This study shows that low-dose paclitaxel proved to be effective and well tolerated in patients with aggressive refractory cKS, controlling the aggressiveness of the disease. The treatment can be repeated with good response.

Lymphedema of the lower extremities is a frequent complication of Kaposi's sarcoma (KS). Compressive therapy is the basis of treatment for lymphatic disorders, but to the authors' knowledge, there are no controlled trials to evaluate its effectiveness in KS-related lymphedema. Sixty-five patients with classic KS-associated lymphedema limited to below the knee were studied. Fifty patients received below-knee elastic stockings, whereas the remaining 15 did not use any compressive device. Among treated patients, 60% (30/50) experienced a limb volume reduction, while 40% (20/50) had an increase of limb volume. In contrast, all patients (15/15) of the untreated group had an increase of limb volume. No correlation between lymphedema reduction and systemic or local chemotherapy was observed, supporting compressive therapy as the major strategy for the treatment of this condition. Our results suggest that elastic stockings may be important tools for the management of lymphedema associated to classic KS.

Intralesional vincristine is an effective and safe treatment for nodular lesions in classic Kaposi sarcoma and can be recommended as first-line therapy in initial stages and as support therapy in advanced stages.

Background: Several drugs are active in aggressive classical Kaposi’s sarcoma (CKS); chemotherapeutic agents with fewer side-effects, more rapid response and able to overcome resistance to previous treatment are advisable when treating patients in a second line. Gemcitabine, an analogue of deoxycytidine with cytotoxic activity in the treatment of solid tumours, has been found to have no serious side-effects. Objective: To evaluate the usefulness of treating patients affected by aggressive CKS with gemcytabine. Methods: Twelve patients with a recurrent aggressive form of CKS previously treated with chemotherapy were treated with gemcitabine. The drug was administered intravenously at the dose of 1.2 g/week for 2 weeks, followed by a 1-week interval, until maximal response was reached. Objective responses and toxicity were evaluated according to WHO criteria. Results: Eleven evaluable patients achieved an objective response: CR in 1/11 and PR in 10/11. Toxicity was limited. Conclusion: This study shows the usefulness of treating patients affected with aggressive CKS with gemcitabine, in order to obtain control of the disease and to reduce the related symptoms as well as to overcome a possible resistance to previous treatments.

D6 is an atypical chemokine receptor acting as a decoy and scavenger for inflammatory CC chemokines expressed in lymphatic endothelial cells. Here, we report that D6 is expressed in Kaposi sarcoma (KS), a tumor ontogenetically related to the lymphatic endothelium. Both in human tumors and in an experimental model, D6 expression levels were inversely correlated with tumor aggressiveness and increased infiltration of proangiogenic macrophages. Inhibition of monocyte recruitment reduced the growth of tumors, while adoptive transfer of wildtype, but not CCR2 À/À macrophages, increased the growth rate of D6-competent neoplasms. In the KS model with the B-Raf V600E-activating mutation, inhibition of B-Raf or the downstream ERK pathway induced D6 expression; in progressing human KS tumors, the activation of ERK correlates with reduced levels of D6 expression. These results indicate that activation of the K-Ras-B-Raf-ERK pathway during KS progression downregulates D6 expression, which unleashes chemokine-mediated macrophage recruitment and their acquisition of an M2-like phenotype supporting angiogenesis and tumor growth. Combined targeting of CCR2 and the ERK pathway should be considered as a therapeutic option for patients with KS.

Background. This Phase III trial was performed to compare the roles of oral etoposide and intravenous (i. v.) vinblastine in the treatment of Mediterranean Kaposi's Sarcoma (MEKS) in elderly patients with severe disease (Stages II, Ac/B, III, and IV). Patients and Methods. Sixty‐five patients were randomized to receive either oral etoposide (60 mg/m2 on Days 1–3 during the first course; 60 mg/m2 on Days 1–4 during the second course, and 60 mg/m2 on Days 1–5 during the third course; the courses were recycled every 3 weeks) or an i. v. bolus of vinblastine (3 mg/m2 weekly for 3 weeks, and then 6 mg/m2 every 3 weeks). Results. No significant difference between the two drugs was observed in terms of response rates (etoposide, 73.5% vs. vinblastine, 58%; P = 0.3), duration of response, or survival (median not yet reached at a median followup of 38 months). Side effects of both treatments were limited, although myelotoxicity was more evident in the vinblastine arm. Conclusions. Although it is feasible and well tolerated, the oral administration of etoposide at these doses and in this regimen does not appear superior to vinblastine in the treatment of MEKS. Further evaluation of a more intensive schedule in large cooperative clinical trials is needed to establish the role of this drug in comparison with reference treatments.

Background: Kaposi’s sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi’s sarcoma by confirmational display analysis and polymerase chain reaction. Objective: As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi’s sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease. Methods: By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi’s sarcoma. Results: HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi’s sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I–II disease as opposed to 73.6% of those with stage III–IV. Conclusion: The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi’s sarcoma.

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