Neo-adjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients: A phase II study

Gabriella Ferrandina, Eleonora Palluzzi, Valerio Gallotta, Maria Antonietta Gambacorta, Rosa Autorino, Luigi Carlo Turco, Gabriella Macchia, Francesco Cosentino, Benedetta Gui, Maria Vittoria Mattoli, Graziana Ronzino, Vincenzo Valentini, Giovanni Scambia

Research output: Contribution to journalArticle

Abstract

PURPOSE: The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced cervical cancer (LACC) patients.

METHODS AND MATERIALS: The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m2, carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients.

RESULTS: 45 patients were enrolled into the study; 25 patients (55.5%) were FIGO stage IIB, 9 cases (20.0%) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4%) patients; pCR was documented in 18 out of 40 patients (45.0%). Grade 3-4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0% and 86.0%, respectively.

CONCLUSIONS: NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity.

Original languageEnglish
Pages (from-to)1062-1068
Number of pages7
JournalEuropean Journal of Surgical Oncology
Volume44
Issue number7
DOIs
Publication statusPublished - Jul 2018

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Platinum
Uterine Cervical Neoplasms
Drug Therapy
Intensity-Modulated Radiotherapy
Carboplatin
Paclitaxel
Sample Size
Area Under Curve
Lymph Nodes
Safety

Keywords

  • Adenocarcinoma/mortality
  • Adult
  • Aged
  • Antineoplastic Agents/therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Carboplatin/administration & dosage
  • Carcinoma, Squamous Cell/mortality
  • Chemoradiotherapy/methods
  • Cisplatin/therapeutic use
  • Disease-Free Survival
  • Female
  • Humans
  • Hysterectomy
  • Intention to Treat Analysis
  • Lymph Node Excision
  • Lymph Nodes/pathology
  • Middle Aged
  • Neoadjuvant Therapy/methods
  • Paclitaxel/administration & dosage
  • Pelvis
  • Postoperative Complications/epidemiology
  • Radiotherapy, Intensity-Modulated/methods
  • Survival Rate
  • Treatment Outcome
  • Uterine Cervical Neoplasms/mortality

Cite this

Neo-adjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients : A phase II study. / Ferrandina, Gabriella; Palluzzi, Eleonora; Gallotta, Valerio; Gambacorta, Maria Antonietta; Autorino, Rosa; Turco, Luigi Carlo; Macchia, Gabriella; Cosentino, Francesco; Gui, Benedetta; Mattoli, Maria Vittoria; Ronzino, Graziana; Valentini, Vincenzo; Scambia, Giovanni.

In: European Journal of Surgical Oncology, Vol. 44, No. 7, 07.2018, p. 1062-1068.

Research output: Contribution to journalArticle

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abstract = "PURPOSE: The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced cervical cancer (LACC) patients.METHODS AND MATERIALS: The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m2, carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients.RESULTS: 45 patients were enrolled into the study; 25 patients (55.5{\%}) were FIGO stage IIB, 9 cases (20.0{\%}) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4{\%}) patients; pCR was documented in 18 out of 40 patients (45.0{\%}). Grade 3-4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0{\%} and 86.0{\%}, respectively.CONCLUSIONS: NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity.",
keywords = "Adenocarcinoma/mortality, Adult, Aged, Antineoplastic Agents/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Carboplatin/administration & dosage, Carcinoma, Squamous Cell/mortality, Chemoradiotherapy/methods, Cisplatin/therapeutic use, Disease-Free Survival, Female, Humans, Hysterectomy, Intention to Treat Analysis, Lymph Node Excision, Lymph Nodes/pathology, Middle Aged, Neoadjuvant Therapy/methods, Paclitaxel/administration & dosage, Pelvis, Postoperative Complications/epidemiology, Radiotherapy, Intensity-Modulated/methods, Survival Rate, Treatment Outcome, Uterine Cervical Neoplasms/mortality",
author = "Gabriella Ferrandina and Eleonora Palluzzi and Valerio Gallotta and Gambacorta, {Maria Antonietta} and Rosa Autorino and Turco, {Luigi Carlo} and Gabriella Macchia and Francesco Cosentino and Benedetta Gui and Mattoli, {Maria Vittoria} and Graziana Ronzino and Vincenzo Valentini and Giovanni Scambia",
note = "Copyright {\circledC} 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.",
year = "2018",
month = "7",
doi = "10.1016/j.ejso.2018.04.019",
language = "English",
volume = "44",
pages = "1062--1068",
journal = "European Journal of Surgical Oncology",
issn = "0748-7983",
publisher = "W.B. Saunders Ltd",
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TY - JOUR

T1 - Neo-adjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients

T2 - A phase II study

AU - Ferrandina, Gabriella

AU - Palluzzi, Eleonora

AU - Gallotta, Valerio

AU - Gambacorta, Maria Antonietta

AU - Autorino, Rosa

AU - Turco, Luigi Carlo

AU - Macchia, Gabriella

AU - Cosentino, Francesco

AU - Gui, Benedetta

AU - Mattoli, Maria Vittoria

AU - Ronzino, Graziana

AU - Valentini, Vincenzo

AU - Scambia, Giovanni

N1 - Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

PY - 2018/7

Y1 - 2018/7

N2 - PURPOSE: The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced cervical cancer (LACC) patients.METHODS AND MATERIALS: The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m2, carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients.RESULTS: 45 patients were enrolled into the study; 25 patients (55.5%) were FIGO stage IIB, 9 cases (20.0%) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4%) patients; pCR was documented in 18 out of 40 patients (45.0%). Grade 3-4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0% and 86.0%, respectively.CONCLUSIONS: NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity.

AB - PURPOSE: The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced cervical cancer (LACC) patients.METHODS AND MATERIALS: The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m2, carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients.RESULTS: 45 patients were enrolled into the study; 25 patients (55.5%) were FIGO stage IIB, 9 cases (20.0%) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4%) patients; pCR was documented in 18 out of 40 patients (45.0%). Grade 3-4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0% and 86.0%, respectively.CONCLUSIONS: NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity.

KW - Adenocarcinoma/mortality

KW - Adult

KW - Aged

KW - Antineoplastic Agents/therapeutic use

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Carboplatin/administration & dosage

KW - Carcinoma, Squamous Cell/mortality

KW - Chemoradiotherapy/methods

KW - Cisplatin/therapeutic use

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Hysterectomy

KW - Intention to Treat Analysis

KW - Lymph Node Excision

KW - Lymph Nodes/pathology

KW - Middle Aged

KW - Neoadjuvant Therapy/methods

KW - Paclitaxel/administration & dosage

KW - Pelvis

KW - Postoperative Complications/epidemiology

KW - Radiotherapy, Intensity-Modulated/methods

KW - Survival Rate

KW - Treatment Outcome

KW - Uterine Cervical Neoplasms/mortality

U2 - 10.1016/j.ejso.2018.04.019

DO - 10.1016/j.ejso.2018.04.019

M3 - Article

C2 - 29753611

VL - 44

SP - 1062

EP - 1068

JO - European Journal of Surgical Oncology

JF - European Journal of Surgical Oncology

SN - 0748-7983

IS - 7

ER -