Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial

Krown, Susan E.; Moser, Carlee; MacPhail, Patrick; Matining, Roy M.; Godfrey, Catherine; Caruso, Stephanie; Hosseinipour, Mina C.; Samaneka, Wadzanai; Nyirenda, Mulinda; Busakhala, Naftali; Okuku, Fred; Kosgei, Josphat; Hoagland, Brenda; Mwelase, Noluthando; Oliver, Vincent O; Burger, Henriette; Mngqibisa, Rosie; Nokta, Mostafa; Campbell, Thomas; Borok, Margaret; Moses, Agnes; Kanyama, Cecilia; Mukwekwerere, Pamela G; Gudza, Ivy; Chauwa, Felluna; Ulaya, Godwin; Kutto, Irene; Cheruiyot, Priscilla; Okello, Clement Dove; Nakaganda, Annet; Koskei, Geoffrey; Keter, Winnie; Netto, Juliana; Baião, Tamiris; Govender, Iveshni; O'Connell-Maritz, Jessica; Cain, Kevin P.; Okanda, John; Cornelissen, Lynne; Schalkwyk, Marije Van; Sikhosana, Rejoice; Ngcobo, Minenhle; Lee, Jeannette; Harrison, Taylor; Wachsman, William; Shin, Katherine; Evans, Scott; Rothenberg, Jennifer; Hosey, Lara; McCarthy, Seán; Martı́nez-Maza, Otoniel; Rinaldo, Charles R.; Dittmer, Dirk P.; Fletcher, Courtney; Rudek, Michelle A.; Asmelash, Aida; Hughes, Valery; Schouten, Jeffrey T.; Shugarts, David; Kujinga, Tapiwanashe; Zadzilka, Amanda; Kerui, Fredrick; Robertson, Debora; Rooney, James F.; Sewal, Krishna; Gottshall, Brian

doi:10.1016/s0140-6736(19)33222-2

Cited by 60 publications

(81 citation statements)

References 29 publications

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“…The traditional ABV regimen is not ideal, because of substandard outcomes and an unfavorable side effect profile, so finding less toxic alternatives is urgent. Indeed, paclitaxel was recently shown to be superior to both a combination of bleomycin and vincristine and also to oral etoposide in a multi-centric trial in southern Africa, though we note that paclitaxel toxicities were largely the same compared to the vincristine/bleomycin group [26]. We are unable to compare our observational results with PLD with those from the paclitaxel trial, but future research in Africa should include head-to-head testing of PLD and paclitaxel.…”

Section: Improving Chemotherapy Regimens In Sub-saharan Africamentioning

confidence: 68%

“…The hematologic toxicities seen were generally of moderate severity, and not unexpected. And although some patients needed transfusions, the side effects of PLD were less limiting and less toxic to the patients than with the previous ABV regimen, and also those described with the use of paclitaxel monotherapy [17,26]. While data on the incidence of hand-foot syndrome in Sub-Saharan Africa are scarce, it is possible that the relatively lower doses and the three-week interval between doses may explain its rarity in this cohort.…”

Section: Safety Of Pldmentioning

confidence: 73%

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Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin

Coldiron¹,

Zamudio²,

Manuel

et al. 2021

Infect Agents Cancer

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Background Kaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique. Methods We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment. Results At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2–6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD. Discussion PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.

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Section: Improving Chemotherapy Regimens In Sub-saharan Africamentioning

confidence: 68%

Section: Safety Of Pldmentioning

confidence: 73%

Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin

Coldiron¹,

Zamudio²,

Manuel

et al. 2021

Infect Agents Cancer

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“…Multiple chemotherapy options are recommended factoring in the cost-effectiveness and the superior efficiency of the drugs including pegylated liposomal doxorubicin and paclitaxel. [ 41 ] While paclitaxel has been found to be most effective, bleomycin has also shown promising results. [ 41 ] Lenalidomide, interferon α, and immune checkpoint inhibitors (nivolumab, pembrolizumab) are being studied in clinical trials.…”

Section: Ocular Lesions Due To Opportunistic Infectionsmentioning

confidence: 99%

“…[ 41 ] While paclitaxel has been found to be most effective, bleomycin has also shown promising results. [ 41 ] Lenalidomide, interferon α, and immune checkpoint inhibitors (nivolumab, pembrolizumab) are being studied in clinical trials. [ 41 ] KSHV inflammatory cytokine syndrome (KICS), a cytokine mediated response (IL6/IL10), due to HHV-8 reactivation, presenting with multiple severe inflammatory symptoms has recently been reported.…”

Section: Ocular Lesions Due To Opportunistic Infectionsmentioning

confidence: 99%

Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy – An update

Sridharan

Nair

Curi

et al. 2020

Indian J Ophthalmol

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Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.

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“…The second collaborative AMC/ACTG study (ClinicalTrials.gov identifier: NCT01435018 ) was a randomized controlled trial to investigate optimal chemotherapy regimens combined with effective ART for people with advanced AIDS-associated KS. 21 This study randomly assigned 334 PLWH (96% from SSA) with advanced-stage AIDS-associated KS to receive ART concurrently with open-label chemotherapy—either bleomycin combined with vincristine or oral etoposide (the investigational arms), or paclitaxel (the active control). The study showed that when combined with an effective ART regimen, paclitaxel was superior to both bleomycin combined with vincristine and oral etoposide with respect to progression-free survival, overall response rate, response duration, and a composite of time to progression or death.…”

Section: Hivam Trials In Ssamentioning

confidence: 99%

Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers

Lin

Lakomy

Chiao

et al. 2020

JCO Global Oncology

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PURPOSE The aim of this study was to review the current status of clinical trials for HIV-associated malignancies in people living with HIV in sub-Saharan Africa (SSA) and efforts made by the AIDS Malignancy Consortium (AMC) to build capacity in SSA for HIV malignancy research. METHODS All malignancy-related clinical trials in 49 SSA countries on ClinicalTrials.gov were reviewed and evaluated for inclusion and exclusion criteria pertaining to HIV status. Additional studies by AMC in SSA were compiled from Web-based resources, and narrative summaries were prepared to highlight AMC capacity building and training initiatives. RESULTS Of 96 cancer trials identified in SSA, only 11 focused specifically on people living with HIV, including studies in Kaposi sarcoma, cervical dysplasia and cancer, non-Hodgkin lymphoma, and ocular surface squamous neoplasia. Recognizing the increasing cancer burden in the region, AMC expanded its clinical trial activities to SSA in 2010, with 4 trials completed to date and 6 others in progress or development, and has made ongoing investments in developing research infrastructure in the region. CONCLUSION As the HIV-associated malignancy burden in SSA evolves, research into this domain has been limited. AMC, the only global HIV malignancy-focused research consortium, not only conducts vital HIV-associated malignancies research in SSA, but also develops pathology, personnel, and community-based infrastructure to meet these challenges in SSA. Nonetheless, there is an ongoing need to build on these efforts to improve HIV-associated malignancies outcomes in SSA.

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Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial

Cited by 60 publications

References 29 publications

Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin

Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin

Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy – An update

Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers

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