Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial

M G Ghi, A Paccagnella, D Ferrari, P Foa, D Alterio, C Codecà, F Nolè, E Verri, R Orecchia, F Morelli, S Parisi, C Mastromauro, C A Mione, C Rossetto, M Polsinelli, H Koussis, L Loreggian, A Bonetti, F Campostrini, G Azzarello & 18 others C D'Ambrosio, F Bertoni, C Casanova, E Emiliani, M Guaraldi, F Bunkheila, P Bidoli, R M Niespolo, A Gava, E Massa, A Frattegiani, F Valduga, G Pieri, T Cipani, D Da Corte, F Chiappa, E Rulli, GSTTC (Gruppo di Studio Tumori della Testa e del Collo) Italian Study Group

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Abstract

Background: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy.

Materials and methods: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level).

Results: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF.

Conclusions: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy.

Clinical Trial Number: NCT01086826, www.clinicaltrials.gov.

Original languageEnglish
Pages (from-to)2206-2212
Number of pages7
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Volume28
Issue number9
DOIs
Publication statusPublished - Sep 1 2017

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Induction Chemotherapy
Head and Neck Neoplasms
Survival
docetaxel
Therapeutics
varespladib methyl
Platinum
Fluorouracil
Cisplatin
Disease-Free Survival
Randomized Controlled Trials
Clinical Trials
Cetuximab

Keywords

  • Journal Article

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Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial. / Ghi, M G; Paccagnella, A; Ferrari, D; Foa, P; Alterio, D; Codecà, C; Nolè, F; Verri, E; Orecchia, R; Morelli, F; Parisi, S; Mastromauro, C; Mione, C A; Rossetto, C; Polsinelli, M; Koussis, H; Loreggian, L; Bonetti, A; Campostrini, F; Azzarello, G; D'Ambrosio, C; Bertoni, F; Casanova, C; Emiliani, E; Guaraldi, M; Bunkheila, F; Bidoli, P; Niespolo, R M; Gava, A; Massa, E; Frattegiani, A; Valduga, F; Pieri, G; Cipani, T; Da Corte, D; Chiappa, F; Rulli, E; GSTTC (Gruppo di Studio Tumori della Testa e del Collo) Italian Study Group.

In: Annals of oncology : official journal of the European Society for Medical Oncology, Vol. 28, No. 9, 01.09.2017, p. 2206-2212.

Research output: Contribution to journalArticle

Ghi, MG, Paccagnella, A, Ferrari, D, Foa, P, Alterio, D, Codecà, C, Nolè, F, Verri, E, Orecchia, R, Morelli, F, Parisi, S, Mastromauro, C, Mione, CA, Rossetto, C, Polsinelli, M, Koussis, H, Loreggian, L, Bonetti, A, Campostrini, F, Azzarello, G, D'Ambrosio, C, Bertoni, F, Casanova, C, Emiliani, E, Guaraldi, M, Bunkheila, F, Bidoli, P, Niespolo, RM, Gava, A, Massa, E, Frattegiani, A, Valduga, F, Pieri, G, Cipani, T, Da Corte, D, Chiappa, F, Rulli, E & GSTTC (Gruppo di Studio Tumori della Testa e del Collo) Italian Study Group 2017, 'Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial', Annals of oncology : official journal of the European Society for Medical Oncology, vol. 28, no. 9, pp. 2206-2212. https://doi.org/10.1093/annonc/mdx299
Ghi, M G ; Paccagnella, A ; Ferrari, D ; Foa, P ; Alterio, D ; Codecà, C ; Nolè, F ; Verri, E ; Orecchia, R ; Morelli, F ; Parisi, S ; Mastromauro, C ; Mione, C A ; Rossetto, C ; Polsinelli, M ; Koussis, H ; Loreggian, L ; Bonetti, A ; Campostrini, F ; Azzarello, G ; D'Ambrosio, C ; Bertoni, F ; Casanova, C ; Emiliani, E ; Guaraldi, M ; Bunkheila, F ; Bidoli, P ; Niespolo, R M ; Gava, A ; Massa, E ; Frattegiani, A ; Valduga, F ; Pieri, G ; Cipani, T ; Da Corte, D ; Chiappa, F ; Rulli, E ; GSTTC (Gruppo di Studio Tumori della Testa e del Collo) Italian Study Group. / Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial. In: Annals of oncology : official journal of the European Society for Medical Oncology. 2017 ; Vol. 28, No. 9. pp. 2206-2212.
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title = "Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial",
abstract = "Background: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy.Materials and methods: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12{\%} (HR 0.675, with 80{\%} power at two-sided 5{\%} significance level).Results: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95{\%} CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF.Conclusions: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy.Clinical Trial Number: NCT01086826, www.clinicaltrials.gov.",
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TY - JOUR

T1 - Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial

AU - Ghi, M G

AU - Paccagnella, A

AU - Ferrari, D

AU - Foa, P

AU - Alterio, D

AU - Codecà, C

AU - Nolè, F

AU - Verri, E

AU - Orecchia, R

AU - Morelli, F

AU - Parisi, S

AU - Mastromauro, C

AU - Mione, C A

AU - Rossetto, C

AU - Polsinelli, M

AU - Koussis, H

AU - Loreggian, L

AU - Bonetti, A

AU - Campostrini, F

AU - Azzarello, G

AU - D'Ambrosio, C

AU - Bertoni, F

AU - Casanova, C

AU - Emiliani, E

AU - Guaraldi, M

AU - Bunkheila, F

AU - Bidoli, P

AU - Niespolo, R M

AU - Gava, A

AU - Massa, E

AU - Frattegiani, A

AU - Valduga, F

AU - Pieri, G

AU - Cipani, T

AU - Da Corte, D

AU - Chiappa, F

AU - Rulli, E

AU - GSTTC (Gruppo di Studio Tumori della Testa e del Collo) Italian Study Group

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy.Materials and methods: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level).Results: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF.Conclusions: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy.Clinical Trial Number: NCT01086826, www.clinicaltrials.gov.

AB - Background: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy.Materials and methods: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level).Results: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF.Conclusions: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy.Clinical Trial Number: NCT01086826, www.clinicaltrials.gov.

KW - Journal Article

U2 - 10.1093/annonc/mdx299

DO - 10.1093/annonc/mdx299

M3 - Article

VL - 28

SP - 2206

EP - 2212

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 9

ER -