Medline ® Abstracts for References 25-27
Weekly combination of topotecan and gemcitabine in early recurrent ovarian cancer patients: a French multicenter phase II study.
Joly F, Petit T, Pautier P, Guardiola E, Mayer F, Chevalier-Place A, Delva R, Sevin E, Henry-Amar M, Bourgeois H
Gynecol Oncol. 2009;115(3):382. Epub 2009 Sep 20.
OBJECTIVES: The aim of this phase II study was to assess the benefits of a weekly administration of topotecan and gemcitabine in patients with ovarian carcinoma having relapsed after platinum/taxane-based first-line chemotherapy.
METHODS: Seventy-seven patients with progression of disease</=12 months after first-line chemotherapy were enrolled to receive topotecan (2.5 mg/m(2)) and gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 (q 28 d). Primary endpoint was the response rate. Stabilization rate and symptom improvement were also assessed.
RESULTS: All patients received the combination and 66 were evaluable (>/=2 cycles administered). The only major severe toxicity was neutropenia grades 3 (17%) and 4 (6%). Approximately 60% of the patients received the complete schedule of treatment, dose interruptions/delays being mainly due to moderate thrombocytopenia or neutropenia. The objective response rate was 14%, the values for patients having relapsed within 6 (n=30) and 6-12 (n=36) months being 7%and 20%, respectively. Median durations of response were 4.9 and 6.4 months and clinical benefit rates including stabilizations reached 63% and 69% in patients having relapsed within 6 or 6-12 months, respectively. Corresponding median overall survival was 7.5 and 15.6 months. Symptoms and pain were reduced in 64% and 39% of the patients concerned, respectively.
CONCLUSION: In early relapse ovarian cancer, weekly combination of gemcitabine and topotecan has a modest objective response rate. However, a high proportion of patients experienced stable disease and symptom control leading to acceptable quality of life.
Centre François-Baclesse, avenue du Général Harris, 14076 Caen Cedex 5, France. firstname.lastname@example.org
Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer.
Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM
J Clin Oncol. 2010;28(19):3107. Epub 2010 Jun 1.
PURPOSE: The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.
PATIENTS AND METHODS: Women>or = 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m(2) followed by a 3-hour infusion of trabectedin 1.1 mg/m(2) every 3 weeks or PLD 50 mg/m(2) every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.
RESULTS: Patients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.
CONCLUSION: When combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.
University of California at Irvine (UCI) and UCI Medical Center, Orange, CA 92868-3298, USA. email@example.com
Biweekly vinorelbine and gemcitabine as second-line and beyond treatment in ovarian cancer.
Xenidis N, Neanidis K, Amarantidis K, Dimopoulos P, Chamalidou E, Pitsiava D, Tentes A, Chatzaki E, Karakitsos P, Kakolyris S
Cancer Chemother Pharmacol. 2011 Jan;67(1):69-73. Epub 2010 Mar 11.
PURPOSE: To evaluate the activity and tolerance of vinorelbine (VRL) in combination with gemcitabine (GEM) in pre-treated patients with refractory ovarian cancer.
PATIENTS AND METHODS: Seventeen patients with ovarian cancer who had disease progression after a carboplatin and taxane front-line regimen were treated with VRL 30 mg/m(2) IV over 10 min followed by GEM 1,200 mg/m(2) IV over 30 min on days 1 and 15 of each 28 days cycle. Chemotherapy was given in a initial prospective plan of six cycles, unless disease progression or unacceptable toxicity was seen, giving more cycles as consolidation therapy in the case of CR, PR or SD. The median age of patients was 67 years old, and the performance status (WHO) was 1 for 13 and 2 for 4 patients. The treatment was second-line for 11 (65%) and>third-line for 6 (35%) patients.
RESULTS: One complete and one partial response were observed (ORR:11%). Stable disease was seen in 4 (24%) patients and progressive disease in 11 (65%). The median time totumor progression was 4 months (range 2-11), and the median survival has not yet been reached. Myelotoxicity was rare. Grade 1 neutropenia was observed just in one patient and grade 2/3 anemia in four patients (24%). Thrombocytopenia was absent. Non-hematologic toxicity was also predictable and easily manageable.
CONCLUSION: The vinorelbine plus gemcitabine combination at the present doses and schedule is a safe but ineffective regimen, and therefore, is not recommended as second-line and beyond treatment in patients with refractory ovarian cancer.
Department of Medical Oncology, University General Hospital of Alexandroupolis, Dragana, 68100 Alexandroupolis, Thrace, Greece.