Topotecan Use for Second-Line Treatment in Patients with Recurrent or Metastatic
Cervical Cancer at Brazilian National Cancer Institute (INCA)
1098
The median PFS for the entire group was 2.93 months
(95% CI 2.41 - 3.45) and OS was 4.66 months (95% CI
1.21 - 8.11).
4. Discussion
The combination of paclitaxel and cisplatin (or carbo-
platin alternatively) is a worldwide current first choice
for systemic treatment in advanced and persistent/recur-
rent cervical cancer not amenable to curative therapy
with an overall response rate of 36% [9]. Patients who
have progressed after platinum-based therapy may be
treated with second-line schemas, included in clinical
studies or receive best supportive care measures.
A variety of second-line agents have been tested in this
scenario [10-12] and the efficacy is rather modest. Topo-
tecan is one of the cytotoxic options that had been inves-
tigated for antineoplastic activity in a small number of
trials. The heterogeneity of patients accrued in these
studies render it impossible to compare results among
them. It seems that topotecan, as a single agent or in
combination, exihibits only modest activity in a popula-
tion of previously treated patients with cervical cancer
albeit at a cost of substantial hematologic toxicity [11].
There is clearly an unmet need for active new thera-
pies in the management of advanced cervical cancer. The
poor outcome for these patients warrants the develop-
ment of novel therapeutic strategies that exploit abnormal
tumor biology.
Some targeted drugs modulating different signal trans-
duction pathways are currently under clinical develop-
ment inhibiting angiogenesis, targeting epidermal gro wth
factor receptor (EGFR), cell cycle, matrix metallopro-
teinases, cyclooxygenase-2, mammalian target of rapa-
mycin (mTOR) or proteasome, evaluating efficacy and
safety [11-13]. However, no phase III trials have been
published and consequently no molecularly targeted agents
have been approved for use in clinical practice.
The limited activity of topotecan schemas in second-
line treatment of cervical cancer and the associated over-
all toxicity as shown in this retrospective study may not
justify their use in this settin g. Patients who progress after
first-line treatment may be offered participation in clini-
cal trials, other second-line agents or best supportive care
measures.
REFERENCES
[1] J. Ferlay, H. R. Shin, F. Bray , D. Forman, C. Mathers and
D. M. Parkinm “GLOBOCAN 2008 v2.0, Cancer Inci-
dence and Mortality Worldwide: IARC Cancer Base No.
10,” International Agency for Research on Cancer, Lyon,
2010. http://globocan.iarc.fr
[2] J. Coronel, L. Cetina, M. Candelaria, A. González-Fierro,
D. Arias, D. Cantu, et al., “Weekly Topotecan as Second-
or Third-Line Treatment in Patients with Recurrent or
Metastatic Cervical Cancer,” Medical Oncology, Vol. 26,
No. 2, 2009, pp. 210-214.
doi:10.1007/s12032-008-9108-5
[3] L. A. G. Ries, M. P. Eisner, C. L. Kosary, B. F. Hankey,
B. A. Miller, L. Clegg, et al., “SEER Cancer Statistics
Review, 1973-1998,” National Cancer Institute, Bethesda,
2012.
http://seer.cancer.gov/Publications/CSR1973_1998/2001
[4] J. V. Fiorica, J. A. Blessing, L. V. Puneky , A. A. Se cord,
J. S. Hoffman, S. D. Yamada, et al., “A Phase II Evalua-
tion of Weekly Topotecan as a Single Agent Second Line
Therapy in Persistent or Recurrent Carcinoma of the Cer-
vix: A Gynecologic Oncology Group Study,” Gyneco-
logic Oncology, Vol. 115, No. 2, 2009, pp. 285-289.
doi:10.1016/j.ygyno.2009.07.024
[5] P. Boabang, C. M. Kurbacher, H. Kohlhagen, A. Waida
and B. K. Amo-Takyi, “Anti-Neoplastic Activity of Topo-
tecan versus Cisplatin, Etoposide and Paclitaxel in Four
Squamous Cell Cancer Cell Lines of the Female Genital
Tract Using an ATP-Tumor Chemosensitivity Assay ,” An-
ticancer Drugs, Vol. 11, No. 10, 2000, pp. 843-848.
[6] K. Noda, H. Sasaki, K. Yamamoto, T. Yamamoto, R.
Nishimura, T. Sugiyama, et al., “Phase II Trial of Topo-
tecan for Cervical Cancer of the Uterus,” Proceedings of
the American Society of Clinical Oncologists, Vol. 15,
1996, p. 754.
[7] M. A. Bookman, J. A. Blessing, P. Hanjani, T. J. Herzog
and W. A. Andersen, “Topotecan in Squamous Cell Car-
cinoma of the Cervix: A Phase II Study of the Gyneco-
logic Oncology Group,” Gynecologic Oncology, Vol. 77,
No. 3, 2000, pp. 446-449. doi:10.1006/gyno.2000.5807
[8] N. R. Abu-Rustum, S. Lee and L. S. Massad, “Topotecan
for Recurrent Cervical Cancer after Platinum-Based Ther-
apy,” International Journal of Gynecological Cancer,
Vol. 10, No. 4, 2000, pp. 285-288.
doi:10.1046/j.1525-1438.2000.010004285.x
[9] D. H. Moore, J. A. Blessing, R. P. McQuellon, H. T.
Thaler, D. Cella, J. Benda, et al., “Phase III Study of Cis-
platin with or without Paclitaxel in Stage IVB, Recurrent,
or Persistent Squamous Cell Carcinoma of the Cervix: A
Gynecologic Oncology Group Study,” Journal of Clinical
Oncology, Vol. 22, No. 15, 2004, pp. 3113-3119.
[10] H. J. Long III., “Management of Metastatic Cervical Can-
cer: Review of the Literature,” Journal of Clinical On-
cology, Vol. 25, No. 20, 2007, pp. 2966-2974.
[11] F. Zagouri, T. N. Sergentanis, D. Chrysikos, M. Filipits
and R. Bartsch, “Molecularly Targeted Therapies in Cer-
vical Cancer. A Systematic Review,” Gynecologic Onco-
logy, Vol. 126, No. 2, 2012, pp. 291-303.
doi:10.1016/j.ygyno.2012.04.007
[12] B. J. Monk, M. W. Sill, R. A. Burger, H. J. Gray, T. E.
Buekers and L. D. Roman, “Phase II Trial of Bevacizu-
mab in the Treatment of Persistent or Recurrent Squa-
mous Cell Carcinoma of the Cervix: A Gynecologic On-
cology Group Study,” Journal of Clinical Oncology, Vol.
27, No. 7, 2009, pp. 1069-1074.
doi:10.1200/JCO.2008.18.9043
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