Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group.

Stewart, Simon; Jablonowski, H; Goebel, Franc D.; Arastéh, Keikawus; Spittle, Margaret F.; Rios, Adan; Aboulafia, David M.; Galleshaw, J.; Dezube, Bruce J.

doi:10.1200/jco.1998.16.2.683

Cited by 304 publications

(151 citation statements)

References 15 publications

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“…Mucositis was also rare and mild. No infusionrelated reactions, which are sometimes seen in cases of liposomal drug administration (Uziely et al, 1995;Muggia et al, 1996;Stewart et al, 1998;Gordon et al, 2001), occurred in this trial. Ultimately, this phase I study showed that the recommended dosage of NK911 (50 mg m À2 ) using a 3-week schedule was similar to the recommended dosage of free DXR (40 -60 mg m À2 ).…”

Section: Discussionmentioning

confidence: 66%

“…Doxil is comprised of doxorubicin (DXR) encapsulated in STEALTHt liposomes, which are composed of a phospholipid bilayer with surface-bound methoxypolyethyleneglycol. Doxil recently received the US Food and Drug Administration's (FDA) approval for use in the treatment of Kaposi sarcoma or ovarian cancer after the clinical benefits of this drug were clearly shown in recent clinical trials (Muggia et al, 1996;Stewart et al, 1998;Gordon et al, 2001).…”

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confidence: 99%

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Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

Matsumura

Hamaguchi²,

Umemura³

et al. 2004

Br J Cancer

569

283

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NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min À1 . The starting dose was 6 mg DXR equivalent m À2 , and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m À2 . Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m À2 (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C 5 min and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m À2 every 3 weeks.

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Section: Discussionmentioning

confidence: 66%

mentioning

confidence: 99%

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

Matsumura

Hamaguchi²,

Umemura³

et al. 2004

Br J Cancer

569

283

View full text Add to dashboard Cite

show abstract

“…Entre los múltiples agentes utilizados la adriamicina liposomal y el paclitaxel 15,16 son considerados los agentes más activos. En dos estudios fase III la adriamicina liposomal demostró un mayor índice de respuestas y un mejor perfil de toxicidad que esquemas de poliquimioterapia 17,18 . No se debe olvidar realizar profilaxis frente a Pneumocystis carinii y puede ser necesario instaurar tratamiento con G-CSF.…”

Section: Discussionunclassified

Infección VIH y sarcoma de Kaposi: a propósito de un caso

Baz

Delgado

2005

Oncología (Barc.)

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Resumen• Propósito: El sarcoma de Kaposi es el cáncer más frecuente entre los pacientes con infección VIH aunque el riesgo ha disminuido con el tratamiento antirretroviral. Realizamos una revisión bibliográfica de esta enfermedad.• Material y métodos: Se presenta el caso de un varón de 49 años VIH + diagnosticado de sarcoma de Kaposi con afectación visceral y tratado con adriamicina liposomal.• Conclusiones: Si la enfermedad es sintomática, rápidamente progresiva o existe afectación visceral se debe iniciar quimioterapia.

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“…Preclinical studies have shown that cytotoxic drugs entrapped in pegylated liposomes are active against a range of tumours (Harrington et al, 2000a). Clinical studies of pegylated liposomal doxorubicin have confirmed its activity against AIDS-related Kaposi's sarcoma (Northfelt et al, 1998;Stewart et al, 1998) and breast and ovarian cancers (Muggia et al, 1997;Ranson et al, 1997) with considerable attenuation of the adverse effects of the unencapsulated drug. Furthermore, preclinical and Phase I/II trials of pegylated liposomal doxorubicin and radiotherapy (RT) have supported the feasibility of this approach in head and neck and lung cancers (Koukourakis et al, 1999;Harrington et al, 2000b, c;Harrington et al, 2001a).…”

mentioning

confidence: 96%

Targeted radiosensitisation by pegylated liposome-encapsulated 3′, 5′-O-dipalmitoyl 5-iodo-2′-deoxyuridine in a head and neck cancer xenograft model

et al. 2004

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5-Iodo-20 -deoxyuridine (IUdR) is an effective radiosensitiser but its clinical development has been limited by toxicity. Prolonged intravenous infusions of IUdR are necessary for optimal tumour uptake but cause dose-limiting myelosuppression. The lack of selective tumour uptake can lead to radiosensitisation of adjacent normal tissues and enhanced local radiation toxicity. Liposomal IUdR delivery offers selective targeting of tumour tissues and avoidance of local and systemic toxicity. In these studies, we report the development of a pegylated liposome containing a lipophilic IUdR derivative (3 0 , 5 0 -O-dipalmitoyl-5-iodo-2 0 -deoxyuridine) for use in a head and neck cancer xenograft model. Initial studies confirmed the ability of IUdR to sensitise two head and neck cancer cell lines to single fractions of radiotherapy (SFRT) and this effect was seen to correlate with the thymidine replacement index in KB cells. In vivo delivery of single doses of either unencapsulated IUdR or pegylated liposomal IUdR (PLIUdR) to nude mice bearing KB xenograft tumours did not enhance the effect of SFRT delivered 16 h later. When PLIUdR was delivered by a protracted administration schedule to a dose of 48 mg kg À1 over 7 days, it enhanced the effect of both 4.5 Gy SFRT and fractionated radiotherapy. PLIUdR was at least as effective as unencapsulated IUdR delivered by multiple intravenous injections or continuous subcutaneous infusion. Immunohistochemistry with a specific anti-IUdR monoclonal antibody confirmed greater levels of tumour staining in tumours from animals treated with PLIUdR compared with those treated with unencapsulated IUdR.

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Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group.

Abstract: Pegylated liposomal doxorubicin is an effective treatment for HIV-related Kaposi's sarcoma with a higher response rate than the BV combination. It is well tolerated but more myelosuppressive.

Cited by 304 publications

References 15 publications

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

Infección VIH y sarcoma de Kaposi: a propósito de un caso

Targeted radiosensitisation by pegylated liposome-encapsulated 3′, 5′-O-dipalmitoyl 5-iodo-2′-deoxyuridine in a head and neck cancer xenograft model

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