Phase II trial of doxil for patients with metastatic melanoma refractory to frontline therapy.

Ellerhorst, Julie A.; Bedikian, A. Y.; Ring, Sigrid; Buzaid, Antônio C.; Eton, Omar; Legha, S S

doi:10.3892/or.6.5.1097

Cited by 20 publications

(19 citation statements)

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“…However, the response rate in this cohort of pre-treated melanoma patients remained well below 10%. This observation is in accordance with 2 recent publications, who used 50 mg/m 2 on a 3-week basis with a response rate of 6% (2 PR) in 32 patients [18] and 50 mg/m 2 in a 4-week interval in 14 patients without any clinical response [19]. However, it is of interest to note that 7/30 patients of our study survived >300 and 5/30 patients >400 days.…”

Section: Discussionsupporting

confidence: 74%

Clinical Phase II Study of Pegylated Liposomal Doxorubicin as Second-Line Treatment in Disseminated Melanoma

et al. 2004

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Background: Stage IV melanoma has a poor prognosis with a median survival of 3-11 months from diagnosis of distant metastases. Response rates in first-line regimens range around 15-20%. Non-responders have a median survival around 6 months. Currently, no second-line treatment in advanced melanoma has been established. Patients and Methods: In a clinical phase II study we evaluated the efficacy of liposomal doxorubicin (Caelyx?) in 30 patients (17 m, 13 f) with progressing metastatic melanoma who had failed a previous chemotherapy. Liposomal doxorubicin was given in an outpatient setting at a dose of 50 mg/m2 i.v. on d1, d22, d43 and d64, subsequently at 40 mg/m2 at d85 before first staging and in 4-week intervals thereafter. Treatment was very well tolerated with 100 cycles given in total. Response rate, survival time, time-to-progression and toxicity were assessed. Results: Erythrodysesthesia was the most severe toxicity in 6% at CTC grade 3. Liposomal doxorubicin was of limited clinical efficacy with 21 patients progressing within the first 12 weeks. However, 7 patients were treated 3-9 months and were stable for >90 days, achieving 5 SD, 1 PR and 1 CR. Median survival after initiation of second-line treatment was 214 days (95% CI: 151-304 days) with 7 patients surviving >300 and 5 patients >400 days. Conclusions: Liposomal doxorubin as monotherapy is well tolerated but of limited clinical efficacy. Whether the survival benefit of a significant proportion of patients (20%) holds true in larger cohorts and whether the efficacy of liposomal doxorubicin can be improved by combinations without compromising the low toxicity profile needs further studies.

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Section: Discussionsupporting

confidence: 74%

Clinical Phase II Study of Pegylated Liposomal Doxorubicin as Second-Line Treatment in Disseminated Melanoma

et al. 2004

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“…Liposomal drug delivery systems with doxorubicin have been extensively investigated in relapsed ovarian cancer (Muggia et al, 1997), breast cancer (Ranson et al, 1997) and others (Law et al, 1994;Schwartz and Caspar, 1995;Ellerhorst et al, 1999;Harrington et al, 2001;Judson et al, 2001). A number of trials have been performed with polymer -doxorubicin conjugate where there is covalent linkage of polymer to doxorubicin.…”

Section: Discussionmentioning

confidence: 99%

Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer

et al. 2004

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SP1049C is a novel anticancer agent containing doxorubicin and two nonionic pluronic block copolymers. In preclinical studies, SP1049C demonstrated increased efficacy compared to doxorubicin. The objectives of this first phase I study were to determine the toxicity profile, dose-limiting toxicity, maximum tolerated dose and pharmacokinetic profile of SP1049C, and to document any antitumour activity. The starting dose was 5 mg m À2 (doxorubicin content) as an intravenous infusion once every 3 weeks for up to six cycles. A total of 26 patients received 78 courses at seven dose levels. The dose-limiting toxicity was myelosuppression and DLT was reached at 90 mg m À2 . The maximum tolerated dose was 70 mg m À2 and is recommended for future trials. The pharmacokinetic profile of SP1049C showed a slower clearance than has been reported for conventional doxorubicin. Evidence of antitumour activity was seen in some patients with advanced resistant solid tumours. Phase II trials with this agent are now warranted to further define its antitumour activity and safety profile.

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“…Pegylated liposomal doxorubicin (PDOX) has been demonstrated to be active against Kaposi's sarcoma and ovarian, breast, and head and neck carcinomas [17][18][19][20]. On the other hand, no significant activity has been found against malignant mesothelioma [21], metastatic melanoma [22], hepatocellular carcinoma [23], and small-cell lung cancer [24]. In clinical trials, PDOX has been reported to induce less cardiac toxicity and myelosuppression than free doxorubicin [20,[25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Pegylated Liposomal Doxorubicin with Vinorelbine in Metastatic Breast Carcinoma

Gebbia

Mauceri²,

Fallica³

et al. 2002

Oncology

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A multicenter phase I-II trial was carried out with the aim of identifying the dose-limiting toxicity and the maximum tolerated dose of vinorelbine (VNR) in combination with pegylated liposomal doxorubicin at a dose of 20 mg/m² every 15 days in patients with metastatic breast carcinoma. In the phase I part of the trial, VNR was given at a dose of 20 mg/m² every 15 days to a group of 3 patients. In absence of unacceptable toxicity, VNR was escalated to 25, 30, and 35 mg/m² for subsequent groups of 3 patients, until the dose-limiting toxicity was reached. No case of palmar-plantar erythrodysesthesia was recorded in these patients. Grade 4 neutropenia, grade 3 thrombocytopenia, and grade 3 mucositis were the dose-limiting toxicities recorded in patients treated with VNR 35 mg/m². These side effects caused a substantial decrease in programmed dose intensity. Therefore 30 mg/m² was considered the maximum tolerated dose of VNR in combination with pegylated liposomal doxorubicin 20 mg/m², both given every 15 days. These dosages were employed for the treatment of further 18 patients included in phase II of the study. The overall response rate, calculated according to an intention to treat analysis, was 63% (95% CI: 44–80%), with 2 patients achieving a complete response. The median time to progression was 7.0 months or more (range 2–14 months). Median duration of objective responses was 8.4 months or more. The duration of the 2 complete responses was 9 and 14 months, respectively. Median duration of survival was 16.0 months or more (range from 4.0 to ≧24.0). Toxicity was generally mild and easily manageable. Neutropenia and mucositis were the most frequently recorded side effects. A case of palmar-plantar erythrodysesthesia was recorded in phase II of the study. In conclusion, the maximum tolerated dose of VNR in association with pegylated liposomal doxorubicin is 30 mg/m² on a bimonthly schedule. Moreover, the combination of VNR and pegylated liposomal doxorubicin is active against metastatic breast carcinoma and is associated with a good toxicity profile. Further studies with this combination regimen are warranted.

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Phase II trial of doxil for patients with metastatic melanoma refractory to frontline therapy.

Cited by 20 publications

References 0 publications

Clinical Phase II Study of Pegylated Liposomal Doxorubicin as Second-Line Treatment in Disseminated Melanoma

Clinical Phase II Study of Pegylated Liposomal Doxorubicin as Second-Line Treatment in Disseminated Melanoma

Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer

Pegylated Liposomal Doxorubicin with Vinorelbine in Metastatic Breast Carcinoma

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