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
C15 Weekly 72-hour continuous i.v. infusion
35
toxicities, and offer flexible dosing and scheduling.
C15 Weekly 24-hour continuous i.v. infusion
35
As detailed previously, topotecan administered on a
C15 Weekly i.v. bolus regimens
35
weekly basis is associated with less toxicity compared
Most of these regimens had less haematological toxi- with the standard 5-day regimen of topotecan.
city, but varied in their anti-tumour activity and conve- Weekly administration of topotecan may therefore be a
nience of administration. The once-weekly dosing promising future regimen for the treatment of ovarian
regimen seems to be the most promising schedule to cancer. Nevertheless, no randomized studies have so far
improve the therapeutic index of i.v. topotecan. been performed in patients with ovarian cancer. An
Weekly i.v. bolus topotecan has produced encouraging attempt by the American Gynecologic Oncology Group
results in both preclinical experiments and in clinical
(GOG) in platinum-sensitive patients failed, due to slow
trials, among patients with a wide range of different
recruitment; the study was thus terminated early. The
tumours, including ovarian (Table 3)
7,34
. Homesley et al.
North Eastern German Society of Gynecological
were the first to assess weekly i.v. bolus topotecan in a
Oncology (NOGGO) has conducted an open-label
dose-escalating phase I/II study
36
. The maximum tolerated
phase II trial (the TOWER study) to compare weekly
dose without the use of G-CSF was 4mg/m
2
; at doses of at
versus standard 5-day regimen topotecan in patients with
least 2mg/m
2
/week, 13% of patients demonstrated a par-
platinum-resistant ovarian disease. The planned interim
tialresponse and19%achievedstable disease. Inaphase II
results were presented at the 2007 annual ASCO meeting.
study in patients with platinum-sensitive, recurrent ovar-
The interim analysis met the predetermined efficacy and
ian cancer, weekly i.v. topotecan elicited a complete
toxicity milestones. Meanwhile, recruitment was success-
response in 3% of patients, a partial response in 21% of
fully completed
42
. Final results are expected in 2009.
patients and stable disease in a further 42% of patients
35
.
The weekly i.v. regimen was also associated with improved
toxicity compared with daily i.v. topotecan: grade3 or 4
Topotecan combination therapy
neutropeniaoccurredin17%oftreatments,andtherewere
no reports of grade4 thrombocytopenia, leucopenia or
Topotecan has been combined with a variety of other
anaemia
35
. Two additional phase II studies in patients
cytotoxic agents in the first- and second-line treatment
with sensitive disease have also demonstrated lower toxi-
of patients with ovarian cancer
4
. These include: gemcita-
city with weekly topotecan than with 3-weekly
bine, PLDH, paclitaxel, ifosfamide, cyclophosphamide,
topotecan
23,37
.
etoposide, carboplatin, and oxaliplatin. A number of
Weekly i.v. topotecan has also shown encouraging
phase II studies of topotecan in combination with the
results in patients with platinum-resistant, recurrent ovar-
aforementioned cytotoxic agents have yielded encoura-
ian cancer (Table 3). In phase II studies, weekly adminis-
ging results (Table 4). The NOGGO-AGO intergroup
tration of topotecan was associated with a reduction in
study HECTOR (Hycamtin and Carboplatin vs.
haematological toxicity when compared with standard
Established Regimens for the Treatment of Ovarian
topotecan regimens
38–40
. The results of a number of retro-
Cancer Relapse) for platinum-sensitive patients, which is
spective analyses of patients with relapsed ovarian cancer
assessing topotecan plus carboplatin in a 3-day schedule in
showed that weekly i.v. topotecan is generally well
comparison with the current standard, is ongoing. In this
tolerated, with milder haematological toxicities than the
study, choice of the control arm can be between paclitaxel
standard daily regimen. Anti-tumour efficacy was demon-
plus carboplatin or gemcitabine plus carboplatin, based on
strated even in patients who had been heavily pretreated,
late toxicity (e.g., polyneuropathy) and patients’ prefer-
and who therefore might require dosing schedules with
ences (e.g., alopecia).
improved tolerability
7,41
.
So far, only two phase III studies have been published
Availability of a weekly i.v. regimen of topotecan may
that assessed the efficacy and safety of topotecan combina-
reduce the need for dose reductions, haematopoietic
tion therapy in patients with ovarian cancer. In the first
growth factor administration, and blood product support
study,which is at the preliminary reporting stage,a total of
compared with the standard 5-day regimen
18
. In addition
819 women with newly diagnosed ovarian cancer were
to improving the toxicity profile of topotecan, a weekly randomized to one of two 21-day regimens: arm1 –
schedule also offers added convenience to patients with cycles1–4 cisplatin 50mg/m
2
day1 plus topotecan
relapsed ovarian cancer receiving combination treatment 0.75mg/m
2
i.v. on days 1–5, cycles 5–8 paclitaxel
withotheragentsadministeredinweeklyregimens,suchas 175mg/m
2
over 3hours on day1, followed by carboplatin
paclitaxel
32
.Agoodrationalethereforeexistsfortheuseof AUC5 on day1; arm2 – paclitaxel plus carboplatin as in
the weekly topotecan regimen in patients with ovarian arm1 for 8cycles. The results indicated that topotecan/
cancer
4
. cisplatin followed by carboplatin/paclitaxel was more
Asignificant need exists fortherapies that areeffective, toxic and did not show any evidence of improved efficacy
well tolerated, exhibit no progressively worsening compared with standard therapy
11
. The second study
6
Topotecan for relapsed ovarian cancer Sehouli & Oskay-O
¨
zcelik
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2009 Informa UK Ltd
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