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{TANDF_FPP}CMO/CMO_A_370883(NEW).3d (CMO) [First Proof]
Current Medical Research and Opinion
C213
Volume 25, Number 3 2008
Table 1. Randomized phaseIII trials of first-line topotecan in patients with ovarian cancer.
Study Strategy Regimen Patients (n) RR (%) TTP (weeks) Survival (months)
Scarfone et al., Triplet CP vs. TCP 170 85.2 70.4 —
2006
44
* 156 92.5 71.8
Pfisterer et al., Consolidation CP vs. CP!T 650 76.2 — 44.5
2005
45
658 69 43.1 (OS)
Hoskins et al., Sequential CP vs. CT!CP 410 — — 16.2
2008
11
* 409 14.6 (PFS)
De Placido et al., Sequential CP vs. CP!T 136 — — 28.4
2004
46
137 18.2 (PFS)
Bookman et al., Doublets CP 864 — — 16.1 40.0
2006
47
* CPG 864 16.4 40.0
CPD 862 16.4 42.8
CT!CP 861 15.3 39.1
CG!CP 861 15.4 (PFS) 40.2 (OS)
C: carboplatin; P: paclitaxel; T: topotecan; G: gemcitabine; D: docetaxel; OS: overall survival; PFS: progression-free survival; TTP: time to progression;
RR: response rate.
*Preliminary clinical trial results presented at ASCO.
tolerability of topotecan with other effective agents topotecan and PLDH,respectively (p¼0.39). Overall sur-
in relapsed ovarian cancer (Table 2)
3,4
. vival was significantly greater with PLDH than topotecan
The first phase III trial to compare topotecan with (27 vs. 17.8 months; p¼0.008) in platinum-sensitive
an existing therapy was performed by ten Bokkel patients. However, survival was comparable in patients
and colleagues
19,20
. A total of 226 patients who had with platinum-refractory disease. Median survival was
failed first-line platinum-based therapy were randomized also similar, at 10.3 months for topotecan and 8.9
to treatment with i.v. topotecan 1.5mg/m
2
/day 1–5 every months for PLDH (p¼0.455). The number of grade1, 2,
21 days, or paclitaxel 175mg/m
2
every 21 days. Response and 3 adverse events was similar between the two treat-
rates in the paclitaxel and topotecan arms were 20.5% and ment arms; however, grade4 adverse events were signifi-
13.2%, respectively (p¼0.138). Neutropenia was the cantly more frequent with topotecan. The most common
major haematological toxicity associated with both treat- adverse events associated with topotecan were haemato-
ments; grade4 neutropenia occurred in 79% of patients logical (largely neutropenia), while a large number of
and 37% of courses with topotecan therapy, compared patients receiving PLDH experienced palmar–plantar ery-
with 23% of patients and 9% of courses in the paclitaxel throdysaesthesia (PPE) (49%) and stomatitis (40%).
treatment arm. Although haematological toxicity was Haematological toxicity in the topotecan arm resulted in
more frequent with topotecan, it was of short duration agreater utilizationofhaematopoietic growthfactors com-
and non-cumulative. In addition, clinical sequelae were pared with PLDH (29.1vs. 4.6%)
21
.
relatively infrequent due to the use of dose reduction or Overall, the results of the above phase III trials indicate
granulocyte colony-stimulating factor (G-CSF) (prophy- thati.v.topotecanisaseffectiveaspaclitaxelandPLDHin
lactic G-CSF was administered to maintain dose intensity the treatment of ovarian cancer. In addition, i.v. topote-
in 23% of topotecan courses and in 3% of paclitaxel can lacked cross-resistance to both paclitaxel
19,20
and
courses, while treatment G-CSF was given in 7% of PLDH
21
, and showed almost no overlapping or cumulative
topotecan courses and 1% of paclitaxel courses). Non- toxicity
19
. Preliminary results of a further phase III trial
haematological toxicities reported in both treatment demonstrate that topotecan has superior progression-free
arms were generally mild and not dose-limiting
19,20
. survival rates compared with treosulphan in patients with
Also, QoL, as assessed by the European Organization for relapsed ovarian cancer (p50.0001)
22
(Table 2).
Research and Treatment of Cancer (EORTC) QoL-C30 Topotecan is currently available as an i.v. preparation;
questionnaire,wasreportedtobesimilarinpatientsreceiv- however, an oral formulation of topotecan has shown clin-
ing topotecan and paclitaxel
19
. ical promise in several clinical trials
24–26
. In a randomized
The activity of i.v. topotecan has also been compared study of 266 patients with relapsed ovarian cancer, median
with that of PLDH. In a randomized phase III trial
21
, 474 survival time in the i.v. arm was significantly greater than
patients with epithelial ovarian carcinoma that recurred the oral topotecan arm (58vs. 51 weeks; p¼0.033)
25
. The
after or did not respond to first-line therapy were treated reportedincidenceofgrade3/4neutropeniawaslowerwith
with either i.v. topotecan 1.5mg/m
2
/day 1–5 every the oral formulation
25
; however, severe fatigue was more
3 weeks, or PLDH 50mg/m
2
as a 1-hour infusion every common. Thus, further studies are required to define the
4 weeks. Median overall response rates were comparable best dose and regimen for oral topotecan. Preliminary
between the two treatment arms, 17% and 19.7% for results of a study that assessed oral topotecan when
!
2009 Informa UK Ltd
www.cmrojournal.com Topotecan for relapsed ovarian cancer Sehouli & Oskay-O
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zcelik
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