Paclitaxel for relapsed or recurrent HIV-associated pediatric Kaposi's sarcoma

In sub-Saharan Africa, Kaposi's sarcoma remains a common pediatric HIV-related malignancy with primary treatment consisting of antiretroviral therapy (ART) in addition to chemotherapy with differing combinations of adriamycin, bleomycin, and vincristine (ABV) [1–3]. Due to resource limitations, salvage therapy is lacking, and patients who relapse or are refractory to therapy often have no further treatment options. Paclitaxel has been noted as an effective salvage agent in adult HIV patients. Here, we present the first report on two pediatric patients. The first patient, a 12-year-old HIV-positive male, presented to Princess Marina Hospital, the country-wide referral hospital in Gaborone, Botswana, with severe wasting, having recently started both tuberculosis (TB) therapy 2 months prior and ART 2 weeks prior. His ART therapy consisted of stavudine (d4T), lamivudine (3TC), and efavirenz (EFV). Since ART initiation, he developed lesions consistent with Kaposi's sarcoma on his left thumb and bilateral feet. He additionally presented with increased work of breathing and was found to have a large pericardial effusion. With the worsening symptoms after starting ART, both TB and Kaposi's sarcoma-associated immune reconstitution inflammatory syndrome (IRIS) were diagnostic considerations. Pericardial fluid was sent for acid-fast bacilli and cytology, both of which were negative. Due to clinical suspicion of Kaposi's sarcoma-IRIS based on the skin lesions and reports of isolated pericardial effusion as a symptom of Kaposi's sarcoma, we began therapy with bleomycin and vincristine (BV) omitting doxorubicin due to concomitant cytopenias thought secondary to bone marrow involvement or suppression from Kaposi's sarcoma [4,5]. Repeat echocardiogram after one cycle of BV showed significant improvement in the pericardial effusion, and after two additional weekly BV cycles, the patient's cytopenias resolved. He was then switched to every 3-week ABV therapy. He unfortunately proved refractory with development of significant right-sided lung involvement which worsened over two cycles of ABV. He also developed peripheral neuropathy, likely due to the combination of vincristine and d4T, so d4T was switched to abacavir (ABC). With disease progression, he was changed to paclitaxel for salvage, receiving 150 mg/m2 over 3 h with oral dexamethasone premedication 12 and 6 h prior to infusion. After one cycle, he showed dramatic improvement in his lung involvement (Fig. 1) and had no significant toxicity to therapy. Sadly, after the second paclitaxel cycle, he again showed signs of progression and passed away from respiratory symptoms.Fig. 1: Improvement in Kaposi's sarcoma pulmonary involvement after one cycle of paclitaxel.The second patient, an HIV-positive 8-year-old male on ART, presented with new respiratory symptoms and an oxygen requirement after twice previously being treated for Kaposi's sarcoma with six cycles of ABV. His ART regimen consisted of zidovidine (AZT), 3TC, and EFV. The first ABV treatment course 2 years prior was given for isolated Kaposi's sarcoma skin involvement, whereas the second course occurred a year later with pulmonary relapse. Due to this second pulmonary relapse, he was started on paclitaxel salvage therapy at a dose of 150 mg/m2 every 3 weeks, again as a 3-h infusion with oral dexamethasone premedication. After the first cycle, he showed clinical improvement with resolution of his oxygen requirement, although without significant change in his chest radiograph. He continued on every 3-week paclitaxel and achieved disease stabilization with no noted therapeutic toxicity. Although he did not have any significant myelosuppression, he was prophylactically switched from AZT to ABC. With continued disease stability, he was adjusted to every 4-week paclitaxel therapy for familial convenience and has remained stable for 12 months to date. Paclitaxel has shown both in-vitro and in-vivo evidence of activity against Kaposi's sarcoma due to inhibition of Bcl-2 antiapoptotic effects in addition to effects on microtubule depolymerization and angiogenesis [6,7]. Adult studies have shown benefit in HIV-associated Kaposi's sarcoma utilizing different treatment schedules, doses of 100–175 mg/m2 every 2–3 weeks, with neutropenia being the most common toxicity [8–12]. Vaz et al.[13] recently reported on 28 Mozambican children given paclitaxel as first-line therapy after ART initiation at a dose of 75 mg/m2 at 4-week intervals for six cycles. No grade III/IV myelosuppression was seen in our two patients. Two reports in adults have shown severe paclitaxel toxicity due to deceased metabolism with concurrent use of protease inhibitors [14,15]. Larger studies have failed to show any significant interaction [11,16]. Additionally, potential interaction between AZT and chemotherapy must be considered. Our cases highlight the safety and efficacy of paclitaxel in pediatric HIV-associated Kaposi's sarcoma that has relapsed or is refractory to standard therapy. As African countries move towards further therapies and the addition of salvage regimens, paclitaxel should be acknowledged as a plausible and reasonably inexpensive agent in pediatric patients. Acknowledgements Conflicts of interest There are no conflicts of interest.