Efficacy of cisplatin combined with topotecan in patients with advanced or recurrent ovarian cancer as second- or higher-line palliative chemotherapy.

The aim of this study was to evaluate the outcomes of patients with advanced or recurrent ovarian cancer treated with cisplatin combined with topotecan as second- or higher-line palliative chemotherapy.We retrospectively reviewed the medical records of patients with advanced or recurrent ovarian cancer, who were treated with cisplatin (50 mg/m on day 1) and topotecan (0.75 mg/m on days 1-3). Treatment response, progression-free survival (PFS) and overall survival (OS) were analyzed, and laboratory data were reviewed to evaluate toxicities.Thirty one patients were treated with cisplatin and topotecan. The objective response rate (ORR) was 22.6%, and the disease control rate (DCR) was 61.3%. The median PFS was 3.7 months (95% confidence interval [CI], 2.3-5.2 months) and the median OS was 44.5 months (95% CI, 35.5-53.5 months). The ORR (33.3% vs. 0%; P = .012) was significantly better in the platinum-sensitive group compared to the platinum-resistant group. The median PFS was significantly longer in the platinum-sensitive group compared to the platinum-resistant group (7.7 vs 2.5 months; P < .001), and the median OS was also significantly longer in the platinum-sensitive group (46.6 vs 19.3 months; P < .001). Almost all of the patients reported some degree of hematological toxicity. A high rate of grade 3-4 neutropenia (87.1%) was observed. Grade 3-4 thrombocytopenia (41.9%) and febrile neutropenia (19.4%) were also seen.The results showed that cisplatin combined with topotecan, as second- or higher-line palliative chemotherapy for patients with advanced or recurrent ovarian cancer, might be effective, especially in the platinum-sensitive group. However, attention should be paid to the high hematological toxicity associated with this drug combination.

Weekly topotecan: an alternative to topotecan's standard daily x 5 schedule?

Relapsed ovarian cancer and small cell lung cancer are frequently treated with topotecan (Hycamtin), for which the standard dose and schedule are 1.5 mg/m(2) daily for five consecutive days every 3 weeks. Clinical experience has shown that this dose and schedule may be too toxic for some patients, especially those who have been heavily pretreated with platinum-based therapeutics, and it has been suggested that starting doses of topotecan be reduced to 1.0-1.25 mg/m(2)/d. Recently, multiple clinical trials have begun to evaluate the feasibility and preliminary antitumor activity of an alternative schedule based on weekly administration of topotecan. The potential benefits of weekly administration include not only reduced toxicity without significant compromise of antitumor activity, but also greater patient convenience and quality of life and greater potential for developing new topotecan-containing combination therapies. This report reviews the rationale for a weekly schedule, as well as a growing base of emerging clinical data. These preliminary data suggest that weekly topotecan is active; further evaluations are planned to confirm the activity and therapeutic index and to determine optimal dosing of a weekly schedule.

Results of topotecan-based combination therapy in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.

The efficacy and safety of topotecan and high-dose cytarabine were evaluated in 59 patients with advanced myelodysplastic syndromes (MDS) (n = 38) or chronic myelomonocytic leukemia (CMML) (n = 21). Topotecan 1.25 mg/m2/d was administered by continuous Intravenous infusion daily for 5 days, and cytarabine 1.0g/m2/d by Infusion over 2 hours for 5 days. At a median follow-up duration of 7 months, 59 patients were evaluable for response and toxicity. Complete remission (CR) was achieved in a significantly larger proportion of MDS patients than CMML patients (66% v 48%, P < or = .05). CR rates for good-risk and poor-risk MDS patients were similar (79% and 58%, respectively). Treatment was particularly effective in patients with poor-prognosis karyotypes and secondary MDS, producing CR rates of 63% and 69%, respectively. Medlan duration of CR was 32 weeks (41 weeks for MDS; 33 weeks for CMML). Median survival was 60 weeks for MDS patients and 41 weeks for CMML patients. Prospective analysis of response by International Prognostic Scoring System (IPSS) risk classification showed comparable CR rates among intermediate 1 (60%), Intermediate 2 (83%), and high-risk (56%) categories. Fever of undetermined origin and Infections occurred in 72% and 59% of patients, respectively. Six patients (10%) died during Induction therapy. This regimen was well tolerated and was associated with a low mortality rate.