related Kaposi's sarcoma in Brazil: trends and geopolitical distribution

AIDS-related Kaposi's sarcoma (KS) is a unique model of the relationship between viral infection, immunity, environmental, and genetic factors in viral cancers. The goal was to determine the distribution of KS cases among Brazilian geopolitical regions, looking at the ecological relationship with median CD4 cell count. Ecological study using Brazilian National Diseases Reporting Databases: 1982-2009. Subjects ≥ 13 years of age who have KS cited in their AIDS reporting form were selected, and demographic and HIV exposure data were collected. We found 11,731 KS cases in the period, with a prevalence of 2.4% among AIDS cases; 88% were male, and 68% lived in the Southeast region, which accounted for 59% of AIDS cases. The regional and national prevalence trends were similar, although the highest proportion among women was found in the North region, which has the lowest number of both AIDS and KS cases. Heterosexual transmission accounted for 87% of HIV among women compared to 18% among men. Fifty-seven percent of all KS cases were diagnosed before antiretroviral therapy (ART). Injection drug use accounted for 11% of KS cases. Median survival was 472 days before the ART era and 1482 after it (P < 0.001). Median CD4 counts increased in all regions in the period as ART coverage expanded, and a resulting correlating decline in KS cases was observed. Prevalence of KS declined after the introduction of ART in all regions of Brazil, suggesting individual protection conveyed by ART.

Small Bowel Kaposiʼs Sarcoma: An Unusual Cause of GI Bleeding

Purpose: A 34-year-old previously healthy man presented with 1 week of melena and new right sided hemiplegia for 1 month. Initial hemoglobin was 6 g/dL from a baseline of 13.5 g/dL two years prior. Brain MRI showed two ring enhancing lesions in the left cortex and cerebellum suspicious for toxoplasmosis. An HIV antibody test was positive, with a CD4 count of 1. An upper endoscopy was performed and showed white adherent material in the esophagus (biopsy pathology positive for candidiasis), gastric erythema and normal duodenum without a bleeding source. Colonoscopy showed normal terminal ileal and colonic mucosa. A capsule endoscopy demonstrated a raised medium-sized submucosal erythematous mass in the mid-jejunum, suspicious for Kaposi's sarcoma (KS). A detailed skin exam yielded a violaceous plaque on the abdomen, with biopsy pathology diagnostic of KS. The patient was started on antiretroviral therapy (ART) and treatment for cerebral toxoplasmosis, with no further episodes of melena. KS is a vascular tumor that is associated with human herpesvirus 8 and is the most common tumor arising in HIV-infected persons. Its prevalence is increased with lower CD4 counts. KS was over 20,000 times more common in persons with AIDS than in the general population prior to the widespread use of highly active antiretroviral therapy (HAART), and the incidence has declined substantially since that time. Although KS can involve virtually any site in the body, cutaneous disease is most common and is the usual initial presentation for KS. The most frequent sites of noncutaneous disease are the oral cavity, gastrointestinal tract (most commonly the small intestine) and respiratory system. Prior to widespread ART, the gastrointestinal tract was involved in approximately 40% of patients with KS at initial diagnosis, and in up to 80% at autopsy. However, visceral involvement as the initial manifestation of KS in the HAART era is relatively uncommon. GI lesions may be asymptomatic or cause weight loss, abdominal pain, nausea and vomiting, upper or lower gastrointestinal bleeding, malabsorption, intestinal obstruction or diarrhea. On endoscopy, KS lesions are easily recognized as hemorrhagic nodules that can appear anywhere along the GI tract. In the HAART era the incidence of AIDS-related KS has dramatically decreased to less than 10% of the incidence reported in the pre-HAART era, but it is still recognized as a primary AIDS-defining illness that can lead to significant morbidity. Rarely, visceral KS can present as occult or gross GI bleeding. In persons with underlying AIDS presenting with anemia and/or GI bleeding, it is important for physicians to consider intestinal KS as a possible etiology.

Pegylated Liposomal Doxorubicin: A Guide to Its Use in Various Malignancies

Pegylated liposomal doxorubicin (Caelyx(®) [EU], Doxil(®) [USA]) represents an improved formulation of conventional doxorubicin, with reduced cardiotoxicity and an improved pharmacokinetic profile. As shown by evidence from clinical trials, intravenous pegylated liposomal doxorubicin is a useful option in the treatment of various malignancies, including metastatic breast cancer, ovarian cancer, multiple myeloma, and AIDS-related Kaposi sarcoma. It has a favourable safety profile relative to conventional doxorubicin and other available chemotherapy agents.

Synergy between Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 and HIV-1 Nef protein in promotion of angiogenesis and oncogenesis: role of the AKT signaling pathway

Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma (KS), which is the most common AIDS-associated malignancy. KS is characterized by neovascularization and spindle cell proliferation. The interaction between HIV-1 and KSHV has a central role in promoting the aggressive manifestations of KS in AIDS patients; however, the pathogenesis underlying AIDS-related KS (AIDS-KS) remains unknown. Herein, we examined the potential of HIV-1 negative factor (Nef) to impact KSHV viral interleukin-6 (vIL-6)-induced angiogenesis and tumorigenesis. In vitro experiments showed that exogenous Nef penetrated vIL-6-expressing endothelial cells. Both internalized and ectopic expression of Nef in endothelial cells and fibroblasts synergized with vIL-6 to promote vascular tube formation and cell proliferation. Using a chicken chorioallantoic membrane (CAM) model, we demonstrated that Nef synergistically promotes vIL-6-induced angiogenesis and tumorigenesis. Animal experiments further showed that Nef facilitates vIL-6-induced angiogenesis and tumor formation in athymic nu/nu mice. Mechanistic studies indicated that Nef synergizes with vIL-6 to enhance angiogenesis and tumorigenesis by activating the AKT pathway in the CAM model, as well as nude mice. LY294002, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), significantly impaired the ability of Nef to promote vIL-6-induced tumorigenesis in an allograft model of nude mice. Our data provide first-line evidence that Nef may contribute to the pathogenesis underlying AIDS-KS in synergy with vIL-6. These novel findings also suggest that targeting the PI3K/AKT signal may be a potentially effective therapeutic approach in AIDS-KS patients.

HIV-1 Tat Promotes Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) vIL-6-Induced Angiogenesis and Tumorigenesis by Regulating PI3K/PTEN/AKT/GSK-3β Signaling Pathway

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is etiologically associated with KS, the most common AIDS-related malignancy. KS is characterized by vast angiogenesis and hyperproliferative spindle cells. We have previously reported that HIV-1 Tat can trigger KSHV reactivation and accelerate Kaposin A-induced tumorigenesis. Here, we explored Tat promotion of KSHV vIL-6-induced angiogenesis and tumorigenesis. Tat promotes vIL-6-induced cell proliferation, cellular transformation, vascular tube formation and VEGF production in culture. Tat enhances vIL-6-induced angiogenesis and tumorigenesis of fibroblasts and human endothelial cells in a chicken chorioallantoic membrane (CAM) model. In an allograft model, Tat promotes vIL-6-induced tumorigenesis and expression of CD31, CD34, SMA, VEGF, b-FGF, and cyclin D1. Mechanistic studies indicated Tat activates PI3K and AKT, and inactivates PTEN and GSK-3β in vIL-6 expressing cells. LY294002, a specific inhibitor of PI3K, effectively impaired Tat’s promotion of vIL-6-induced tumorigenesis. Together, these results provide the first evidence that Tat might contribute to KS pathogenesis by synergizing with vIL-6, and identify PI3K/AKT pathway as a potential therapeutic target in AIDS-related KS patients.

Clinical Application of Drug Delivery Systems in Cancer Chemotherapy: Review of the Efficacy and Side Effects of Approved Drugs

In recent years, drug delivery systems (DDS) have been developed, along with anticancer agents for those systems based on the concept of achieving a better clinical response and tolerability. Several clinical trials have shown that these drugs have better clinical effects in the treatment of many cancers, leading to their expanded indications. Liposomal doxorubicin is one DDS agent used to treat AIDS-related Kaposi's sarcoma and ovarian cancer in Japan. In addition to those two indications, the Food and Drug Administration (FDA) approved this drug for the treatment of multiple myeloma in 2007. Another DDS agent approved in Japan is nanoparticle albumin-bound paclitaxel, which has been used in the treatment of breast cancer. Most recently, this drug has been approved for the treatment of non-small cell lung cancer in the U.S.A. Although these DDS agents appear to be less toxic than conventional drugs, DDS-specific side effects such as various skin reactions, hypersensitivity reaction, and peripheral neuropathy sometimes occur. Therefore, medical staff must understand DDS anticancer agents fully, including characteristic side effects, to achieve the desired clinical outcomes.

AIDS related Kaposi sarcoma: 103 cases in dermatology in Lomé (Togo)

The purpose of this study was to describe the epidemiological and clinical profile and the treatment and natural history of AIDS-related Kaposi sarcoma in 3 major dermatology departments in Lomé (Togo). This retrospective, descriptive study was based on the records of patients with AIDS-related Kaposi sarcoma from January 2005 through October 2011. During the study period, 157 patients were treated in the dermatology departments for Kaposi sarcoma. HIV serology was positive for 103 (89.6%) of the 115 patients tested. Seventy-nine patients were known to be HIV-positive before the consultation, while Kaposi sarcoma was the circumstance of discovery of the HIV infection for 24. The average age of the 103 patients was 36.7±14.9 years and the sex-ratio (M/F) was 1.1. The main locations of the lesions were the lower limbs (n = 76), mucosa (n = 53), trunk (n = 38) and upper limbs (n = 17). The average CD4-cell count was 226±168 cells/mm(3). The main antiretroviral protocol used was stavudine/lamivudine/nevirapine (70 cases). Besides the antiretroviral treatment, chemotherapy was prescribed, with vinblastine for 17 patients, bleomycin for 5, and doxorubicin for one. For financial reasons, 80 other patients did not receive chemotherapy and were lost to follow-up after an average duration of 3 months. At 5 months, the rate of complete remission was 21.1%, partial remission 21.1%, and failure 57.8%. Side effects were dominated by hematologic and nervous complications. Our study highlighted a high prevalence of AIDS-related Kaposi sarcoma in dermatology departments in Lomé, with a tendency to gender equality. It also shows the difficulties of access to chemotherapy for most patients and the poor efficacy of chemotherapy.

Kaposiʼs Sarcoma

A 56 y/o HIV-infected African American male presented with non-bloody diarrhea for 3 days. He also complained of diffuse abdominal pain, worse in the epigastric area, for the past 4 months and associated with nausea and intermittent non-bloody, non-bilious vomiting, especially after eating solid food. He admits to 33 pounds weight loss over 6 months. He denies any fever or chills, any rash or skin lesions. His HIV risk factor was intravenous drug use. His CD4 count was 46 cells/mm3 and HIV RNA was 123,664/ml. He was non-compliant with HAART. Co-morbid conditions included polysubstance abuse and HCV infection. There was moderate epigastric tenderness on physical examination. Laboratory studies showed anemia, stool studies were negative for enteric pathogens, but stool occult blood was positive. A CT scan of abdomen with contrast showed prominent lymph nodes in the paraesophageal and retroperitoneal areas. An EGD showed a large, fungating, circumferential mass with no bleeding in the gastric antrum. Biopsies were performed and the pathologic diagnosis was Kaposi's sarcoma (KS). Immunohistochemical stains for HHV-8 were positive.Figure: [648]Conclusion: In the pre-HAART era, the prevalence of KS was over 20,000 times higher in patients with AIDS than in the general population. The use of HAART has led to a decline in the prevalence of AIDS-related KS, but the benefit is limited to patients who adhere to therapy. Skin involvement is characteristic but extracutaneous spread is common, particularly to the oral cavity, GI tract, and respiratory tract. Before the HAART era, GI tract involvement was 40% and occurred without cutaneous disease in many cases. Patient may be asymptomatic or can have weight loss, nausea, vomiting, abdominal pain, malabsorption, GI hemorrhage, intestinal obstruction, or diarrhea. The visual lesions are characteristic and the diagnosis can be confirmed on histopathology. The staging system, developed by AIDS Clinical Trials Group (ACTG) of the National Institute of Health, which consists of 3 parameters: extent of tumor, Immune status and severity of systemic illness, divides patients into good and poor risk categories. Treatment depends on the presence or absence of clinical symptoms as well as on CD4 count, HIV viral load and presence of HHV-8. For symptomatic patients, the treatment is chemotherapy with liposomal anthracyclines as well as antiretroviral therapy to optimize cellular immune function.

Update on Vascular Neoplasms

This article provides an update on vascular neoplasms. New immunohistochemical markers for the diagnosis of vascular neoplasms tumor 1, infantile hemangiomas, myopericytomas, perivascular epithelial cell tumors, acquired elastotic hemangiomas, vascular proliferations in radiated skin, and new histopathologic variants of AIDS-related Kaposi sarcoma are explored.

Poor immune status and systemic disease are independently associated with mortality in AIDS-related Kaposi Sarcoma in Nigeria

Material and methods We collected epidemiologic, clinical, staging and survival data for 357 patients with a diagnosis of AIDS-KS enrolling for HIV-care at the Jos University Teaching Hospital. Patients were staged according to the AIDS Clinical Trials Group (ACTG) criteria, which are based on the evaluation of tumor extension (T), CD4+ cell count (I), and patient’s systemic status (S), stratified by good (0) versus poor (1) risk. Information on survival was obtained through an active follow-up on verification of vital status of the patients. Survival analysis was computed by the KaplanMeier method, and the log-rank test was used to test the difference between subgroups.

The prevalence of HIV-1 DNA in AIDS-related lymphoma and Kaposi Sarcoma throughout the AIDS epidemic

Background Chronic inflammation is linked to tumorigenesis for many cancer types and likely contributes to tumor development in the HIV-infected patient population. AIDSrelated lymphoma (ARL) and Kaposi Sarcoma (KS), two AIDS-defining cancers, are associated with the tumor viruses EBV and KSHV, respectively. However, EBV is only detectable in ~40% of ARLs and KSHV alone is not sufficient for KS development. Recent studies have shown that HIV is localized to tumor associated macrophages (TAM), not malignant B cells, in a portion of EBV-negative ARLs suggesting, that HIV infected TAM may play ar ole in tumorigenesis. The goal of this research was to determine the prevalence of HIV+ ARL and KS throughout the AIDS epidemic and examine tumor associated HIV for unique genetic signatures. Material and methods Whole genomic amplified DNA from ARL and KS biopsies was used for quantitative HIV gag gene amplification. The 3’ env-LTR segment of HIV-1 genomes from tumor and non-tumor tissues from two patients that died of ARL were sequenced and Bayesian phylogenies were inferred using BEAST. All specimens were provided by the AIDS and Cancer Specimen Resource. Results Of the 119 ARL and 91 KS biopsies, 45% and 40% contained detectable HIV-1 DNA, respectively. There was a significant decrease in the prevalence of HIV-1 DNA positive ARL and KS cases in the post-HAART era (after 1996; ARL=39%, KS=16.7) as compared to preHAART (ARL=54%, KS=45%). Our data suggest the overall amount of HIV DNA is less in tumor biopsies from the post-HAART era. A subset of ARL contained extremely high levels of HIV-1 DNA (~1 copy/cell). In addition, visceral KS had a higher prevalence of HIV-1 DNA (51.9%) as compared to skin KS (30.7%). HIV sequence evolution analysis of metastatic ARLs revealed that HIV was compartmentalized within sites of lymphoma and was distinct from HIV present in nonlymphoma sites. Conclusions The prevalence of HIV-1 DNA positive ARLs declined in the post-HAART era, but not to the same extent as KS, consistent with the incidence of both tumor types in the post-HAART era. Higher prevalence of HIV-1 DNA in visceral sites of KS and lymphoma specific-HIV sequences in sites of metastatic lymphoma suggests that HIV, especially HIV infected macrophages, may play a role in the pathogenesis of KS and ARL disease progression. Additionally, HIV-infected macrophages are a source of chronic inflammation that may further enhance tumorigenesis. Our data suggest a tumor specific form of HIV may be evolving within individuals who develop ARL.

Epidemiology of classic and AIDS-related Kaposi's sarcoma in the USA: incidence, survival, and geographical distribution from 1975 to 2005

This study aimed to examine trends in incidence, geographical distribution, and survival of classic and AIDS-related Kaposi's sarcoma (KS) in the general US population using Surveillance, Epidemiology, and End Results (SEER) tumour registries with 12 066 patients diagnosed with KS between 1975 and 2005. Although the age-adjusted standardized incidence ratio (SIR) of AIDS-related KS (1·9) during 1980-2005 was not significantly higher than that of classic KS (1·4) during 1975-2005 (P = 0·78), the trends in annual SIR rates revealed distinct patterns. While the SIR for AIDS-related KS declined across all registries from the early 1990s (4·6) to late-1990s (0·3) (P = 0·05), the SIR of classic KS remained relatively steady (1·7). In both forms the SIR of KS was highest in metropolitan areas. The 5-year survival rates for patients with AIDS-related KS improved from 12·1% (1980-1995) to 54% (1996-2005) (P = 0·05). Survival rates for patients with classic KS remained stable, ranging from 75·7% to 88·6% during the 30-year period. These results may reflect improved HIV treatment.

Utility of Immunohistochemical Staining With FLI1, D2-40, CD31, and CD34 in the Diagnosis of Acquired Immunodeficiency Syndrome–Related and Non–Acquired Immunodeficiency Syndrome-Related Kaposi Sarcoma

Kaposi sarcoma (KS) is a vascular tumor frequently associated with advanced human immunodeficiency virus infection, advanced age, or iatrogenic immunosuppression. Immunohistochemistry for CD31 and CD34, and more recently for FLI1 and D2-40, has been used as ancillary diagnostic tests for KS, despite little information regarding the sensitivities and differential staining patterns of the latter 2 markers in the major clinical subtypes and histologic stages of KS. This retrospective study aims to assess the prevalence of the vascular markers D2-40 and FLI1 in the main clinical subgroups and tumor stages of KS. Twenty-four cases of KS (12 acquired immunodeficiency syndrome [AIDS]-related cases and 12 non-AIDS-related cases; 11 nodular-stage and 13 patch/plaque-stage KS) were stained for CD34, CD31, D2-40, and FLI1 by immunohistochemistry. The distribution of immunoreactivity was compared between the clinical subtypes and tumor stages of KS using the Mann-Whitney test. CD31, CD34, D2-40, and FLI1 strongly and diffusely stained tumor cells in 75%, 92%, 67%, and 92% of AIDS-related cases and 58%, 92%, 67%, and 75% of non-AIDS-related cases, respectively. Differences in the proportions of positive cases between AIDS-related and non-AIDS-related cases did not reach statistical significance. No significant staining differences were observed between nodular- and patch/plaque-stage KS either. There are no differences in the distribution of immunohistochemical reactivity for CD31, CD34, D2-40, or FLI1 between AIDS-related and non-AIDS-related KS or between nodular- and patch/plaque-stage KS. All of the markers studied demonstrated high sensitivity in both clinical settings and both stages of tumor progression.

CpG Methylation as a Tool to Characterize Cell-Free Kaposi Sarcoma Herpesvirus DNA

We studied the presence of Kaposi sarcoma herpesvirus sequences in cell-free DNA (cfDNA) isolated from the blood of patients with AIDS-related Kaposi sarcoma (KS) and primary effusion lymphoma (PEL). The use of paramagnetic beads linked to methyl-CpG binding domain protein allowed separation of virion and cell-derived DNA. Only virion DNA was detected in the blood of KS patients, whereas cell-derived DNA was detected in a patient with AIDS-related PEL. The difference in the origins of cfDNA in these settings may in part reflect very different proliferative indices in KS and PEL tumor tissue.

Herpes Simplex Virus Type 2 Triggers Reactivation of Kaposi's Sarcoma-Associated Herpesvirus from Latency and Collaborates with HIV-1 Tat

Kaposi's sarcoma-associated herpesvirus (KSHV) infection was necessary but not sufficient for Kaposi's sarcoma (KS) development without other cofactors. Previously, we identified that both human immunodeficiency type 1 (HIV-1) Tat and herpes simplex virus 1 (HSV-1) were important cofactors reactivating KSHV from latency. Here, we further investigated the potential of herpes simplex virus 2 (HSV-2) to influence KSHV replication and examined the role of Tat in this procedure. We demonstrated that HSV-2 was a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV Rta and a luciferase reporter assay testing Rta promoter-driven luciferase activity. Mechanistic studies showed that HSV-2 infection activated nuclear factor-kappa B (NF-κB) signaling pathway. Inhibition of NF-κB pathway enhanced HSV-2-mediated KSHV activation, whereas activation of NF-κB pathway suppressed KSHV replication in HSV-2-infected BCBL-1 cells. Additionally, ectopic expression of Tat enhanced HSV-2-induced KSHV replication. These novel findings suggest a role of HSV-2 in the pathogenesis of KS and provide the first laboratory evidence that Tat may participate HSV-2-mediated KSHV activation, implying the complicated pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS (AIDS-KS) patients.

AIDS-related Gastrointestinal Kaposi Sarcoma in Korea: A Case Report and Review of the Literature

Kaposi sarcoma (KS) is a vascular neoplasm, which is fairly prevalent in acquired immunodeficiency syndrome (AIDS) patients. Mucocutaneous and lymph node involvements are characteristic features of KS in AIDS patients. The involvement of gastrointestinal tract occurs in 40% of KS patients and leads to significant morbidity and mortality. In the highly active antiretroviral therapy (HAART) era, the rate of AIDS related KS has fallen with control of human immunodeficiency virus (HIV) viremia. However, it is still recognized as the primary AIDS-defining illness, and the proportion of AIDS diagnoses made due to KS ranged from 4.1% to 7.5%. In Korea, AIDS-related KS has been report in low rate incidence. Its gastrointestinal involvements are rarely reported. To date, five cases have been recorded in Korea. Herein, we present an additional case of gastrointestinal KS as the AIDS-defining illness and review of the Korean medical literature.

Kaposi Sarcoma in A HIV Positive Nigerian Child: A Case Report.

AIDS-related Kaposi sarcoma is a malignancy thought to arise from endothelial cells. It is the commonest malignancy seen in HIV infected patients. In the USA, it was the initial presentation in 15% of homosexual men. In Africa, it is common in heterosexual adults. Compared to other regions, it is reported to be higher in East Africa. Positivity to human herpes virus 8(HHV8) is known to predate the development of Kaposi sarcoma by 5-10 years. This interval is further shortened in patients who have HIV infection prior to seroconversion to HHV8 positivity. The disease usually develops in HIV infected patients with severe immunodeficiency. Kaposi's sarcoma (KS) is extremely rare among children in the developed countries and was rare in the developing countries prior to the AIDS epidemic. We report here, a 6year old female who presented with severe weight loss, swellings in oropharyngeal region with significant lymphadenopathy in the neck,

Etoposide, vincristine, doxorubicin and dexamethasone (EVAD) combination chemotherapy as second-line treatment for advanced AIDS-related Kaposi’s sarcoma

To evaluate through retrospective analysis the efficacy and toxicity of combination chemotherapy with etoposide, vincristine, doxorubin and dexamethasone (EVAD) as second-line therapy in patients with advanced AIDS-related Kaposi's sarcoma (AIDS-KS) after failure of first-line chemotherapy. Eighty-eight patients with poor-risk AIDS-KS were treated intravenously with combination chemotherapy with EVAD; etoposide at a dose of 100 mg/m(2) on three consecutive days, vincristine 1.4 mg/m(2) with a maximum single dosage of 2.0 mg on day one, doxorubicin 30 mg/m(2) on day one and dexamethasone 40 mg on three consecutive days, with a three week cycle. All eligible patients had relapsed or progressed after prior two to six cycles of combination chemotherapy with doxorubicin, bleomycin and vincristine (ABV) or bleomycin and vincristine (BV). Assessment of the response of all the patients was made. The overall objective response rate was 59.1% (95% CI 48.83-69.37%), with five complete responses and 47 partial responses. Twenty-six cases of stable disease and 10 of progressive disease were observed in the remaining patients. The median follow-up period was 27 months (range 8-52 months). The median time to progression was 6.80 months (95% CI 2.04-11.56 months), and the median overall survival was 14.24 months (95% CI 10.26-18.22 months). Leucopenia was seen in 92.0% of patients, of which 20 patients had grade 3 and 12 had grade 4. Conclusions Combination chemotherapy with EVAD offers a new, active and safe therapeutic approach for the treatment of advanced AIDS-related KS.

Pegylated Liposomal Doxorubicin

Pegylated liposomal doxorubicin (Caelyx™, Doxil®) represents an improved formulation of conventional doxorubicin, with reduced cardiotoxicity and an improved pharmacokinetic profile. This article reviews the efficacy and tolerability of pegylated liposomal doxorubicin in metastatic breast cancer, progressive ovarian cancer, relapsed or refractory multiple myeloma and AIDS-related Kaposi's sarcoma, as well as summarizing its pharmacological properties. In three randomized, open-label, multicentre trials, monotherapy with pegylated liposomal doxorubicin was as effective as doxorubicin or capecitabine in the first-line treatment of metastatic breast cancer, and as effective as vinorelbine or combination mitomycin plus vinblastine in taxane-refractory metastatic breast cancer. Pegylated liposomal doxorubicin alone was as effective as topotecan or gemcitabine alone in patients with progressive ovarian cancer resistant or refractory to platinum- or paclitaxel-based therapy, according to the results of three randomized multicentre trials. In addition, in patients with progressive ovarian cancer who had received prior platinum-based therapy, progression-free survival was significantly longer with pegylated liposomal doxorubicin plus carboplatin than with paclitaxel plus carboplatin, according to the results of a randomized, open-label multicentre trial. Combination therapy with pegylated liposomal doxorubicin plus bortezomib was more effective than bortezomib alone in patients with relapsed or refractory multiple myeloma, according to the results of a randomized, open-label, multinational trial. Randomized multinational trials also demonstrated the efficacy of pegylated liposomal doxorubicin in patients with advanced AIDS-related Kaposi's sarcoma. Pegylated liposomal doxorubicin exhibited a relatively favourable safety profile compared with conventional doxorubicin and other available chemotherapy agents. The most common treatment-related adverse events included myelosuppression, palmar-plantar erythrodysesthesia and stomatitis, although these are manageable with appropriate supportive measures. To conclude, pegylated liposomal doxorubicin is a useful option in the treatment of various malignancies, including metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma.

Classic Kaposi's Sarcoma: A Case Report and Literature Review

Kaposi's Sarcoma (KS) is a rare multifocal spindle cell tumor with four epidemiologic variants: classic KS, African endemic KS, AIDS related KS, and immunosuppressant therapy related KS. Classic KS remains a rare but challenging disease because of its protracted, indolent course. The authors describe a case recently observed in our clinic, emphasizing the clinical management of the disease.