Use of Paclitaxel to Successfully Treat Children, Adolescents, and Young Adults with Kaposi Sarcoma in Southwestern Tanzania

Abstract

Treating Kaposi sarcoma (KS) in children, adolescents, and young adults (AYA) remains a challenge in low- and middle-income countries (LMIC) where chemotherapy options and availability are limited. We describe a retrospective cohort review of pediatric patients with KS treated with paclitaxel in Mbeya, Tanzania, between 1 March 2011 and 31 December 2019. Paclitaxel was given to patients who had KS relapse, a contraindication to bleomycin, vincristine, and doxorubicin (ABV), special circumstances in which a clinician determined that paclitaxel was preferable to ABV, or experienced treatment failure, defined as persistent KS symptoms at the completion of treatment. All patients also received multidisciplinary palliative care. Seventeen patients aged 5.1–21.3 years received paclitaxel, of whom 47.1% (8/17) had treatment failure, 29.4% (5/17) received paclitaxel as initial treatment, and 23.5% (4/17) had relapsed. All HIV positive patients (16/17) were given anti-retroviral therapy (ART) and 87.5% (14/16) achieved viral load <1000 cp/mL. At censure, 82.3% (14/17) of patients were alive—71.4% (10/14) achieved complete clinical remission and 28.6% (4/14) achieved a partial response. The median follow up was 37.3 months (range 8.0–83.5, IQR 19.7–41.6), and no patients were lost to follow up. In this cohort, high rates of long-term survival and favorable outcomes were possible with paclitaxel treatment.

Divergent clinical presentations and outcomes among children and adolescents with Kaposi sarcoma in Malawi and Tanzania

“…Despite the severity of their KS and HIV disease, 51% (26/51) survived. After observing high mortality rates in patients with stage 4 disease who were treated with BV chemotherapy in our previous study in Lilongwe (2-year OS of 11.8%) [15], we treated patients with stage 4 disease at both sites with up-front intensified chemotherapy (ABV) starting in 2012, and paclitaxel was used as salvage after failure of ABV and led to encouraging outcomes with minimal toxicity in Mbeya, Tanzania [27]. Despite the difficulty of treating paediatric patients with KS visceral disease in LMICs [16,36], in this cohort, 60% (6/10) of patients with GI involvement and 42% (10/24) of patients with pulmonary KS survived.…”

“…Paclitaxel has been shown to be well-tolerated and superior to BV in a large, multicentre prospective clinical trial in adult patients with moderate to severe KS treated in LMIC settings [37]. Positive outcomes have also been reported among small paediatric cohorts [17,27,36]. Future studies may consider evaluating paclitaxel as firstline treatment for all patients with stage 2 disease if available and not cost prohibitive-or at least as an option for treatment intensification for those who do not experience CR with BV.…”

“…For patients with stage 4 disease, first-line chemotherapy was ABV, and the second-line regimen was paclitaxel. Chemotherapy dosing and toxicity monitoring have been described in detail [12,13,27]. The approach to the treatment of children without HIV with endemic KS was the same as the approach to those with HIV-related disease, apart from the provision of ART [21].…”

Circulating Biomarkers for Monitoring Chemotherapy-Induced Cardiotoxicity in Children

“…Paclitaxel is highly effective in the treatment of recurrent childhood brain tumors and is becoming a prospective management option for pediatric tumors [ 42 ]. Another study demonstrated the effectiveness of paclitaxel treatment on children affected by Kaposi sarcoma [ 43 ]. Perez-Somarriba and colleagues observed a strong response with normalization of tumor markers in three patients showing relapsed intracranial NGGCT, after treatment with gemcitabine, paclitaxel, and oxaliplatin [ 44 ].…”

Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease

“…Currently, there are no universal treatment guidelines for pediatric KS. Treatment recommendations are extrapolated based on adult KS or small retrospective studies ( 19 – 22 ). Our limited knowledge about the molecular pathobiology of pediatric KS (HIV + and HIV) constitutes a gap in our knowledge that this study aims to close.…”