This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gordon, A. N. Articles by Sharpington, T. Search for Related Content PubMed PubMed Citation Articles by Gordon, A. N. Articles by Sharpington, T. Social Bookmarking                            What's this?

Phase II Study of Liposomal Doxorubicin in Platinum- and Paclitaxel-Refractory Epithelial Ovarian Cancer

From the Physicians Reliance Network, Dallas, TX; Women’s and Infants Hospital, Providence, RI; University Hospitals, Cleveland, OH; The Sarah Cannon Cancer Center, Nashville, TN; Arizona Cancer Center, Tucson, AZ; Capital District Hematology Oncology, Latham, NY; and Alza Corporation, Palo Alto, CA.

Address reprint requests to Alan N. Gordon, MD, Texas Oncology, PA, 3535 Worth St, Suite S-200, Dallas, TX 7524; email alan.gordon @usoncology.com.

PURPOSE: Stealth liposomal doxorubicin (Alzal Corp, Palo Alto, CA) has a slower clearance rate than free doxorubicin, resulting in sustained serum levels. Liposomal encapsulation also leads to increased concentration of drug in tumor tissue. Meta-analysis of previous studies has shown that doxorubicin has activity in epithelial ovarian cancer. The current study was developed to examine the activity of Stealth liposomal doxorubicin in platinum- and paclitaxel-refractory ovarian cancer.

PATIENTS AND METHODS: Patients had epithelial ovarian cancer that either progressed on or recurred within 6 months of completion of platinum and paclitaxel chemotherapy. All patients had measurable disease. Stealth liposomal doxorubicin was administered at 50 mg/m² every 4 weeks as a 1-hour infusion.

RESULTS: Eighty-nine patients were treated and included in an intent-to-treat analysis. There were 82 patients who were platinum and paclitaxel refractory and met all study criteria. There was one complete response and 14 partial responses, for a total response rate of 16.9% (95% confidence interval [CI], 9.1% to 24.6%). For platinum- and paclitaxel-refractory patients, the response rate was 18.3% (95% CI, 9.9% to 26.7%). Median time to progression was 19.3 weeks for the entire population. Ten patients (11.2%) withdrew because of adverse events related to the drug (palmar-plantar erythrodysesthesia [PPE], n = 3; asthenia, n = 2; cardiac, n = 2; neutropenia, n = 1; stomatitis, n = 1; and edema, n = 1). There were no drug-related fatal events. There were only eight grade 4 adverse events attributable to the drug. Stomatitis, PPE, and skin lesions were managed with dose reductions and delays in most cases.

CONCLUSION: Stealth liposomal doxorubicin has activity in refractory epithelial ovarian cancer. PPE and stomatitis can usually be managed by dose adjustment. The ease of administration makes this an attractive agent.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. J. Hoskins Triple Cytotoxic Therapy for Advanced Ovarian Cancer: A Failed Application, Not a Failed Strategy J. Clin. Oncol., March 20, 2009; 27(9): 1355 - 1358. [Full Text] [PDF]

				F. Pastorino, D. Di Paolo, F. Piccardi, B. Nico, D. Ribatti, A. Daga, G. Baio, C. E. Neumaier, C. Brignole, M. Loi, et al. Enhanced Antitumor Efficacy of Clinical-Grade Vasculature-Targeted Liposomal Doxorubicin Clin. Cancer Res., November 15, 2008; 14(22): 7320 - 7329. [Abstract] [Full Text] [PDF]

				N. Katsumata, Y. Fujiwara, T. Kamura, T. Nakanishi, M. Hatae, D. Aoki, K. Tanaka, H. Tsuda, S. Kamiura, K. Takehara, et al. Phase II Clinical Trial of Pegylated Liposomal Doxorubicin (JNS002) in Japanese Patients with Mullerian Carcinoma (Epithelial Ovarian Carcinoma, Primary Carcinoma of Fallopian Tube, Peritoneal Carcinoma) Having a Therapeutic History of Platinum-based Chemotherapy: A Phase II Study of the Japanese Gynecologic Oncology Group Jpn. J. Clin. Oncol., November 1, 2008; 38(11): 777 - 785. [Abstract] [Full Text] [PDF]

				D. G. Mutch, M. Orlando, T. Goss, M. G. Teneriello, A. N. Gordon, S. D. McMeekin, Y. Wang, D. R. Scribner Jr, M. Marciniack, R. W. Naumann, et al. Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer J. Clin. Oncol., July 1, 2007; 25(19): 2811 - 2818. [Abstract] [Full Text] [PDF]

				E Andreopoulou, D Gaiotti, E Kim, A Downey, D Mirchandani, A Hamilton, A. Jacobs, J. Curtin, and F Muggia Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil(R)): Experience with long-term maintenance in responding patients with recurrent epithelial ovarian cancer Ann. Onc., April 1, 2007; 18(4): 716 - 721. [Abstract] [Full Text] [PDF]

				M. Markman New, Expanded, and Modified Use of Approved Antineoplastic Agents in Ovarian Cancer Oncologist, February 1, 2007; 12(2): 186 - 190. [Abstract] [Full Text] [PDF]

				R. L. Coleman, A. Gordon, J. Barter, S. Sun, W. Rackoff, and T. J. Herzog Early Changes in CA125 After Treatment with Pegylated Liposomal Doxorubicin or Topotecan Do Not Always Reflect Best Response in Recurrent Ovarian Cancer Patients Oncologist, January 1, 2007; 12(1): 72 - 78. [Abstract] [Full Text] [PDF]

				D. Pectasides, E. Pectasides, and T. Economopoulos Fallopian Tube Carcinoma: A Review Oncologist, September 1, 2006; 11(8): 902 - 912. [Abstract] [Full Text] [PDF]

				S. Campos, O. Hamid, M. V. Seiden, A. Oza, M. Plante, R. K. Potkul, P. F. Lenehan, E. P. Kaldjian, M. L. Varterasian, C. Jordan, et al. Multicenter, Randomized Phase II Trial of Oral CI-1033 for Previously Treated Advanced Ovarian Cancer J. Clin. Oncol., August 20, 2005; 23(24): 5597 - 5604. [Abstract] [Full Text] [PDF]

				D. Mirchandani, H. Hochster, A. Hamilton, L. Liebes, H. Yee, J. P. Curtin, S. Lee, J. Sorich, C. Dellenbaugh, and F. M. Muggia Phase I Study of Combined Pegylated Liposomal Doxorubicin with Protracted Daily Topotecan for Ovarian Cancer Clin. Cancer Res., August 15, 2005; 11(16): 5912 - 5919. [Abstract] [Full Text] [PDF]

				C. Sessa, F. De Braud, A. Perotti, J. Bauer, G. Curigliano, C. Noberasco, F. Zanaboni, L. Gianni, S. Marsoni, J. Jimeno, et al. Trabectedin for Women With Ovarian Carcinoma After Treatment With Platinum and Taxanes Fails J. Clin. Oncol., March 20, 2005; 23(9): 1867 - 1874. [Abstract] [Full Text] [PDF]

				P. G. Rose Pegylated Liposomal Doxorubicin: Optimizing the Dosing Schedule in Ovarian Cancer Oncologist, March 1, 2005; 10(3): 205 - 214. [Abstract] [Full Text] [PDF]

				D. Katsaros, M. V. Oletti, I. A. Rigault de la Longrais, A. Ferrero, A. Celano, S. Fracchioli, M. Donadio, R. Passera, L. Cattel, and C. Bumma Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma Ann. Onc., February 1, 2005; 16(2): 300 - 306. [Abstract] [Full Text] [PDF]

				T. J. Herzog Recurrent Ovarian Cancer: How Important Is It to Treat to Disease Progression? Clin. Cancer Res., November 15, 2004; 10(22): 7439 - 7449. [Abstract] [Full Text] [PDF]

				A. Iop, A. M. Manfredi, and S. Bonura Fatigue in cancer patients receiving chemotherapy: an analysis of published studies Ann. Onc., May 1, 2004; 15(5): 712 - 720. [Abstract] [Full Text] [PDF]

				R. Tambaro, S. Greggi, R. V. Iaffaioli, A. Rossi, C. Pisano, L. Manzione, E. Ferrari, M. Di Maio, F. Iodice, G. Casella, et al. An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer Ann. Onc., September 1, 2003; 14(9): 1406 - 1411. [Abstract] [Full Text] [PDF]

				A. Chanan-Khan, J. Szebeni, S. Savay, L. Liebes, N. M. Rafique, C. R. Alving, and F. M. Muggia Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil(R)): possible role in hypersensitivity reactions Ann. Onc., September 1, 2003; 14(9): 1430 - 1437. [Abstract] [Full Text] [PDF]

				G. J. R. Charrois and T. M. Allen Multiple Injections of Pegylated Liposomal Doxorubicin: Pharmacokinetics and Therapeutic Activity J. Pharmacol. Exp. Ther., September 1, 2003; 306(3): 1058 - 1067. [Abstract] [Full Text] [PDF]

				M. L. Rothenberg, P.Y. Liu, P. S. Braly, S. P. Wilczynski, E. V. Hannigan, S. Wadler, G. Stuart, C. Jiang, M. Markman, and D. S. Alberts Combined Intraperitoneal and Intravenous Chemotherapy for Women With Optimally Debulked Ovarian Cancer: Results From an Intergroup Phase II Trial J. Clin. Oncol., April 1, 2003; 21(7): 1313 - 1319. [Abstract] [Full Text] [PDF]

				D. K. Armstrong Relapsed Ovarian Cancer: Challenges and Management Strategies for a Chronic Disease Oncologist, October 1, 2002; 7(90005): 20 - 28. [Abstract] [Full Text] [PDF]

				V. H. C. Bramwell, D. Morris, D. S. Ernst, I. Hings, M. Blackstein, P. M. Venner, E. I. Ette, M. W. Harding, A. Waxman, and G. D. Demetri Safety and Efficacy of the Multidrug-Resistance Inhibitor Biricodar (VX-710) with Concurrent Doxorubicin in Patients with Anthracycline-resistant Advanced Soft Tissue Sarcoma Clin. Cancer Res., February 1, 2002; 8(2): 383 - 393. [Abstract] [Full Text] [PDF]

				O. Lyass, A. Hubert, and A. A. Gabizon Phase I Study of Doxil-Cisplatin Combination Chemotherapy in Patients with Advanced Malignancies Clin. Cancer Res., October 1, 2001; 7(10): 3040 - 3046. [Abstract] [Full Text] [PDF]

				A. N. Gordon, J. T. Fleagle, D. Guthrie, D. E. Parkin, M. E. Gore, and A. J. Lacave Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan J. Clin. Oncol., July 15, 2001; 19(14): 3312 - 3322. [Abstract] [Full Text] [PDF]

				G. Frykman, G. Williams, R. Pazdur, and A. N. Gordon Conflicting Phase II Efficacy Data for Doxil J. Clin. Oncol., January 15, 2001; 19(2): 596 - 597. [Full Text] [PDF]

				S. N. Goldberg, G. D. Girnan, A. N. Lukyanov, M. Ahmed, W. L. Monsky, G. S. Gazelle, J. C. Huertas, K. E. Stuart, T. Jacobs, V. P. Torchillin, et al. Percutaneous Tumor Ablation: Increased Necrosis with Combined Radio-frequency Ablation and Intravenous Liposomal Doxorubicin in a Rat Breast Tumor Model Radiology, March 1, 2002; 222(3): 797 - 804. [Abstract] [Full Text] [PDF]