Académique Documents
Professionnel Documents
Culture Documents
net/publication/320187911
CITATIONS READS
0 171
8 authors, including:
Some of the authors of this publication are also working on these related projects:
All content following this page was uploaded by Ahmed Abu-Zaid on 03 October 2017.
Ahmed Abu-Zaid1*, Marah Nayfeh1, Sana Almairi1, Nida Zubairi1, Aseel Eljabali1,
Mohammed Abuzaid2, Osama Alomar3 and Hany Salem1,3
1
College of Medicine, Alfaisal University, Saudi Arabia
2
Department of Obstetrics & Gynecology, King Fahad Medical City, Saudi Arabia
3
Department of Obstetrics & Gynecology, King Faisal Specialist Hospital and Research Centre,
Saudi Arabia
*Corresponding author: Ahmed Abu-Zaid, College of Medicine, Alfaisal University, P.O.
Box 50927, Riyadh 11533, Saudi Arabia, Tel: +966 567 566 622; Fax: +966 11 215 7611;
Email(s): aabuzaid@live.com & aabuzaid@alfaisal.edu
ABSTRACT
Epithelial ovarian cancer (EOC) is the fifth principal cause of cancer-related mortality in
women. Roughly 75% of women with EOC present with an advanced-stage disease, and the classical
first-line management is optimal cytoreduction (whenever technically feasible) followed by an
adjuvant platinum-based chemotherapy. In spite of the relatively high response rates to first-line
chemotherapy, around 70-85% of patients develop disease recurrence. These patients eventually
require an additional systemic medical treatment, and its selection is based on the platinum-
free interval (PFI) - that is, the time period from completion of platinum-based chemotherapy
to beginning of disease progression. Patients with a PFI greater than a time period of 6 months
are regarded as platinum-sensitive. The aim of study is to review the systemic chemotherapy
INTRODUCTION
Epithelial ovarian cancer (EOC) is the fifth principal cause of cancer-related mortality in
women [1]. It has been estimated that roughly 75% of women with EOC present with advanced-
stage disease (III-IV) which is associated with an unfortunate prognosis [2]. The classical first-line
management for advanced-stage disease is optimal cytoreduction (whenever technically feasible)
followed by an adjuvant platinum-based chemotherapeutic regimen [2,3]. In spite of the relatively
high response rates to first-line chemotherapy, around 70-85% of patients relapse, progress to
locally advanced unresectable or metastatic inoperable disease, or even develop drug-resistant
disease [2,4].
Patients with recurrent EOC will eventually require an additional systemic medical treatment.
The selection of systemic medical treatment is largely based on the response to the first-line
chemotherapy - that is, the platinum-free interval (PFI) [5]. The PFI is defined as the interval from
the completion of first-line platinum-based chemotherapy to the beginning of disease progression
[5]. Patients with a PFI less than or equal to a time period of 6 months are regarded as platinum-
resistant, whereas patients with a PFI greater than a time period of 6 months are regarded as
platinum-sensitive [5]. Recently, BRCA germ-line status, tumor histology, and existence of
hypothetically actionable mutations are additional parameters considered in the selection of
systemic treatment [6,7].
Herein, in this chapter, we review the systemic chemotherapy regimens (mono therapy
and combination therapy) used for the management of patients with recurrent platinum-
sensitive EOC. The rationale is to review the available literature, compare different systemic
chemotherapeutic agents, and provide updated conclusive recommendations. The review will not
include data pertaining to recurrent platinum-resistant EOC. Also, the review will not include the
novel molecularly targeted therapies, such as angiogenesis inhibitors (e.g., bevacizumab), PARP
inhibitors (e.g., rucaparib) and others.
SYSTEMIC CHEMOTHERAPY
Several non-randomized and randomized controlled phase II/III clinical trials have
been conducted to explore the efficacy and safety of mono therapy or combination systemic
chemotherapy for management of patients with recurrent platinum-sensitive EOC.
PLD 109 NR NR NR NR 27
[9] Gordon et al. III 2004
Topotecan 110 NR NR NR NR 17.5
[10] PLD 76 16 43 4 NR 14
Ferrandina et al. III 2008
GEM 77 29 43 5 NR 12.8
Paclitaxel 50 45 21 NR 9 25.8
[13] Cantù et al. I/II 2002
CAP 47 55 30 NR 15.7 34.7
Trabectidine
54 38.9 38.9 6.2 NR NR
(1.5 mg/m2 over 24 hrs) q3w
[17] Del Campo et al. II 2009
Trabectidine
53 35.8 47.2 6.8 NR NR
(1.3 mg/m2 over 3 hrs) q3w
CAP: cyclophosphamide doxorubicin and cisplatin; DS: disease stabilization; GEM: gemcitabine;
HRS: hours; MON: months; N: sample size; NAB-PACLITAXEL: nanoparticle albumin-bound
paclitaxel; NR: not reported; ORR: overall response rate; OS: overall survival; PFS: progression-
free survival; PLD: pegylated liposomal doxorubicin; Q3w: three times per week; Ref: reference;
TTP: time to progression
In 2004, Gordon and colleagues [9] provided a long-term survival data for the earlier above-
mentioned phase III clinical trial [8]. Survival data were mature (87% of patients died, n=413).
For all patients, patients treated with PLD achieved an 18% decrease in the hazard of mortality
(median survival: 62.7 vs. 59.7 weeks, p=0.050) than patients treated with topotecan. For
patients with recurrent platinum-sensitive EOC (n= 219), patients treated with PLD [n=109] had
a statistically significant 30% decrease in the risk of mortality (median survival: 108 vs. 70 weeks,
p=0.017) than patients treated with topotecan [n=110]. There was no survival difference among
patients with recurrent platinum-resistant EOC. The study concluded that PLD yields longer
survival benefits than topotecan in patients with recurrent platinum-sensitive EOC.
In 2008, Ferrandina et al. [10] (phase III clinical trial) randomized 153 patients with recurrent
EOC who experienced relapse within 12 months following completion of an initial platinum-based
chemotherapy. Patients were randomized to receive either GEM (1 g/m2 on days 1, 8, and 15
every 28-day cycle) [n=77] or PLD (40 mg/m2 every 28 days) [n=76]. PLD group achieved a higher
median OS (14 vs. 12.8, p=0.048) than the GEM group. Similarly, PLD group achieved a higher
ORR (29 vs. 16%, p=0.056) than the GEM group. There was no statistically significant difference
in TTP (p=0.411) among both groups. With respect to drug-related side effects, GEM group had
statistically significant rates of grade III/IV neutropenia (p=0.007). On the other hand, PLD group
had higher, although not statistically significant, rates of palmar-plantar erythrodysesthesia (6
vs. 0%, p=0.061) than the GEM group. The study concluded that GEM is not favorable over PLD
in the context of TTP. That being said, GEM may be considered as a potential rescue treatment in
management of patients with recurrent EOC.
In 2008, Katsumata and colleagues [11] (phase II clinical trial by the Japanese Gynecologic
Oncology Group) explored the efficacy of PLD (50 mg/m2) every 28 days in 73 patients with
recurrent EOC. Only 11 patients were platinum-sensitive (16%). Among the platinum-sensitive
patients, only 10 patients were evaluable. The CR, PR, DS and DP occurred in 0, 3, 3 and 4 patients,
respectively. The study concluded that PLD is somehow effective in the platinum-sensitive patient
population. However, additional studies are needed.
Gemcitabine (GEM)
One study was conducted in 2008 by Ferrandina et al. [10]. This study is reported earlier.
Paclitaxel
In 2002, Cantù and partners [13] (phase I/II trial) randomized a total of 97 patients with
recurrent platinum-sensitive EOC to receive either monotherapy paclitaxel (175 mg/m2 IV over 3
hours) or cyclophosphamide, doxorubicin and cisplatin (CAP; 500 mg/m2, 50 mg/m2 and 50 mg/
m2 (CAP) IV, respectively). The paclitaxel group had 50 patients whereas the CAP group had 47
patients; median number of cycles was 6 for both groups. At a median follow up of 49 months,
the CAP group achieved a higher statistically significant median PFI (15.7 vs. 9 months, p=0.038)
and OS (34.7 vs. 25.8 months, p=0.043) than the paclitaxel group. Regarding ORR, the PR and CR
rates in the CAP group were 25 and 30%, respectively. Conversely, the PR and CR rates in the
paclitaxel group were 28 and 17%, respectively (p=0.062). Drug-related adverse events of grade
III/IV leukopenia (34 vs. 4%), grade II/IV neutropenia (36 vs. 13%) and grade II/III nausea/
vomiting (51 vs. 17%) were higher in the CAP group more than the paclitaxel group. On the other
hand, toxicities of allergic reactions (15 vs. 2%) and grade I/II myalgia (19 vs. 4%) were higher in
the paclitaxel group more than the CAP group. The study concluded that mono therapy paclitaxel
is not superior to a platinum-based regimen in patients with recurrent platinum-sensitive EOC.
Large-sized multicenter studies are warranted.
Topotecan
One study was conducted in 2001 by Gordon et al [8]. A follow-up long-term survival data was
conducted in 2004 by Gordon and partners [9]. Both studies are reported earlier.
In 2008, Morris et al [19] (phase II clinical trial) explored the efficacy and safety of topotecan
(4 mg/m2 weekly as tolerated until disease progression) in 41 patients with recurrent platinum-
sensitive EOC. A median of 9 topotecan cycles were administrated and ranged from as low as 1
to as high as 45 cycles. Overall, the drug schedule was well-endured; there were no incidences
of grade IV anemia or thrombocytopenia. However, around 9 (22%) and 7 (17%) patients
developed grade III/IV fatigue and neutropenia, respectively. There was a total of 38 patients
who were assessable for drug-related response. A sum of 1, 8, 13, and 16 patients developed CR
(3%), PR (21%), DP (34%), and DS (42%), respectively. The study concluded that weekly dosing
of topotecan was efficacious, well-endured, and yield analogous outcomes to that of the classical
5-day regimen.
Iproplatin
In 1991, Weiss and colleagues [20] explored the role of iproplatin (initial dose: 270 mg/m2,
range: 135-340 mg/m2 as per toxicity) as a second-line salvage therapy in 105 patients with
recurrent platinum-sensitive and platinum-resistant EOC. There were 101 patients who had
measurable disease. The DOR ranged from 2 to 20 months.In patients who were resistant to
carboplatin, the ORR was 12% (total=2/18, PR=2, CR=0) whereas in patients who were resistant
to cisplatin, the ORR was 12% (total=7/60, PR=4, CR= 3). Most importantly, in platinum-sensitive
patients treated with cisplatin, the ORR was 26% (total=5/19, PR=2, CR= 3). The most frequently
reported side effects (in an ascending order) were diarrhea (40%), anemia (68%), leukopenia
(76%) and thrombocytopenia (93%). The study concluded that iproplatin is not advised as
therapeutic second-line chemotherapy in patients with platinum-sensitive as well as platinum-
resistant EOC (due to cross-reactivity with platinum-based agents, namely carboplatin and
cisplatin).
[29] Ferrero et al. II 2007 Carboplatin plus PLD 104 63 19.2 NR 9.4 32
II
[30] Weber et al. 2009 Carboplatin plus PLD 81 65.4 22.2 NR 13.6 38.9
[34] Zanaboni et al. II/III 1991 Cisplatin plus epirubicin or etoposide 40 60 NR NR NR 13.5
DS: disease stabilization; MON: months; N: sample size; NR: not reported; ORR: overall
response rate; OS: overall survival; PFS: progression-free survival; PLD: pegylated liposomal
doxorubicin; REF: reference; TTP: time to progression.
In 2005, Rose et al. [23] (phase II clinical trial) examined the role of paclitaxel (80 mg/m2
over 1 hour infusion on days 1, 8 and 15) plus carboplatin (AUC of 5 on day 1 only) in 28 patients
with recurrent platinum-sensitive EOC. A median of 6 courses was administered and ranged
from as low as 1 to as high as 13 cycles. Paclitaxel dose decreased to 60 mg/m2 were deemed
necessary in around 85% of patients. Grade III thrombocytopenia, grade III neutropenia, grade IV
thrombocytopenia, grade IV neutropenia and neutropenic fever were observed in 5, 14, 0, 1 and 1
patients, respectively. Around 77% of the evaluable patients (n=20/26) demonstrated response
to treatment, of which 15 and 5 patients exhibited CR and PR, respectively. The study concluded
that a regimen of weekly paclitaxel (60mg/m2) plus carboplatin (AUC of 5) is largely endured and
therapeutic in patients with recurrent platinum-sensitive EOC.
Ovarian Cancer | www.smgebooks.com 9
Copyright Abu-Zaid A.This book chapter is open access distributed under the Creative Commons Attribution 4.0
International License, which allows users to download, copy and build upon published articles even for commercial
purposes, as long as the author and publisher are properly credited.
In 2009, Hoekstra and associates [24] performed a retrospective chart review exploring the
role of weekly paclitaxel (80 mg/m2 on days 1, 8, 15) and monthly carboplatin (AUC 5 on day
1) of a 28-day cycle in 20 patients with recurrent EOC. A total of 15 patients were regarded as
platinum-sensitive whereas 5 patients were regarded as platinum-resistant. For all patients, the
ORR was 85% (n=17/20), as follows: PR (12%, n=2/17) and CR (78%, n=15/17). Specifically,
in platinum-sensitive patients, the ORR was 94% (n=14/15). Even after a median follow up of
2 years and 4 months, median survival could not be documented. Only 35% of patients (n=7)
exhibited neutropenia of grade III-IV drug-related adverse events. Moreover, 25% of patients
displayed platinum hypersensitivity; however, they progressed with successful treatment
through administration of a carboplatin desensitization procedure. The study concluded that a
regimen of weekly paclitaxel plus monthly carboplatin is effective and potentially safe in patients
with recurrent platinum-sensitive EOC. Large-sized multicenter study is warranted.
In 2010, Bafaloukos and colleagues [25] (phase II clinical trial, Hellenic Cooperative Oncology
Group study) randomized 189 patients with recurrent platinum-sensitive EOC to receive either
PLD (45 mg/m2 once every 28 days) plus carboplatin (AUC of 5) [Group A, n=93] or paclitaxel
(175 mg/m2 once every 21 days) plus carboplatin (AUC of 5) [Group B, n=96]. There were no
statistically significant differences between both groups regarding ORR (51 vs 58%), CR rate (23
vs. 34%), median OS (24.7 vs. 29.4 months), and median TTP (11.8 vs. 10.8 months). Although
there was no drug-related fatality reported, termination of treatment was statistically significantly
higher in Group B than Group A (13.5 vs. 3%, p=0.016). For both groups, neutropenia was the
most frequently documented side effect (Group A vs. Group B: 35 vs. 30%). Group A had higher
statistically significant rates of the following side effects than group B: severe thrombocytopenia
(11 vs. 2%, p=0.016) and grade II palmar-plantar erythrodysesthesia (38 vs. 9%, p<0.001).
Conversely, Group B had higher statistically significant rates of the following side effects than
group A: grade III neurotoxicity (7 vs. 0%, p=0.029) and grade III alopecia (20 vs. 5%, p=0.003).
The study concluded that PLD plus carboplatin is an active treatment in patients with recurrent
platinum-sensitive EOC with low associated frequencies of alopecia and neurotoxicity side
effects. A phase III clinical trial is deemed necessary to further assess the efficacy and safety of the
combination regimen.
In 2011, Joly et al. [27] monitored the rate of hypersensitivity reactions (HSRs) in the above-
mentioned CALYPSO phase III clinical trial [26]. Data available for 466 and 502 patients in Group
A and Group B, respectively. It was noted that Group A had a higher rate of HSRs than Group B
within the first chemotherapeutic schedule (46 vs. 16%). However, overall, Group B experienced a
higher statistically significant rate of HSRs than group A (33.1 vs. 15.5%, p<0.001). Chemotherapy
regimen and age were sub-analyzed as multivariate predictors of allergy. At the conclusion of the
study, it was reported that the combination PLD plus carboplatin as well as older age ≥ 70 years
old were associated with a low frequency of HSRs in patients with recurrent platinum-sensitive
EOC.
In 2012, Wagner et al. [28] released the final OS analysis of the CALYPSO phase III clinical
trial [26]. The median follow-up was 49 months. There was no statistically significant difference
of OS between Group A and Group B (30.7 vs. 33 months, p=0.94). The study concluded that PLD
plus carboplatin is associated with postponed disease progression and equivalent OS outcomes to
paclitaxel plus carboplatin regimen in patients with recurrent platinum-sensitive EOC.
In 2009, Weber and colleagues [30] (prospective GINECO phase II clinical trial) administered
carboplatin (AUF of 5) plus PLD (30 mg/m2) every 4 weeks for a maximum of 6 cycles of occurrence
of disease progression, in 81 patients with recurrent platinum-sensitive EOC. The median PFS, OS
and ORR were 13.6 months, 38.9 months and 65.4%, respectively. Hematological drug-related
adverse events were more frequently reported than non-hematological ones. Neither drug-
related fatality nor cardiotoxicity were observed. The study concluded that carboplatin plus PLD
is an active treatment and well-endured in patients with recurrent platinum-sensitive EOC.
In 2010, a study was conducted by Bafaloukos and colleagues [25]. This study is reported
earlier.
In 2011, a study was conducted by Joly et al. [27]. This study is reported earlier.
In 2012, a study was conducted by Wagner et al. [28]. This study is reported earlier.
In 2011, Poveda and colleagues [36] (OVA-301 phase III clinical trial) reported the outcomes
of the OVA-301 study [35] for the 214 patients with platinum-sensitive EOC. The trabectidine plus
In 2012, Monk and partners [37] reported the OS analysis of OVA-301 phase III clinical trial [35].
The study was powered to demonstrate a 33% increase in the OS after 520 deaths occurred. The
median follow-up was approximately 47.5 months. The trabectidine plus PLD group had a higher
statistically significant median OS (p=0.0285) than the single-agent PLD group; the platinum-
sensitive group had the most pronounced advantage of OS as opposed to the platinum-resistant
group (p=0.0027). The analysis included several unexpected outcomes and further secondary
analyses/hypotheses were generated. At the conclusion of the study, it was determined that the
final analysis of OS did not match the protocol-defined condition for statistical significance, and
the PFI influenced the OS, rendering the interpretation of results uncertain.
CONCLUSIONS
• Epithelial ovarian cancer (EOC) remains a principal cause of cancer-related mortality in
women.
• Combination novel molecularly targeted therapy and systemic chemotherapy is an active and
exciting area for research.
References
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015; 65: 5-29.
2. Foley OW, Rauh-Hain JA, Del Carmen MG. Recurrent epithelial ovarian cancer: an update on treatment. Oncology (Williston Park).
2013; 27: 288-294.
3. Wu YS, Shui L, Shen D, Chen X. Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and
meta-analysis of randomized controlled trials. Oncotarget. 2017; 8: 10703-10713.
4. González Martín A, Bratos R, Márquez R, Alonso S, Chiva L. Bevacizumab as front-line treatment for newly diagnosed epithelial
cancer. Expert Rev Anticancer Ther. 2013; 13: 123-129.
5. Teplinsky E, Herzog TJ. The efficacy of trabectedin in treating ovarian cancer. Expert Opin Pharmacother. 2017; 18: 313-323.
6. Alvarez RD, Karlan BY, Strauss JF. “Ovarian cancers: Evolving paradigms in research and care”: Report from the Institute of
Medicine. Gynecol Oncol. 2016; 141: 413-415.
7. Alvarez RD, Matulonis UA, Herzog TJ, Coleman RL, Monk BJ, et al. Moving beyond the platinum sensitive/resistant paradigm for
patients with recurrent ovarian cancer. Gynecol Oncol. 2016; 141: 405-409.
9. Gordon AN, Tonda M, Sun S, Rackoff W. Investigators, Long-term survival advantage for women treated with pegylated liposomal
doxorubicin compared with topotecan in a phase 3 randomized study of recurr. Gynecol Oncol. 2004; 95: 1-8.
10. Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, et al. Phase III trial of gemcitabine compared with pegylated liposomal
doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008; 26: 890-896.
11. Katsumata N, Fujiwara Y, Kamura T, Nakanishi T, Hatae M, et al. Phase II clinical trial of pegylated liposomal doxorubicin (JNS002)
in Japanese patients with mullerian carcinoma (epithelial ovarian carcinoma, primary carcinoma of fallopian tube, peritoneal
carcinoma) having a therapeutic history of platinum-based chemotherapy: a Phase II Study of the Japanese Gynecologic Oncology
Group. Jpn J Clin Oncol. 2008; 38: 777-785.
12. Rose PG, Blessing JA, Mayer AR, Homesley HD. Prolonged oral etoposide as second-line therapy for platinum-resistant and
platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998; 16: 405-410.
13. Cantù MG, Buda A, Parma G, Rossi R, Floriani I, et al. Randomized controlled trial of single-agent paclitaxel versus
cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer. 2002; 20: 1232-1237.
14. Teneriello MG, Tseng PC, Crozier M, Encarnacion C, Hancock K, et al. Phase II evaluation of nanoparticle albumin-bound paclitaxel
in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer. J Clin Oncol. 2009; 27: 1426-1431.
15. Sessa C, De Braud F, Perotti A, Bauer J, Curigliano G, et al. Trabectedin for women with ovarian carcinoma after treatment with
platinum and taxanes fails. J Clin Oncol. 2005; 23: 1867-1874.
16. Krasner CN, McMeekin DS, Chan S, Braly PS, Renshaw FG, et al. A Phase II study of trabectedin single agent in patients with
recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer. 2007; 97: 1618-1624.
17. Del Campo JM, Roszak A, Bidzinski M, Ciuleanu TE, Hogberg T, et al. Phase II randomized study of trabectedin given as two
different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced
ovarian cancer. Ann Oncol. 2009; 20: 1794-1802.
18. del Campo JM, Sessa C, Krasner CN, Vermorken JB, Colombo N, et al. Trabectedin as single agent in relapsed advanced ovarian
cancer: results from a retrospective pooled analysis of three phase II trials. Med Oncol. 2013; 30: 435.
19. Morris R, Alvarez R, Andrews S, Malone J, Bryant C, et al. Topotecan weekly bolus chemotherapy for relapsed platinum-sensitive
ovarian and peritoneal cancers. Gynecol Oncol, 2008; 109: 10.1016.
20. Weiss G, Green S, Alberts DS, Thigpen JT, Hines HE, et al. Second-line treatment of advanced measurable ovarian cancer with
iproplatin: a Southwest Oncology Group study. Eur J Cancer. 1991; 27: 135-138.
21. Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, et al. Paclitaxel plus platinum-based chemotherapy versus
conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet.
2003; 361: 2099-2106.
22. Rose PG, Fusco N, Fluellen L, Rodriguez M. Second-line therapy with paclitaxel and carboplatin for recurrent disease following
first-line therapy with paclitaxel and platinum in ovarian or peritoneal carcinoma. J Clin Oncol. 1998; 16: 1494-1497.
23. Rose PG, Smrekar M, Fusco N. A phase II trial of weekly paclitaxel and every 3 weeks of carboplatin in potentially platinum-
sensitive ovarian and peritoneal carcinoma. Gynecol Oncol. 2005; 96: 296-300.
24. Hoekstra AV, Hurteau JA, Kirschner CV, Rodriguez GC. The combination of monthly carboplatin and weekly paclitaxel is highly
active for the treatment of recurrent ovarian cancer. Gynecol Oncol. 2009; 115: 377-381.
25. Bafaloukos D, Linardou H, Aravantinos G, Papadimitriou C, Bamias A, et al. A randomized phase II study of carboplatin plus
pegylated liposomal doxorubicin versus carboplatin plus paclitaxel in platinum sensitive ovarian cancer. 2010; 8: 3.
26. Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, et al. Pegylated liposomal Doxorubicin and Carboplatin
compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010;
28: 3323-3329.
27. Joly F, Ray-Coquard I, Fabbro M, Donoghoe M, Boman K, et al. Decreased hypersensitivity reactions with carboplatin-pegylated
liposomal doxorubicin compared to carboplatin-paclitaxel combination: analysis from the GCIG CALYPSO relapsing ovarian
cancer trial. Gynecol Oncol. 2011; 122: 226-232.
28. Wagner U, Marth, C, Largillier R, Kaern J, Brown C, et al. Final overall survival results of phase III GCIG CALYPSO trial of
pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J
Cancer. 2012; 107: 588-591.
30. Weber B, Lortholary A, Mayer F, Bourgeois H, Orfeuvre H, et al. Pegylated liposomal doxorubicin and carboplatin in late-relapsing
ovarian cancer: a GINECO group phase II trial. Anticancer Res. 2009; 29: 4195-4200.
31. Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, et al. Gemcitabine plus carboplatin compared with carboplatin in patients with
platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin
Oncol. 2006; 24: 4699-4707.
32. Bolis G, Scarfone G, Giardina G, Villa A, Mangili G, et al. Carboplatin alone vs carboplatin plus epidoxorubicin as second-line
therapy for cisplatin- or carboplatin-sensitive ovarian cancer. Gynecol Oncol. 2001; 81: 3-9.
33. van der Burg ME, Hoff AM, van Lent M, Rodenburg CJ, van Putten WL, et al. Carboplatin and cyclophosphamide salvage therapy
for ovarian cancer patients relapsing after cisplatin combination chemotherapy. Eur J Cance. 1991; 27: 248-250.
34. Zanaboni F, Scarfone G, Presti M, Maggi R, Borello C, et al. Salvage chemotherapy for ovarian cancer recurrence: weekly cisplatin
in combination with epirubicin or etoposide. Gynecol Oncol. 1991; 43: 24-28.
35. Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, et al. Trabectedin plus pegylated liposomal Doxorubicin in recurrent
ovarian cancer. J Clin Oncol. 2010; 28: 3107-3114.
36. Poveda A, Vergote I, Tjulandin S, Kong B, Roy M, et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian
cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III
randomized trial. Ann Oncol. 2011; 22: 39-48.
37. Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, et al. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus
PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012; 48: 2361-2368.
38. Joly F, Petit T, Pautier P, Guardiola E, Mayer F, et al. Weekly combination of topotecan and gemcitabine in early recurrent ovarian
cancer patients: a French multicenter phase II study. Gynecol Oncol. 2009; 115: 382-388.