XML Template (2009) [5.9.2009–3:06pm] [1–12]
{TANDF_FPP}CMO/CMO_A_370883(NEW).3d (CMO) [First Proof]
Current Medical Research and Opinion
C213
Volume 25, Number 3 2008
(TOMEGROC) from the German NOGGO study group and thereby limit its impact on patients’ QoL. Data from
assessed non-platinum topotecan combinations versus several phase I and phase II clinical trials that investigated
topotecan alone, in relapsed ovarian cancer. A total of administration of i.v. bolus topotecan on a weekly basis
502 patients were randomly assigned to topotecan mono- produced encouraging results; this schedule is anticipated
therapy1.25mg/m
2
/day,topotecan1.0mg/m
2
/dayandoral to have less toxicity than the current standard 5-day regi-
etoposide50mg/day,ortopotecan0.5mg/m
2
/dayandgem- men. The interim results of the TOWER study, an
citabine800mg/m
2
onday1and600mg/m
2
onday8every ongoing, large phase II clinical trial, have recently been
3 weeks. The results showed that non-platinum topotecan reported at ASCO. They showed that weekly topotecan
combinations do not provide a survival advantage over seems to be an active regimen with less haematotoxicity
topotecan monotherapy in patients with relapsed ovarian compared with the standard 5-day regimen. The final
cancer
43
. In this trial, topotecan monotherapy offered the results of the NOGGO-TOWER study, which has mean-
best therapeutic index. while completed recruitment, are planned for 2009.
Combination studies of topotecan with existing thera-
pies, including PLDH, paclitaxel, gemcitabine, and carbo-
Combination with targeted therapies
platin, have shown encouraging results in a number of
A novel approach to treating ovarian cancer involves the
phaseIIclinicaltrialsofpatientswithprimaryandrelapsed
use of agents which target specific pathways that are
ovarian cancer. Data from clinical trials of topotecan in
alteredinmalignantcells.Agentsthathaveshownclinical
combination with targeted therapies, including thalido-
promise when used as single-agent monotherapy include
mide, bevacizumab, erlotinib, and lapatinib, are also pro-
bevacizumab, erlotinib, thalidomide and lapatinib.
mising and warrant further investigation in more
Preliminary reports for a number of recent phase I and
extensive, phase III trials.
phase II trials in patients with ovarian cancer have indi-
This narrative review is based on references obtained
cated potential additional therapeutic benefits when tar-
from a literature search of the MEDLINE database. To
geted therapies are combined with topotecan (Table 5).
increase the robustness of our conclusions, we also
Further phase III trials with intensive translational
includedrelevantarticlesfromthereference listsofrelated
research projects are warranted to define the definitive
papers and recent review articles, as well as abstracts from
role of such combinations.
ASCO meetings. We feel that this review provides a thor-
ough analysis of presently available literature concerning
the current use and future role of topotecan in primary and
Discussion
relapsedovariancancer.Whilethecongressabstractscited
inthisreviewprovideresultsofthemostup-to-datestudies
Most patients with ovarian cancer respond to first-line
oftopotecan,itshouldbenotedthatthesereportshavenot
treatment with the current gold-standard regimen of car-
been peer-reviewed, and thus care should be taken when
boplatin and paclitaxel, but the majority subsequently
interpreting these data.
experience disease relapse. Literature searches identified
a number of peer-reviewed articles and congress abstracts
reportingtheresultsofstudies thatincorporated topotecan
into the gold-standard regimen, in an attempt to circum-
Conclusions
vent platinum resistance and improve clinical outcomes.
Analysis ofthe peer-reviewed literature suggests thattopo-
Data from these clinical trials do not support the use of
tecan is an effective, well tolerated treatment option for
topotecan as first-line therapy.
relapsed ovarian cancer. Different schedules of topotecan
Asmentionedabove,mostpatientswithovariancancer
are currently under investigation. Administration of topo-
relapse. Treatment options for patients with relapsed ovar-
tecan on a weekly basis in patients with relapsed disease
ian cancer are currently limited. Consequently, the main
has produced encouraging results in a number of phase II
aims of treatment are maintenance of QoL combined with
trials. Further large-scale trials are therefore warranted to
prolonged survival. Topotecan is an established treatment
determine the clinical relevance of these results.
option in the relapsed setting. Peer-reviewed articles
report the standard 5-day regimen of topotecan is an
intense regimen with good clinical efficacy in both plati-
num-sensitive and platinum-resistant relapsed ovarian
Acknowledgements
cancer. Associated haematological toxicity of topotecan
Declaration of interest
is predictable, generally manageable, reversible and non-
This article was supported by GlaxoSmithKline. J. S. and
cumulative. Literature searches identified a number of
G. O-O. participate as investigators on several trials for
alternative dosing regimens, which are being investigated
GlaxoSmithKline and Eli Lilly and Company. The institution
in an attempt to improve the toxicity profile of topotecan, of the corresponding author received study funding from
10
Topotecan for relapsed ovarian cancer Sehouli & Oskay-O
¨
zcelik
www.cmrojournal.com
!
2009 Informa UK Ltd
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