Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies.

Uziely, Beatrice; Jeffers, Susan; Isacson, Rut; Kutsch, Kimberlea; Wei-Tsao, Denise; Yehoshua, Zohar; Libson, Eugene; Fm, Muggia; Gabizón, Alberto

doi:10.1200/jco.1995.13.7.1777

Cited by 439 publications

(224 citation statements)

References 22 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%

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

Matsumura

Hamaguchi²,

Umemura³

et al. 2004

Br J Cancer

578

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%

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

Matsumura

Hamaguchi²,

Umemura³

et al. 2004

Br J Cancer

578

283

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“…Phase I trials of SL-DOX have indicated that SL-DOX has activity in breast, ovarian, head and neck, prostatic, renal cell and non-smallcell lung carcinomas (Uziely et al, 1995).…”

Section: Results Patientsmentioning

confidence: 99%

Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi's sarcoma

Goebel¹,

Goldstein²,

Goos³

et al. 1996

Br J Cancer

100

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Summary The utility of current chemotherapeutic regimens in the treatment of AIDS-related Kaposi 44 (18.5%) had stable disease and two (0.8%) had disease progression. SL-DOX was well tolerated: ten patients discontinued therapy because of adverse events, in four cases because of neutropenia. Grade 3 or 4 neutropenia occurred after 281 of 2023 cycles (13.9%) but involved 137 of 240 patients (57.1%) for whom data were available. SL-DOX has substantial activity in AIDS-KS. Best response is typically seen after fewer than three cycles of chemotherapy and in some cases may be prolonged. The most important adverse event is neutropenia, which occurs after a minority of cycles but which may occur in over half of all patients.

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“…Dose-limiting toxicities of PLD include reversible neutropaenia, stomatitis and plantar-palmar erythrodysaesthesia. Alopecia and emesis are infrequent (Uziely et al, 1995). A phase I study in 33 patients with advanced HCC determined neutropaenia as the doselimiting toxicity at 60 mg m À2 and recommended 50 mg m À2 every 28 days as the phase II dosing regimen (Schering Plough -data on file).…”

mentioning

confidence: 99%

Treatment of inoperable hepatocellular carcinoma with pegylated liposomal doxorubicin (PLD): results of a phase II study

et al. 2005

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Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies.

Cited by 439 publications

References 22 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

Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi's sarcoma

Treatment of inoperable hepatocellular carcinoma with pegylated liposomal doxorubicin (PLD): results of a phase II study

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