Therapeutic Perspectives in the Systemic Treatment of Kaposi’s Sarcoma

Abstract

In patients with Kaposi’s sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.

Weekly paclitaxel treatment in the first-line therapy of classic Kaposi sarcoma: A real-life study

“…The main objectives in the treatment of CKS is not only to prolong survival and control of the disease but also to increase the quality of life of patients by improving complications, such as tumor-related edema-pain-ulceration-bleeding, functional deterioration, and lymphedema [ 7 , 8 , 11 ]…”

“…[5,8] Systemic treatment is often not required in the treatment of this chronic neoplasm, which rarely causes mortality. [7,8] Although there is no clear accepted approach on when to start systemic therapy, the general approach is during symptomatic visceral or lymph node involvement, development of diffuse symptomatic lesions on multiple body parts (not suitable for local treatments modality), or diffuse nodular disease of a large part of an extremity or widespread involvement [7,8,11] The main objectives in the treatment of CKS is not only to prolong survival and control of the disease but also to increase the quality of life of patients by improving complications, such as tumor-related edema-pain-ulceration-bleeding, functional deterioration, and lymphedema [7,8,11] Paclitaxel is an antimicrotubule agent inhibiting the anti-apoptotic effect of bcl-2, a well-known proto-oncogene that is highly expressed in KS. [21] Data on the use of paclitaxel in CKS were obtained from several retrospective studies in CKS treatment and experience in the treatment of HIV-associated KS.…”

“…[7,8,11] In advanced cases, pegylated liposomal doxorubicin (Lip-D) and paclitaxel are the most preferred agents as first-and second line therapy, regardless of KS subtype. [7,8,11] Other chemotherapeutic agents for KS treatment include oral etoposide, vinblastine, bleomycin, vinorelbine, and gemcitabine. [7,8] Data on the efficacy of paclitaxel in CKS were obtained from retrospective studies [12][13][14][15] and have been inferred from data supporting the use of paclitaxel in AIDS-related KS.…”

“…Although CKS often does not require systemic therapy, in advance cases chemoterapy can be administered in progressively symptomatic patients to reduce the number and size of lesions and alleviate disease-related severe symptoms reducing quality of life such as bleeding, pain, lymphedema, and functional disorders. [ 7 , 8 , 11 ] In advanced cases, pegylated liposomal doxorubicin (Lip-D) and paclitaxel are the most preferred agents as first- and second line therapy, regardless of KS subtype. [ 7 , 8 , 11 ] Other chemotherapeutic agents for KS treatment include oral etoposide, vinblastine, bleomycin, vinorelbine, and gemcitabine.…”

“…[12][13][14][15] In the literature review, studies showing effectiveness and safety of weekly paclitaxel therapy as a first-line chemotherapy for CKS were very few and conducted in a very small sample size. [11][12][13][14] In this real-life study we purposed to investigate the effectiveness and safety of paclitaxel therapy in the first-line treatment of CKS in a large sample size with 20 years of experience in our tertiary cancer center.…”