American Association for Cancer Research
10780432ccr122459-sup-f1_pdf_66k.pdf (66.52 kB)

Supplementary Figure 1 from Topotecan and Doxorubicin Combination to Treat Recurrent Ovarian Cancer: The Influence of Drug Exposure Time and Delivery Systems to Achieve Optimum Therapeutic Activity

Download (66.52 kB)
journal contribution
posted on 2023-03-31, 17:23 authored by Nilesh A. Patankar, Julia Pritchard, Mariska van Grinsven, Maryam Osooly, Marcel B. Bally

PDF file - 66 KB, Kaplan-Meier survival plot of Ncr-Nude mice bearing intraperitoneally grown ES-2 clear cell carcinoma xenografts after i.v treatment (q7d x 3) with free topotecan, Topophore C and Doxil either as single agents or in combination as shown shown. Data points represent mean � SD, (n � 6).



Purpose: To provide proof-of-concept data to support use of Doxil–liposomal topotecan (Topophore C) combinations to treat ovarian cancer.Experimental Design: ES-2, OVCAR-3, and SKOV-3 ovarian cancer cell lines were treated with doxorubicin–topotecan combinations by exposing the cells to drugs from 1 to 72 hours. Pharmacokinetic analysis was conducted following administration of liposomal formulations of these drugs alone and in combination. Efficacy assessments were completed in ES-2 and SKOV-3 ovarian cancer models.Results: On the basis of drug doses capable of achieving 50% reduction in cell viability over 72 hours, doxorubicin–topotecan combinations were additive in SKOV-3 but highly synergistic in ES-2 and OVCAR-3 cells. Favorable drug–drug interactions increased with increased drug exposure time. Topophore C pharmacokinetic remained unaffected when co-administered with Doxil. In the ES-2 model, Doxil at maximum tolerated dose (MTD 7.5 mg/kg) in combination with free topotecan (MTD 15 mg/kg) did not enhance median survival time (MST) over that achieved with topotecan alone. In contrast, MST was increased to 52 days with combination of Topophore C (MTD 2.5 mg/kg) and Doxil (7.5 mg/kg) compared with untreated animals (MST 18 days) or those treated with Topophore C alone (MTD 5 mg/kg, MST 40 days). In the SKOV-3 model, combination treatments showed better therapeutic efficacy than the individual drugs.Conclusions: Topotecan–doxorubicin combinations produced additive or synergistic effects which were best achieved when the tumor cells were exposed to drugs over extended time. Doxil–Topophore C combinations are therapeutically superior as judged in two ovarian cancer models. Clin Cancer Res; 19(4); 865–77. ©2012 AACR.

Usage metrics

    Clinical Cancer Research




    Ref. manager