Phase II study of the combination of pegylated liposomal doxorubicin and topotecan in platinum-resistant ovarian cancer

Abstract

The combination of liposomal doxorubicin and topotecan was evaluated in a phase II study in patients with platinum-resistant ovarian cancer. Twenty-seven patients received liposomal doxorubicin (30 mg/m(2)) infused at day 1, followed by topotecan (1 mg/m(2)) infusion daily for 5 days. Cycles were repeated every 21 days. This combination regimen showed an overall response rate of 28%. Median time to progression was 30 weeks, with a median overall survival of 40 weeks. Grade 3/4 neutropenia was shown in 70% of patients and grade 3/4 thrombopenia in 41% of patients. Neutropenic fever was reported in 11% of patients. After reviewing the first 12 patients, the internal review board decided to administer topotecan at a dose of 0.75 mg/m(2) and liposomal doxorubicin at 40 mg/m(2) for the remainder of the study. However, this adjustment did not lead to reduction in bone marrow toxicity nor to an improvement in dose intensity. Palmar-plantar erythrodysesthesia and mucositis were more reported in the second cohort but usually mild. The combination of liposomal doxorubicin and topotecan demonstrates favorable response data in platinum-resistant ovarian cancer. However, substantial bone marrow toxicity limits further clinical use.

Second-Line Chemotherapy for Platinum- and Taxane-Resistant Epithelial Ovarian Cancer: Pegylated Liposomal Doxorubicin (PLD), Irinotecan, and Combination Therapies at Lower Doses

“…24) A median total response rate of 28% and clinical benefit of 72% were demonstrated, with a median TTP of 30+weeks in the combination of PLD and topotecan for platinum-resistant disease (Table 3). 25) These data compare favorably to the data of both the drugs administered as single agent. In comparison of two studies of combination chemotherapy of PLD and oxaliplatin, the response rates for platinum-resistant disease were 28.6% and 38.5% and the clinical benefit was 71.4% and 76.9%, suggesting the higher efficacy compared with PLD monotherapy.…”

Pegylated Liposomal Doxorubicin for Advanced Ovarian Cancer in Women who are Refractory to Both Platinum- and Paclitaxel-Based Chemotherapy Regimens

“…32,33 A median total response rate of 28% and clinical benefit of 72% were demonstrated, with a median TTP of 30+ weeks in the combination of PLD and topotecan for platinum-resistant disease (Table 4). 34 These data compare favorably to the data of both drugs administered as a single agent. Combination chemotherapy of PLD and GEM achieved good response rates ranging from 22% to 33%; however, the clinical benefit was between 28% and 61%, which was similar to PLD monotherapy.…”

A Phase I Study of Oral Topotecan and Pegylated Liposomal Doxorubicin (Doxil) in Platinum-Resistant Ovarian and Peritoneal Cancer

“…Therefore, the activity of this regimen was consistent with that reported in previous studies of this combination. 24,25 Indeed, only 5 patients completed Ͼ4 cycles of therapy because of hematologic toxicities. Also consistent with the previous report of Mirchandani et al, 24 combination therapy with oral topotecan and PLD was associated with dose-limiting myelosuppression.…”