Use of an ATP-based chemosensitivity assay to design new combinations of high-concentration doxorubicin with other drugs for recurrent ovarian cancer.
Liposomal doxorubicin (Caelyx/Doxil) has been shown to be active in around 20% of recurrent ovarian cancers. As yet, there is little clinical data on combinations of existing agents with liposomal doxorubicin, despite considerable clinical experience with soluble doxorubicin in combination. In this study, we have used an ATP-based tumor chemosensitivity assay to determine the relative efficacy of high concentrations of doxorubicin tested in combination with cisplatin, treosulfan, 5-fluorouracil (5-FU) or vinorelbine against cells obtained from recurrent ovarian tumor tissue. The results show little enhancement of the efficacy of high concentrations of doxorubicin by 5-FU, cisplatin, or treosulfan. However, vinorelbine+liposomal doxorubicin showed additive inhibition, and this combination is worthy of further testing in clinical trials.
Di Nicolantonio
Federica
F
Translational Oncology Research Centre, Michael Darmady Laboratory, Department of Histopathology, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK.
Neale
Michael H
MH
Knight
Louise A
LA
Lamont
Alan
A
Skailes
Geraldine E
GE
Osborne
Richard J
RJ
Allerton
Rosanne
R
Kurbacher
Christian M
CM
Cree
Ian A
IA
D000255:Adenosine Triphosphate; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D004337:Drug Carriers; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008081:Liposomes; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D014747:Vinblastine; D004317:Doxorubicin; D000255:Adenosine Triphosphate; C018404:treosulfan; D002066:Busulfan; D002945:Cisplatin; D000077235:Vinorelbine