First‐line treatment with paclitaxel for non‐HIV‐related Kaposi sarcoma: experience in 10 cases

DEAR EDITOR, Kaposi sarcoma (KS) is a rare angioproliferative neoplasm caused by infection with human herpesvirus 8. Four epidemiological forms of KS have been characterized: classic KS, endemic KS, iatrogenic KS and AIDS-related KS. In most cases, classic and endemic KS are indolent diseases, for which systemic treatment is unnecessary. However, aggressive forms may develop with visceral involvement or lymphoedema. Chemotherapy is justified for the treatment of these forms, although the age of the patients, many of whom are old, may limit treatment options. In a recent systematic review of the literature, the authors concluded that they could not recommend a particular strategy for patients with KS requiring systemic treatment. The treatment options for such patients include immunotherapy with interferon, or chemotherapy, often with single drugs such as vinblastine, vincristine, bleomycin or oral etoposide, with similar response rates. More aggressive forms of KS may require anthracyclines, either alone or with other drugs. Taxanes have been approved by the US Food and Drug Association as a second-line treatment for AIDS-related KS, following the publication of a limited number of prospective studies highlighting the good responses obtained in this setting. These microtubule-stabilizing agents interfere with KS by inhibiting Bcl-2 antiapoptotic activity. Taxanes have a low toxicity and are therefore suitable for use in the elderly. A few recent studies have reported these drugs to be effective against classic or endemic KS refractory to other types of chemotherapy, and a few individual case reports have suggested that they may also be effective as first-line treatment. We describe here our experience concerning the efficacy and toxicity of paclitaxel as a first-line treatment in aggressive non-HIV-related KS. From 2007 to 2014, 10 patients with non-HIV-related KS (six cases of classic KS and four of endemic KS) received paclitaxel as first-line treatment. The patient characteristics, response to treatment, tolerance and outcome are summarized in Table 1. There were nine men and one woman, and the mean age at KS diagnosis was 66 years. Patients were classified as having stage II–IV disease, according to the Krigel classification. One patient had visceral involvement, characterized by a symptomatic localization on the piriform recess; one patient had inguinal and parailiac lymph node involvement and the other eight patients were treated due to extensive cutaneous disease and the presence of a large lymphoedema. All had functional impairment. Two patients had received local radiotherapy before chemotherapy. None of the other patients had received any prior treatment. The patients underwent intravenous infusions of paclitaxel, at a dose of 80 mg m 2 (n = 2) or 100 mg m 2 (n = 8) every 2 weeks. Treatment was stopped if a stable response had been achieved by the first evaluation (after four to six cycles) or if a serious adverse event occurred. The mean number of taxane infusions per patient was 4 6 (range 1–6). In all of the patients, functional impairment and lymphoedema were found to have improved substantially after as few as two cycles. We report the response according to the AIDS Clinical Trials Group criteria. Treatment was stopped in one patient, during the second infusion, due to a severe systemic allergic reaction, which is a well-known dose-independent adverse event, justifying the administration of prophylactic premedication. Another patient presented an atrioventricular conduction disturbance during the third infusion. The treatment was stopped for safety reasons, and all the necessary cardiological examinations were carried out. The patient did not need a pacemaker. Four patients had episodes of paraesthesia, after the first or second course of treatment. The neuropathy persisted in one patient despite the interruption of the treatment after the third cycle. Treatment was continued in the other three patients without recurrence of paraesthesia. One patient complained of asthenia and myalgia, and two patients presented grade 2 alopecia. No haematological intolerance was observed, and thus no infection related to myelosuppression. The outcome of the patients after treatment was recorded and is shown in Table 1 and Figure 1. The median follow-up was 59 months. Progression was reported in five of the 10 patients, with a median time to progression of 14 months. However, two of these five patients were controlled with only local treatment. Three patients required further treatment by chemotherapy. Paclitaxel was reintroduced in two of them, with a favourable outcome: one did not require any other drug treatment, whereas the disease was controlled for 3 years in the other, who subsequently required other treatments. Finally, only two patients underwent other chemotherapy treatments: the patient who had received only one paclitaxel