Dose-dense Paclitaxel- and Carboplatin-based Neoadjuvant Chemotherapy Followed by Surgery or Concurrent Chemoradiotherapy in Cervical Cancer: a Preliminary Analysis

Gadducci, Angiolo; Barsotti, Cecilia; Laliscia, Concetta; Cosio, Stefania; Fanucchi, A; Tana, Roberta; Fabrini, Maria Grazia

doi:10.21873/anticanres.11441

Cited by 18 publications

(8 citation statements)

References 37 publications

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“…In our early experience, dose-dense chemotherapy obtained an overall response and optimal pathological response in 14 (82.3%) and in 3 (17.6%) of 17 patients, respectively (69). Histologically positive nodes, positive parametria and positive surgical margins were found in 12.5%, 18.7% and 6.2%, respectively, of the 16 patients who underwent radical hysterectomy.…”

Section: Neoadjuvant Chemotherapy Followed By Radical Surgerymentioning

confidence: 82%

Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: Review of the Literature and Perspectives of Clinical Research

Gadducci

Cosio

2020

Anticancer Res

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Concurrent cisplatin-based chemotherapy and radiotherapy (CCRT) plus brachytherapy is standard treatment for locally advanced cervical cancer. Platinumbased neoadjuvant chemotherapy (NACT) followed by radical hysterectomy has been proposed as an alternative approach, especially for patients with stage Ib2-IIb disease. This review analyzes the most commonly used combination regimens in this clinical setting and the randomized trials comparing chemo-surgery versus definitive radiotherapy or CCRT. The combination of paclitaxel plus ifosfamide plus cisplatin (TIP regimen) obtained the highest rates of optimal pathological response, associated with elevated hematological toxicity. In a recent phase II study, a dose-dense regimen consisting of weekly paclitaxel plus carboplatin for 9 cycles has achieved optimal pathological response rates similar to those of TIP with better toxicity profile. Further studies are strongly warranted to better define the optimal regimen for the patients selected to receive NACT followed by radical surgery. GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries have shown 569,874 new cases of cervical cancer and 311,365 deaths due to this malignancy in 2018 (1). Concurrent cisplatin (CDDP)-based chemotherapy and radiotherapy (CCRT) plus brachytherapy represents the standard of care in patients with locally advanced disease, i.e. in stage FIGO 2009 Ib2-IIa2-IIb-III-IVa (2-6). A meta-analysis of 13 randomized trials showed that CCRT significantly improved 5year overall disease-free survival (DFS) [hazard ratio (HR)=0.78, 95% confidence interval (CI)=0.70-0.87], 5-year loco-regional disease-free survival (HR=0.76, 95%CI=0.68-0.86), 5-year metastases-free survival (HR=0.81, 95%CI=0.72-0.91) and 5year overall survival (OS) (HR=0.81, 95%CI=0.71-0.91) compared to radiotherapy alone (7). A larger survival advantage emerged for the two further trials in which adjuvant chemotherapy was administered after CCRT. An additional trial appeared to confirm the clinical benefit of this adjuvant treatment (8). In in vitro studies gemcitabine (GEM) was found to synergize with CDDP and have a radiosensitizing effect in six cervical cancer cell lines (9). A Mexican phase III trial randomized 515 patients with stage IIb-IVa cervical cancer to receive either CCRT (with CDDP 40 mg/m 2 + GEM 125 mg/m 2 weekly) plus brachytherapy followed by two cycles of adjuvant chemotherapy with CDDP (50 mg/m 2 day 1) + GEM 1000 mg/m 2 (days 1 and 8) every 3 weeks or the standard CCRT (with CDDP 40 mg/m 2 weekly) plus brachytherapy (8). The former arm experienced a trend significantly lower distant recurrence rate (8.1% versus 16.4%, p=0.005) a trend to a lower local recurrence rate (11.2% versus 16.4%, p=0.097), a significantly better progression-free survival (PFS) (HR=0.68, 95%CI=0.49-0.95) and a significantly better OS (HR=0.68, 95%CI=0.49-0.95), associated with increased, but manageable toxicity. Further investigations are needed to clarify the role of adjuvant chemotherapy after CCRT, especia...

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Section: Neoadjuvant Chemotherapy Followed By Radical Surgerymentioning

confidence: 82%

Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: Review of the Literature and Perspectives of Clinical Research

Gadducci

Cosio

2020

Anticancer Res

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“…Surgery combined with preoperative neoadjuvant chemotherapy (intravenous or arterial infusion chemotherapy) is clinically employed to reduce tumor lesions and control subclinical metastases [ 12 , 13 ], and the commonly used chemotherapeutic agents include cisplatin, carboplatin, paclitaxel, bleomycin, ifosfamide, and fluorouracil [ 13 ]. Traditional open radical hysterectomy for cervical cancer includes extensive hysterectomy, bilateral adnexal resection, and pelvic lymph node dissection [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Laparoscopic Radical Hysterectomy Combined with Neoadjuvant Chemotherapy for Cervical Cancer Patients Effectively Improves Immune Function

Liu

Wang

et al. 2022

Disease Markers

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Objective. To evaluate the clinical efficacy of neoadjuvant chemotherapy plus laparoscopic radical hysterectomy for cervical cancer and the effect on the immune function of patients. Methods. Between January 2021 and December 2021, 42 patients with cervical cancer diagnosed and treated at our hospital were recruited and randomly assigned at a 1 : 1 ratio to receive neoadjuvant chemotherapy plus open radical hysterectomy (control group) or neoadjuvant chemotherapy plus laparoscopic radical hysterectomy (treatment group) (study group). Outcome measures included surgical indices, clinical outcomes, and immunological function. Results. There were no significant differences in the operative time between the two groups ( P > 0.05 ). Patients receiving laparoscopic surgery had significantly less intraoperative bleeding and shorter time lapse before postoperative anal exhaustion, time lapse before out-of-bed activities, and hospital stay versus patients receiving open surgery ( P < 0.05 ). Laparoscopic surgery resulted in a significantly higher efficacy (90.48%) versus open surgery (57.14%) ( P < 0.05 ). After treatment, patients in the study group showed lower levels of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and cancer antigen (CA125) than those in the control group ( P < 0.05 ). After treatment, patients given laparoscopic surgery showed significantly lower CD3+, CD4+, and CD8+ levels and higher CD4+/CD8+ levels versus those with open surgery ( P < 0.05 ). The postoperative conditions of the two groups, including recatheterization, postoperative blood transfusion, and secondary anti-inflammation were not significantly different ( P > 0.05 ). The study group showed a significantly lower incidence of complications (19.05%) than the control group (71.43%) ( P < 0.05 ). Patients in the study group had a lower reoperation rate and a higher survival rate (0.00%, 95.24%) than those in the control group (19.05%, 66.67%) ( P < 0.05 ). Conclusion. Neoadjuvant chemotherapy plus laparoscopic radical hysterectomy effectively improves clinical efficacy, lowers cancer marker levels, improves patients’ immune function, reduces the risk of adverse events, and improves patients’ prognosis with less intraoperative bleeding, less trauma, faster postoperative recovery, and shorter hospital stay for cervical cancer patients.

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“…The response rates after NACT (79.2%) and after CCRT (90.0%) in our trial were similar to those reported in other studies [ 9 , 10 ]. The three-year PFS and OS might be higher than those reported in other studies (studies using dose-dense NACT followed by the CCRT strategy are listed in Table 4 [ 8 – 10 , 30 , 31 ]).…”

Section: Discussionmentioning

confidence: 61%

Neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation for locally advanced cervical cancer

Wang

et al. 2023

BMC Cancer

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Background Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). Forty percent of patients present with disease recurrence. This study aims to investigate the feasibility, safety and efficacy of neoadjuvant chemotherapy (NACT) with weekly cisplatin and paclitaxel (TP) followed by CCRT. Methods We are conducting a phase III trial comparing the efficacy and side effects of patients with cervical cancer (FIGO 2018 stage IIB to IVA) who were assigned to four cycles of NACT with cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly followed by CCRT or CCRT alone. In this report, we studied the medium-term effect of 50 patients enrolled in the NACT + CCRT arm. The primary endpoints were the response rate post-NACT and 12 weeks post-CCRT evaluated by MR/CT based on RECIST v 1.1. The secondary endpoints were 3-year OS (overall survival) and PFS (progression-free survival) measured by the Kaplan–Meier method. Results Among 50 patients enrolled in the NACT + CCRT arm, the complete and partial response rates were 10.4% and 68.8%, post-NACT. Twelve weeks after treatment completion, the complete response rate was 72.0%, whereas the total response rate (complete and partial response) was 90.0%. After a median follow-up of 28 months, the 3-year OS rate was 83.9%, and the 3-year PFS rate was 73.6%. NACT response was related to superior PFS and OS compared with NACT nonresponse (P < 0.01). Late AEs were exiguous, while early AEs mainly included myelosuppression and gastrointestinal AEs. Conclusions This study showed a good response rate achieved by dose-dense weekly cisplatin and paclitaxel followed by standard CCRT. The treatment regimen is feasible, as evidenced by the acceptable toxicity of NACT and by the high compliance with radiotherapy. Trial registration Protocol version number and date. Chinese clinical trial registry, ChiCTR1900025327; http://www.chictr.org.cn. Registered 24 August 2019. Retrospectively registered, medresman.org.cn/ChiCTR1900025326. The date recruitment began 01–01-2019.

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Dose-dense Paclitaxel- and Carboplatin-based Neoadjuvant Chemotherapy Followed by Surgery or Concurrent Chemoradiotherapy in Cervical Cancer: a Preliminary Analysis

Abstract: Dose-dense NACT seems to achieve promising RRs with manageable toxicity in cervical cancer. Investigation on larger series with longer follow-up is warranted.

Cited by 18 publications

References 37 publications

Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: Review of the Literature and Perspectives of Clinical Research

Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: Review of the Literature and Perspectives of Clinical Research

Laparoscopic Radical Hysterectomy Combined with Neoadjuvant Chemotherapy for Cervical Cancer Patients Effectively Improves Immune Function

Neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation for locally advanced cervical cancer

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