Taiwanese Journal of Obstetrics & Gynecology 61 (2022) 573e574

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Taiwanese Journal of Obstetrics & Gynecology

Editorial

Chemotherapy adjuvant and chemotherapy-induced neutropenia

Chemotherapy may be one of the most frequently used tools for course in Dr. Tojima's study [13]. Additionally, 87% of patients did
the treatment of various kinds of gynecologic cancers, applied develop grade 4 neutropenia in their study [13]. All suggested that
either before the definite treatment or during or post the definite the doxorubicin-cisplatin is very strong myelosuppressive regimen,
treatment as well as used as purpose for a rescue or palliative treat- which raised the following question whether the doxorubicin-
ment, although many issues should be considered [1e4]. Among cisplatin regimen is a better choice as the first-line chemotherapy
these, chemotherapy-related adverse events (AEs) and/or side ef- for treatment of patients with uterine cancer or not. Although the
fects (SEs) are a critical factor, partly because of their occurrence answer may be debated, our response is “not”. The reasons are
in much frequency and partly because of the involvement of delay- shown below. The paclitaxel-carboplatin (CP) has been well accepted
ing the time of application on schedule and/or reducing therapeutic as the regimen of the therapeutic choice in the management of
dose as well as causing much bothersome problems of the patients women with uterine cancer who should be treated with chemo-
to deteriorate life of quality and face the life-threatening complica- therapy [2,7,14,15]. We are wondering why the authors use
tions [5e8]. Chemotherapy-related myelosuppression, especially doxorubicin-cisplatin in place of CP for their patients. As shown by
chemotherapy-induced neutropenia (CIN) may be one of the author [13], doxorubicin-cisplatin is associated not only with high
most frequently occurred AEs and/or SEs. Although many strategies hematologic, neurologic and cardiac toxicity, but also with higher
have been proposed to ameliorate the occurrence of CIN, such as costs, which required G-CSF support or cumbersome delayed treat-
the use of weekly dose dense paclitaxel and triweekly low-dose ment, reduced dose and potential risks of this regimen-associated
cisplatin regimen in place of the original conventional triweekly AEs and/or SEs to prolong hospitalization, hinting the development
paclitaxel and carboplatin or conventional dose-dense paclitaxel of new protocol is urgently needed, since the better regimen should
and triweekly carboplatin, there is no doubt that CIN cannot be take the following benefits, such as convenience, less myelosuppres-
totally avoided [9e11]. CIN, the decrease of immune cells (white sion, a better cost profile and less toxicity. In our previous study
blood cells), not only decreases the ability of host against the infec- enrolling 541 patients with the pathologically-confirmed Interna-
tion by micro-organisms but also impairs the tumor clearance tional Federation of Gynaecology and Obstetrics (FIGO) III-IV pure
[9e12]. All may compromise treatment efficacy and even result in endometrioid type endometrial cancer from 22-member hospitals,
patients’ death [9e12]. In a publication of the March issue of Taiwa- we found that combination of complete staging surgery, including
nese Journal of Obstetrics and Gynecology (TJOG), we are happy to complete dissection of para-aortic lymph nodes and pelvic lymph
learn the researchers who would like to focus this topic to improve nodes and the following CP therapy could provide the better chance
the cancer treatment for patients with gynecological cancer [13]. to survive with hazard ratio (HR) of 0.27 (95% confidence interval [CI]
Dr. Tojima and colleagues using a long-acting granulocyte colony- 0.16e0.45) and 0.14 (95% CI 0.08e0.26) for progression-free survival
stimulating factor (GeCSF)e-pegfilgrastim as a prophylaxis for (PFS) and HR of 0.61 (95% CI 0.79e0.92), and 0.48 (95% CI 0.31e0.75)
chemotherapy-induced neutropenia in endometrial cancer pa- for overall survival (OS), suggesting that CP regimen should be
tients attempted to evaluate the effect of this strategy [13]. considered as the first-line adjuvant chemotherapy for women
This retrospective study enrolling a total of 48 women with with endometrial cancer, who need the further chemotherapy [14].
endometrial cancer who were treated with postoperative adjuvant Furthermore, a recent phase III randomized trial (protocol GOG-
chemotherapy by doxorubicin plus cisplatin [13]. Among these pa- 0261) evaluating the standard regimen for the therapy of women
tients, 23 women did not receive prophylactic pegfilgrastim with uterine carcinosarcoma (UCS), which is one of the subtype of
compared to 25 women did [13]. The results of the study showed uterine carcinomas concluded that CP regimen for UCS is a path to
that patients treated with prophylactic pegfilgrastim had a statisti- conclusion [16,17]. The study compared the standard CP regimen
cally significantly lower rate of febrile neutropenia (FN) and grade 4 typically used to treat epithelial gynecologic tumors with ifosfa-
neutropenia than those without (8.0% versus 34.8% and 12% versus mide/paclitaxel, a combination developed specifically for sarcomas,
87%, respectively), suggesting that the use of prophylactic pegfil- and the results showed the CP regimen presented a favor trend to
grastim effectively prevented FN in patients treated with doxoru- ifosfamide/paclitaxel regimen with the median OS of 37 versus 29
bicin plus cisplatin (doxorubicin-cisplatin) [13]. The Tojima's months, respectively (HR 0.87, 90% CI 0.70e1.075) [17]. Furthermore,
study is interesting and valuable and worthy of further discussion. CP led to significantly improved PFS (16 months versus 12 months
First, it is well-known that guidelines have recommended the use with HR of 0.735, 95% CI 0.58e0.93) for patients with UCS [17]. More-
of G-CSF as primary prophylaxis during chemotherapy if the risk of over, patients treated with ifosfamide/paclitaxel were more likely to
CIN is greater than 20% [8]. In fact, we found that 10 patients of 58 experience confusion and grade 3 neurologic toxicity, and all-grade
patients (near 20% of patients) had reduced doses from the first renal toxicity and genitourinary hemorrhage were also more

https://doi.org/10.1016/j.tjog.2022.05.001
1028-4559/© 2022 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
Y.-T. Li, S.-T. Yang and P.-H. Wang Taiwanese Journal of Obstetrics & Gynecology 61 (2022) 573e574

frequent with ifosfamide/paclitaxel than with CP, although grade 3 [3] Liu CH, Kung YH, Chien-Fu Lin J, Chuang CM, Wu HH, Jiang LY, et al. Synergistic
therapeutic effect of low-dose bevacizumab with cisplatin-based chemotherapy
hematologic toxicity was more apparent in the CP group, in the
for advanced or recurrent cervical cancer. J Chin Med Assoc 2021;84:1139e44.
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associated with significant clinical complication [17]. All support Taiwan J Obstet Gynecol 2022;61:3e4.
that CP, the less toxic regimen with a comparable level or a trend [5] Lee WL, Chang WH, Wang PH. Fever during chemotherapy: hypersensitivity
reactions. Taiwan J Obstet Gynecol 2021;60:977e8.
of favoring level of therapeutic effect, should become the preferred [6] Lee WL, Chang WH, Wang PH. Gastrointestinal perforations in a patient
regimen for upfront treatment of UCS [17]. Therefore, going forward, treated by Bevacizumab and chemotherapy: is it an anaphylactic reaction?
we don't think that doxorubicin-cisplatin regimen should be consid- Taiwan J Obstet Gynecol 2020;59:629e30.
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Second, it is very interesting to find that the use of prophylactic phylactic pegfilgrastim to prevent febrile neutropenia among patients
receiving biweekly (Q2W) chemotherapy regimens: a systematic review of ef-
pegfilgrastim also decreases the rate of anemia and thrombocyto- ficacy, effectiveness and safety. BMC Cancer 2021;21:621.
penia in their study. Originally, pegfilgrastim, a long-acting G-CSF, [9] Cheng M, Lee HH, Chang WH, Lee NR, Huang HY, Chen YJ, et al. Weekly dose-
is indicated to decrease the risk of infection manifested by CIN dense paclitaxel and triweekly low-dose cisplatin: a well-tolerated and effec-
tive chemotherapeutic regimen for first-line treatment of advanced ovarian,
and shorten the duration of CIN, and it can be applied once per cy- Fallopian tube, and primary peritoneal cancer. Int J Environ Res Publ Health
cle, and its use based on the recommendation by the USA Food and 2019;16:4794.
Drug Administration (FDA)should not be administered 14 days [10] Huang CY, Chang CM, Wang PH. Dose-dense chemotherapy: a possible high
cost-effectiveness treatment for ovarian cancer. Taiwan J Obstet Gynecol
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2020;59:351e2.
which is based on the rationale for avoiding concurrent (same [11] Huang CY, Cheng M, Lee NR, Huang HY, Lee WL, Chang WH, et al. Comparing
day as last chemotherapy dose) administration of G-CSF and paclitaxel-carboplatin with paclitaxel-cisplatin as the front-line chemo-
chemotherapy is that stimulation of bone marrow progenitors by therapy for patients with FIGO IIIC serous-type tubo-ovarian cancer. Int J En-
viron Res Publ Health 2020;17:2213.
the G-CSF increases the pool of precursor myeloid cells susceptible [12] Lee WL, Wang PH. Immunology and ovarian cancers. J Chin Med Assoc
to destruction by the myelosuppressive agents [8]. Recently, the 2020;83:425e32.
National Comprehensive Cancer Network (NCCN) and the European [13] Tojima Y, Taguchi A, More M, Nara K, Miyamoto Y, Tanikawa M, et al. Effect of
primary prophylaxis with pegfilgrastim in endometrial cancer patients treated
Organization for Research and Treatment of Cancer (EORTC) guide- with doxorubicin and cisplatin. Taiwan J Obstet Gynecol 2022;61:265e9.
lines suggest that at least 12 days between a dose of pegfilgrastim [14] Chen JR, Chang TC, Fu HC, Lau HY, Chen IH, Ke YM, et al. Outcomes of patients
and the next cycle of chemotherapy [8]. However, the suggestion with surgically and pathologically staged IIIA-IVB pure endometrioid-type
endometrial cancer: a Taiwanese Gynecology Oncology Group (TGOG-2005)
for the treatment of cancer-related anemia and/or myelosuppres- retrospective cohort study (A STROBE-Compliant Article). Medicine (Baltim)
sive chemotherapy-related anemia includes erythropoiesis- 2016;95:e3330.
stimulating agents (ESAs), red blood cell transfusion or intravenous [15] Yang ST, Wang PH. Abandon ifosfamide-based regimen and use paclitaxel-
carboplatin regimen for the treatment of uterine carcinosarcoma. J Chin
(IV) or oral iron replacement [18]. Oral iron includes three products: Med Assoc 2022;85:649e50.
low-molecular iron dextran, ferric gluconate and iron sucrose ac- [16] Roque DR, Matei D. Paclitaxel and carboplatin for uterine carcinosarcoma: a
cording to the advantages, such as less controversies, lower in path to inclusion. J Clin Oncol 2022;40:924e6.
[17] Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, et al. Ran-
cost, not mandating a particular hemoglobin target for initiating
domized phase III trial of paclitaxel and carboplatin versus paclitaxel and ifos-
or withholding IV iron [18]. Therefore, the finding about the famide in patients with carcinosarcoma of the uterus or ovary: an NRG
decreased rate of anemia and thrombocytopenia in patients with oncology trial. J Clin Oncol 2022;40:968e77.
prophylactic pegfilgrastim needs a further validation. [18] Crawford J, Rodgers GM. Treatment strategies for myeloid growth factors and
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Taken together, based on the findings from Dr. Tojima's study Suppl):821e4.
and recent evidence, the choice of chemotherapy regimen for
women with endometrial cancer should follow the general princi-
Yiu-Tai Li
ple as less toxicity and no compromising therapeutic effect. There-
Department of Obstetrics and Gynecology, Kuo General Hospital,
fore, doxorubicin-cisplatin regimen is not recommended to be used
Tainan, Taiwan
as the front-line therapy for women with endometrial cancer who
need chemotherapy. Szu-Ting Yang
Institute of Clinical Medicine, National Yang Ming Chiao Tung
Conflicts of interest University, Taipei, Taiwan
Department of Obstetrics and Gynecology, Taipei Veterans General
All authors declare no conflict of interest.
Hospital, Taipei, Taiwan
Acknowledgements Peng-Hui Wang*
Institute of Clinical Medicine, National Yang Ming Chiao Tung
This research was supported by grants from the Taipei Veterans University, Taipei, Taiwan
General Hospital (V110C-082; V111C-103; and V111A-009) and the
Department of Obstetrics and Gynecology, Taipei Veterans General
Ministry of Science and Technology, Executive Yuan (MOST: 110-
Hospital, Taipei, Taiwan
2314-B-075-016 MY3), Taipei, Taiwan. The authors appreciate the
support from Female Cancer Foundation, Taipei, Taiwan. Female Cancer Foundation, Taipei, Taiwan
Department of Medical Research, China Medical University Hospital,
References Taichung, Taiwan

[1] Yang ST, Chang WH, Lee NR, Lai WA, Shen SH, Lee WL, et al. Endometriosis- *
associated epithelial ovarian cancer is a more complicated disease than we Corresponding author. Department of Obstetrics and Gynecology,
suspected before. Taiwan J Obstet Gynecol 2021;60:1112e5. Taipei Veterans General Hospital, 201 Section 2, Shih-Pai Road,
[2] Su MH, Wu HH, Huang HY, Lee NR, Chang WH, Lin SC, et al. Comparing Taipei 11217, Taiwan.
paclitaxel-platinum with ifosfamide-platinum as the front-line chemotherapy
for patients with advanced-stage uterine carcinosarcoma. J Chin Med Assoc E-mail addresses: [email protected],
2022;85:204e11. [email protected] (P.-H. Wang).

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