A Phase II Nonrandomised Open-Label Study of Liposomal Daunorubicin (DaunoXome) in Advanced Soft Tissue Sarcoma

McTiernan, Anne; Whelan, Jeremy; Leahy, Michael; Woll, Penella J.; Judson, Ian

doi:https://doi.org/10.1155/SRCM/2006/41080

Sarcoma

On this page

Abstract References Copyright Related Articles

Clinical Study | Open Access

Volume 2006 | Article ID 041080 | https://doi.org/10.1155/SRCM/2006/41080

A Phase II Nonrandomised Open-Label Study of Liposomal Daunorubicin (DaunoXome) in Advanced Soft Tissue Sarcoma

Anne McTiernan,¹Jeremy Whelan,¹Michael Leahy,²Penella J. Woll,^3,4and Ian Judson⁵

Received26 Apr 2005

Revised30 Dec 2005

Accepted14 Feb 2006

Published10 May 2006

Abstract

Thirty four patients with advanced soft tissue sarcoma not previously treated with an anthracycline were treated with DaunoXome 100mg/m2 every 3 weeks. Thirty-three patients were evaluable for toxicity. Grade 3-4 neutropenia was seen in 20 patients (60.6%), complicated by febrile neutropenia in 2 (6.1%). Other grade 3 toxicities were rare. Among 32 patients assessable for response, one patient had a partial response, giving a response rate of 3.13% (95% confidence interval, 0.08–16.22%). Seven patients (21.9%) had stable disease, and 24 patients (75.0%) had disease progression. The median time to progression for all patients was 42 days (95% CI, 39–49) and the progression-free rate at 3 months was 12.5%. In conclusion, DaunoXome at this dose and schedule is well tolerated in patients with advanced soft tissue sarcoma, but is not associated with significant activity. Further studies at this dose and schedule cannot be recommended in this disease.

References

M Van Glabbeke, A T Van Oosterom, J W Oosterhuis et al., “Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline- containing first-line regimens - a European organization for research and treatment of cancer soft tissue and bone sarcoma group study,” Journal of Clinical Oncology, vol. 17, no. 1, pp. 150–157, 1999.
View at: Google Scholar
V H Bramwell, D Anderson, and M L Charette, “Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft tissue sarcoma,” Cochrane Database of Systematic Reviews, vol. 3, p. CD003293, 2003.
View at: Google Scholar
O S Nielsen, P Dombernowsky, H Mouridsen et al., “High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas. A study of the EORTC soft tissue and bone sarcoma group,” British Journal of Cancer, vol. 78, no. 12, pp. 1634–1639, 1998.
View at: Google Scholar
I Judson, J A Radford, M Harris et al., “Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL®/CAELYX®) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group,” European Journal of Cancer, vol. 37, no. 7, pp. 870–877, 2001.
View at: Google Scholar
A Santoro, T Tursz, H Mouridsen et al., “Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first- line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group,” Journal of Clinical Oncology, vol. 13, no. 7, pp. 1537–1545, 1995.
View at: Google Scholar
E A Forssen, D M Coulter, and R T Proffitt, “Selective in vivo localization of daunorubicin small unilamellar vesicles in solid tumors,” Cancer Research, vol. 52, no. 12, pp. 3255–3261, 1992.
View at: Google Scholar
P S Gill, B M Espina, F Muggia et al., “Phase I/II clinical and pharmacokinetic evaluation of liposomal daunorubicin,” Journal of Clinical Oncology, vol. 13, no. 4, pp. 996–1003, 1995.
View at: Google Scholar
P Guaglianone, K Chan, E DelaFlor-Weiss et al., “Phase I and pharmacologic study of liposomal daunorubicin (DaunoXome),” Investigational New Drugs, vol. 12, no. 2, pp. 103–110, 1994.
View at: Google Scholar
P Cohen, P S Gill, J Wernz, D T Scadden, G M Mukwaya, and R Sandhaus, “Absence of cardiac toxicity in patients who received 3 600 mg/m2 of liposomal encapsulated daunorubicin (DaunoXome),” Proceedings of the American Society of Clinical Oncology, vol. 16, p. 761, 1997, (abstract).
View at: Google Scholar
K J O'Byrne, A L Thomas, R A Sharma et al., “A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer,” British Journal of Cancer, vol. 87, no. 1, pp. 15–20, 2002.
View at: Google Scholar
R JJ Lippens, “Liposomal daunorubicin (DaunoXome) in children with recurrent or progressive brain tumors,” Pediatric Hematology and Oncology, vol. 16, no. 2, pp. 131–139, 1999.
View at: Google Scholar
A Tulpule, M U Rarick, J Kolitz et al., “Liposomal daunorubicin in the treatment of relapsed or refractory non-Hodgkin's lymphoma,” Annals of Oncology, vol. 12, no. 4, pp. 457–462, 2001.
View at: Google Scholar
P S Gill, J Wernz, D T Scadden et al., “Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma,” Journal of Clinical Oncology, vol. 14, no. 8, pp. 2353–2364, 1996.
View at: Google Scholar
P-M Girard, O Bouchaud, A Goetschel et al., “Phase II study of liposomal encapsulated daunorubicin in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma,” AIDS, vol. 10, no. 7, pp. 753–757, 1996.
View at: Google Scholar
Cancer Therapy Evaluation Program. Common Toxicity Criteria, Version 2.0: DCTD, NCI, NIH, DHHS, March 1998.
World Health Organisation. Handbook for Reporting Results of Cancer Treatment, World Health Organisation Offset Publication, no. 48, World Health Organisation, Geneva, Switzerland, 1979.
E A Gehan, “The determination of the number of patients required in a preliminary and follow up trial of a used chemotherapy agent,” Journal of Chronic Diseases, vol. 13, pp. 346–353, 1961.
View at: Google Scholar
D D Von Hoff, “Use of daunorubicin in patients with solid tumors,” Seminars in Oncology, vol. 11, no. 4 suppl. 3, pp. 23–27, 1984.
View at: Google Scholar
P M Deckert, J M Siehl, E Thiel et al., “Phase II study of liposomal daunorubicin and ifosfamide (IDx) as first line chemotherapy in soft tissue sarcoma,” Proceedings of the American Society of Clinical Oncology, vol. 23, p. 816(A9011), 2004.
View at: Google Scholar
M Van Glabbeke, J Verweij, I Judson, and O S Nielsen, “Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas,” European Journal of Cancer, vol. 38, no. 4, pp. 543–549, 2002.
View at: Google Scholar

Copyright

Copyright © 2006 Anne McTiernan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation Order printed copies

Views

345

Downloads

765

Citations