Medline ® Abstracts for References 17,18
A phase 2 study of oxaliplatin combined with continuous infusion topotecan for patients with previously treated ovarian cancer.
Stein SM, Tiersten A, Hochster HS, Blank SV, Pothuri B, Curtin J, Shapira I, Levinson B, Ivy P, Joseph B, Guddati AK, Muggia F
Int J Gynecol Cancer. 2013 Nov;23(9):1577-82.
BACKGROUND: Phase 2 trials suggest that prolonged intravenous (IV) infusion of the topoisomerase 1 inhibitor topotecan may be less toxic than when given by standard IV bolus 5-day administration. Oxaliplatin exhibits efficacy in platinum-pretreated disease and shows preclinical synergy with topoisomerase 1 inhibitors. We sought to determine the efficacy and safety of oxaliplatin plus infusion topotecan in recurrent platinum-pretreated ovarian cancer.
METHODS: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers previously treated with 1 to 2 prior regimens including platinum and taxane received oxaliplatin (85 mg/m(2) day 1 and day 15) and topotecan (0.4 mg/m(2) per day) by continuous IV infusion over 14 days every 4 weeks. The primary objective of the trial was to estimate the objective response rate in platinum-resistant disease (stratum 1) and in platinum-sensitive disease (stratum 2). Toxicities were assessed in all patients.
RESULTS: Thirty-eight patients received 144 cycles of therapy (median, 4; range, 1-6). The most common grade 3 and grade 4 toxicities included thrombocytopenia (grade 3, 37%; and grade 4, 19%), neutropenia (grade 3, 37%; grade 4, 11%), and anemia (grade 3, 15%). Response occurred in 4 of 19 patients in stratum I (21%; 95% confidence intervals, 6%-46%) and 9 of 19 patients in stratum 2 (47%; 95% CI, 24%-71%). Three in each stratum had lengthy complete responses.
CONCLUSIONS: Biweekly oxaliplatin plus a 14-day continuous IV infusion of topotecan, given monthly, is an active regimen in platinum-pretreated ovarian cancer and merits additional evaluation.
*Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT;†Division of Medical Oncology, Department of Medicine, and‡Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY;§Beth Israel Cancer Center, Albert Einstein College of Medicine, NY; New York University School of Medicine, New York, NY,∥Division of Biostatistics, Department of Population Health, New York University School of Medicine, New York, NY;¶Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and #Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Gemcitabine-oxaliplatin (GEMOX) as salvage treatment in pretreated epithelial ovarian cancer patients.
Vici P, Sergi D, Pizzuti L, Mariani L, Arena MG, Barba M, Maugeri-SaccàM, Vincenzoni C, Vizza E, Corrado G, Paoletti G, Tomao F, Tomao S, Giannarelli D, Di Lauro L
J Exp Clin Cancer Res. 2013 Aug;32(1):49. Epub 2013 Aug 8.
BACKGROUND: Currently, no clearly superior management strategy exists for recurrent, platinum-resistant ovarian cancer. We tested the efficacy and safety of gemcitabine combined with oxaliplatin (GEMOX) in a multicentre phase II clinical trial.
METHODS: Forty one patients with recurrent, platinum-resistant ovarian cancer were enrolled. Prior to study entry, all the participants had received at least one platinum-based regimen. Gemcitabine was administered at 1000 mg/m2 as protracted infusion (100 min) on day 1, and oxaliplatin at the dose of 100 mg/m2 on day 2 in a 2 hour infusion. Cycles were repeated every two weeks.
RESULTS: We observed an overall response rate of 37% [95% Confidence Interval (CI), 22.3--51.7]. Objective responses plus disease stabilization (clinical benefit) occurred in 78% of patients. Median progression-free survival was 6.8 months (95% CI, 5.8--7.8), and median overall survival was 16.5 months (95% CI, 12.2--20.8). Median time to self-reported symptom relief, which was described by 22 out of 27 symptomatic patients (81.5%), was 4 weeks (range, 2--8). Grade 4neutropenia and febrile neutropenia were observed in 2 (5%) and 1 (2.5%) patients, while grade 3 anemia was encountered in 2 (5%) patients, respectively. The most common adverse effects of any grade were gastrointestinal symptoms, fatigue and neutropenia. Nine patients (22%) experienced mild allergic reaction to oxaliplatin, with no treatment discontinuation.
CONCLUSIONS: In our cohort of recurrent, platinum-resistant ovarian cancer patients, GEMOX showed encouraging activity and manageable toxicity. Under circumstances requiring a rapid disease control, this combination regimen may offer a particularly viable option, particularly in heavily pretreated patients.