A Pilot Study of Gemcitabine and Epirubicin Combination Chemotherapy as a Salvage Regimen for Recurrent Platinum Resistant and/or Refractory Epithelial Ovarian Cancer — Oak Academic Publishing
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A Pilot Study of Gemcitabine and Epirubicin Combination Chemotherapy as a Salvage Regimen for Recurrent Platinum Resistant and/or Refractory Epithelial Ovarian Cancer
<b>BACKGROUND AND OBJECTIVES:</b> The objective of this study was to assess the antitumor activity and toxicity profile of gemcitabine combined with epirubicin in patients with recurrent platinum refractory ovarian epithelial cancer. <b>PATIENTS AND METHODS:</b> Patients with recurrent platinum refractory ovarian cancer and with adequate hematologic, renal and hepatic function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 were enrolled. The regimen was Gemcitabine 1000 mg/m2 (day 1, 8) and Epirubicin 60 mg/m2 (day 1), the cycle was repeated at interval of 21 days. <b>RESULTS:</b> Twenty eight patients were recruited and received 156 cycles of gemcitabine-epirubicin combination chemotherapy (median 6 cycles). Overall response rate was 42.9% (95% CI equal 24.5 to 62.7) and tumor control rate was 75% (95% CI equal 55.1 to 89.3). No complete responses were observed. Median progression-free and median overall survival times were 7 and 15 months, respectively. The most common grade 3/4 hematological toxicities were neutropenia (57.1%), anemia (10.7%), and thrombocytopenia (7.1%), while the most common grade 3/4 non-hematological toxicities were mucositis (14.3%) and vomiting (3.6%). No treatment related deaths were observed. <b>CONCLUSION:</b> Gemcitabine combined with epirubicin regimen appeared to offer an acceptable clinical profile in patients with recurrent platinum-refractory epithelial ovarian cancer.
A. Jemal, R. Siegel, E. Ward, et al., “Cancer Statistics,” CA: A Cancer Journal for Clinicians, Vol. 59, No. 4, 2009, pp. 225-249. doi:10.3322/caac.20006
A. du Bois, M. Quinn, T. Thigpen, J. Vermorken, E. Vall-Lundqvist, M. Bookman, D. Bowtell, M. Brady, A. Casado, A. Cervantes, et al., “2004 Consensus Statements on the Management of Ovarian Cancer: Final Document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004),” Annals of Oncology, Vol. 16, No. 8, 2005, pp. viii7-viii12.
R. F. Ozols, B. N. Bundy, B. E. Greer, et al., “Phase III Trial of Carboplatin and Paclitaxel Compared with Cisplatin and Paclitaxel in Patients with Optimally Resected Stage III Ovarian Cancer: A Gynecologic Oncology Group Study,” Journal of Clinical Oncology, Vol. 21, No. 17, 2003, pp. 3194-3200. doi:10.1200/JCO.2003.02.153
A. Gadducci, F. Landoni, T. Maggino, et al., “Serum CA125 Assay at the Time of Relapse Has No Prognostic Relevance in Patients Undergoing Chemotherapy for Recurrent Ovarian Cancer: A Multicenter Italian Study,” International Journal of Gynecological Cancer, Vol. 7, No. 1, 1997, pp. 78-83. doi:10.1046/j.1525-1438.1997.00424.x
A. P. Heintz, F. Odicino, P. Maisonneuve, et al., “Carcinoma of the Ovary. FIGO 6th Annual Report on the Results of Treatment in Gynecological Cancer,” International Journal of Gynecology & Obstetrics, Vol. 95, No. 1, 2006, pp. S161-S192. doi:10.1016/S0020-7292(06)60033-7
P. Harter and A. du Bois, “The Role of Surgery in Ovarian Cancer with Special Emphasis on Cytoreductive Surgery for Recurrence,” Current Opinion in Oncology, Vol. 17, No. 5, 2005, pp. 505-514. doi:10.1097/01.cco.0000174166.06734.c7
G. Ferrandina, F. Legge, V. Salutari, et al., “Impact of Pattern of Recurrence on Clinical Outcome of Ovarian Cancer Patients: Clinical Considerations,” European Journal of Cancer, Vol. 42, No. 14, 2006, pp. 2296-2302. doi:10.1016/j.ejca.2006.03.025
T. J. Herzog, “The Current Treatment of Recurrent Ovarian Cancer,” Current Oncology Reports, Vol. 8, No. 6, 2006, pp. 448-454. doi:10.1007/s11912-006-0074-9
M. Markman, “Recurrence within 6 Months of Platinum Therapy: An Adequate Definition of “Platinum-Refractory” Ovarian Cancer?” Gynecologic Oncology, Vol. 69, No. 2, 1998, pp. 91-92. doi:10.1006/gyno.1998.4997
M. Markman, R. Rothman, T. Hakes, et al., “Second-Line Platinum Therapy in Patients with Ovarian Cancer Previously Treated with Cisplatin,” Journal of Clinical Oncology, Vol. 9, No. 3, 1991, pp. 389-393.
M. A. Bookman, H. Malmstrom, G. Bolis, A. Gordon, A. Lissoni, J. B. Krebs and S. Z. Fields, “Topotecan for the Treatment of Advanced Epithelial Ovarian Cancer: An Open-Label Phase II Study in Patients Treated after Prior Chemotherapy That Contained Cisplatin or Carboplatin and Paclitaxel,” Journal of Clinical Oncology, Vol. 16, No. 10, 1998, pp. 3345-3352.
G. J. Creemers, G. Bolis, M. Gore, G. Scarfone, A. J. Lacave, J. P. Guastalla, et al., “Topotecan, an Active Drug in the Second-Line Treatment of Epithelial Ovarian Cancer: Results of a Large European Phase II Study,” Journal of Clinical Oncology, Vol. 14, No. 12, 1996, pp. 3056-3061.
J. D. Shapiro, M. J. Millward, D. Rischin, M. Michael, V. Walcher, P. A. Francis, et al., “Activity of Gemcitabine in Patients with Advanced Ovarian Cancer: Responses Seen Following Platinum and Paclitaxel,” Gynecologic Oncology, Vol. 63, No. 1, 1996, pp. 89-93. doi:10.1006/gyno.1996.0284
B. Lund, O. P. Hansen, K. Theilade, M. Hansen and J. P. Neijt, “Phase II Study of Gemcitabine (2’,2’-Difluorodeoxycytidine) in Previously Treated Ovarian Cancer Patients,” Journal of the National Cancer Institute, Vol. 86, No. 20, 1994, pp. 1530-1533. doi:10.1093/jnci/86.20.1530
F. M. Muggia, J. D. Hainsworth, S. Jeffers, P. Miller, S. Groshen, M. Tan, et al., “Phase II Study of Liposomal Doxorubicin in Refractory Ovarian Cancer: Antitumor Activity and Toxicity Modification by Liposomal Encapsulation,” Journal of Clinical Oncology, Vol. 15, No. 3, 1997, pp. 987-993.
E. Bajetta, A. Di Leo, L. Biganzoli, L. Mariani, F. Cappuzzo, M. Di Bartolomeo, et al., “Phase II Study of Vinorelbine in Patients with Pretreated Advanced Ovarian Cancer: Activity in Platinum-Resistant Disease,” Journal of Clinical Oncology Vol. 14, No. 9, 1996, pp. 2546-2551.
P. J. Hoskins and K. D. Swenerton, “Oral Etoposide Is Active against Platinum Resistant Epithelial Ovarian Cancer,” Journal of Clinical Oncology, Vol. 12, No. 1, 1997, pp. 60-63.
P. G. Rose, J. A. Blessing, A. R. Mayer and H. D. Homesley, “Prolonged Oral Etoposide as Second-Line Therapy for Platinum-Resistant and Platinum-Sensitive Ovarian Carcinoma: A Gynecologic Oncology Group Study,” Journal of Clinical Oncology, Vol. 16, No. 2, 1998, pp. 405-410.
G. P. Sutton, J. A. Blessing, H. D. Homesley, M. L. Berman and J. Malfetano, “Phase II Trial of Ifosfamide and Mesna in Advanced Ovarian Carcinoma: A Gynecologic Oncology Group Study,” Journal of Clinical Oncology, Vol. 7, No. 11, 1989, pp. 1672-1676.
J. B. Vermorken, A. Kobierska, M. E. van der Burg, B. Chevallier, F. Zanaboni, W. W. ten Bokkel Huinink, et al., “High-Dose Epirubicin in Platinum-Pretreated Patients with Ovarian Carcinoma: The EORTC-GCCG Experience,” European Journal of Gynaecological Oncology, Vol. 16, No. 6, 1995, pp. 433-438.
D. S. Alberts, “Treatment of Refractory and Recurrent Ovarian Cancer,” Seminars in Oncology, Vol. 1, No. 1, 1999, pp. 8-14.
M. Harries and M. Gore, “Chemotherapy for Epithelial Ovarian Cancer-Treatment of Recurrent Disease,” Lancet Oncology, Vol. 3, No. 9, 2002, pp. 537-545. doi:10.1016/S1470-2045(02)00847-1
M. Markman, K. Webster, K. Zanotti, B. Kulp, G. Peterson and J. Belinson, “Phase II Trial of Single Agent Gemcitabine in Platinum-Paclitaxel Resistant Ovarian Cancer,” Gynecologic Oncology, Vol. 90, No. 3, 2003, pp. 593-596. doi:10.1016/S0090-8258(03)00399-8
A. N. Gordon, C. O. Granai, P. G. Rose, J. Hainsworth, A. Lopez, C. Weissman, et al., “Phase II Study of Liposomal Doxorubicin in Platinum- and Paclitaxel-Refractory Epithelial Ovarian Cancer,” Journal of Clinical Oncology, Vol. 18, No. 7, 2000, pp. 3093-3100.
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,” Journal of Clinical Oncology, Vol. 19, No. 14, 2001, pp. 3312-3322.
W. Zoli, L. Ricotti, F. Barzanti, M. Dal Susino, G. L. Frassineti, C. Milandri, et al., “Schedule-Dependent Interaction of Doxorubicin, Paclitaxel and Gemcitabine in Human Breast Cancer Cell Lines,” International Journal of Cancer, Vol. 80, No. 3, 1999, pp. 413-416.
A. B. Miller, B. Hoogstraten, M. Staquet and A. Winkler, “Reporting Results of Cancer Treatment,” Cancer, Vol. 47, No. 1, 1981, pp. 207-214.
P. Armitage, G. Berry and J. N. S. Mathews, “Statistical Methods in Medical Research,” 4th Edition, Blackwell Sciences Ltd, Oxford, 2002. doi:10.1002/9780470773666
E. Kaplan and P. Meier, “Nonparametric Estimation from Incomplete Observations,” Journal of the American Statistical Association, Vol. 53, 1958, pp. 457-481. doi:10.2307/2281868
P. Zola and A. Ferrero, “Is Carboplatin-Paclitaxel Combination the Standard Treatment of Elderly Ovarian Cancer Patients?” Annals of Oncology, Vol. 18, No. 2, 2007, pp. 213-214. doi:10.1093/annonc/mdl483
M. Harries and M. Gore, “Chemotherapy for Epithelial Ovarian Cancer—Treatment at First Diagnosis,” Lancet Oncology, Vol. 3, No. 9, 2002, pp. 529-536.
A. Du Bois, H. J. Luck, T. Bauknecht, V. Mobus, H. Bochtler, K. Diergarten, et al., “Phase I/II Study of the Combination of Carboplatin and Paclitaxel as First-Line Chemotherapy in Patients with Advanced Epithelial Ovarian Cancer,” Annals of Oncology, Vol. 8, No. 4, 1997, pp. 355-361. doi:10.1023/A:1008267419453
D. G. Mutch, M. Orlando, T. Goss, M. G. Teneriello, A. N. Gordon, S. D. McMeekin, et al., “Randomized Phase III Trial of Gemcitabine Compared with Pegylated Liposomal Doxorubicin in Patients with Platinum-Resistant Ovarian Cancer,” Journal of Clinical Oncology, Vol. 25, No. 19, 2007, pp. 2811-2818.
B. Lund, O. P. Hansen, K. Theilade, M. Hansen and J. P. Neijt, “Phase II Study of Gemcitabine in Previously Treated Ovarian Cancer Patients,” Journal of the National Cancer Institute, Vol. 86, No. 20, 1994, pp. 1530-1533. doi:10.1093/jnci/86.20.1530
J. D. Shapiro, M. J. Millward, D. Rishin, M. Michael, V. Walcher, P. A. Francis and G. C. Toner, “Activity of Gemcitabine in Patients with Advanced Ovarian Cancer: Responses Seen Following Platinum and Paclitaxel,” Gynecologic Oncology, Vol. 63, No. 1, 1996, pp. 89-93. doi:10.1006/gyno.1996.0284
K. U. Chow, J. Ries, E. Weidmann, F. Pourebrahim, S. Napieralski, M. Stieler, et al., “Induction of Apoptosis Using 2’,2’-Difluorodeoxycytidine (Gemcitabine) in Combination with Antimetabolites or Antracyclines on Malignant Lymphatic and Myeloid Cells. Antagonism or Symergism Depends on Incubation Schedule and Origin of Neoplastic Cells,” Annals of Hematology, Vol. 79, No. 9, 2000, pp. 485-492. doi:10.1007/s002770000181
B. A. Goff, T. Thompson, B. E. Greer, A. Jacobs and B. Storere, “Treatment of Recurrent Platinum Resistant Ovarian or Peritoneal Cancer with Gemcitabine and Doxorubicin: A Phase I/II Trial of the Puget Sound Oncology Consortium (PSOC 1602),” American Journal of Obstetrics and Gynecology, Vol. 188, No. 6, 2003, pp. 1556-1564. doi:10.1067/mob.2003.398
V. Murgia, O. Caffo, R. Sorio, C. Griso, A. Scalone, A. Ferro, et al., “Gemcitabine (G) and Epirubicin (E) Combination, in Platinum-Resistant or Refractory Advanced Ovarian Cancer (PROC) Patients: Results of a Multicentric Phase II Trial,” Journal of Clinical Oncology, Vol. 26, No. 15, 2008, p. 5566.
P. Chu, C. H. Lu, X. G. Sheng, C. X. Zhou, D. P. Li, X. L. DU and N. F. Liu, “Gemcitabine Based Combination Chemotherapy, a New Salvage Regimen for Recurrent Platinum Resistant Epithelial Ovarian Cancer,” Zhonghua Fu Chan Ke Za Zhi, Vol. 45, No. 11 2010, pp. 808-812.
E. Galligioni, C. Arcuri, R. Sorio and C. Griso, “Gemcitabine and Anthracyclines in Platinum-Resistant Ovarian Cancer,” Annals of Oncology, Vol. 17, No. 5, 2006, pp. 195-198.