Tratamiento del cáncer de cabeza y cuello en el año 2013 Dra. Elvira del Barco Morillo

Hospital Clínico Universitario, Salamanca

Cáncer de cabeza y cuello en el año 2013

Intensificación quimiorradioterapia Quimiorradioterapia versus Biorradioterapia Tratamiento Inducción Enfermedad metástasica/recurrente

Intensificación quimiorradioterapia

Stages III and IV* SCC of: • oropharynx • hypopharynx • larynx (n=720)

R

Accelerated RT Cisplatin

Accelerated RT Cisplatin CETUXIMAB

Ongoing RTOG phase III trial (0522)

Total laryngectomy + postoperative RT

Response evaluation by

endoscopy and CT scan

R

<PR

≥PR TPF

3 cycles, 1 cycle q3 weeks

RT Cisplatin

RT CETUXIMAB

QUIMIORRADIOTERAPIA VS BIORRADIOTERAPIA

Giralt J, et al. Eur J Cancer Suppl 2009; 7 (2):476, abstract P-8.516.

ClinicalTrials.gov identifier: NCT00547157; www.amgentrials.com; protocol ID: 20062079.

CONCERT 2 (Randomised Phase 2)

Radiation + Panitumumab or Cisplatin in 1st-line Treatment of Stage III or IVa-b (M0) SCCHN

RT +

cisplatin 100 mg/m2

(on days 1 , 22 y 43 of RT)

RT +

panitumumab 9 mg/kg

(on days 1, 22 and 43 of RT)

RT: Accelerated fractionation radiation therapy with 70 to 72 Gy delivered over 6 to 6.5 weeks; fracionamiento standar

Intensity-modulated (IMRT) or three-dimensional conformal modality (3D-CRT)

E n d

o f t r e a t

m e n t

L o n g t e r m f o l l o w

u p

2:3

Unresected, locally

advanced SCCHN (n=150)

R

Stratification by:

• Site of primary tumour

• RT delivery modality

• Nodal status (N0 vs. N+)

• Tumour stage (T1-3 vs. T4)

Primary Endpoint: LRC rate at 2 years

QUMIOTERAPIA DE INDUCCIÓN

ESTUDIO TTCC 2503 ESTUDIO “DECIDE” ESTUDIO “PARADIGM” ESTUDIO PACAGNELLA ET AL ESTUDIO GRUPO SHANGAI.

TPF Docetaxel 75 mg/m2 Día 1 Cisplatino 75 mg/m2 Día 1

5-FU 750 mg/m2 PC, Días 1-5 Cada 3 semanas por 4 ciclos

PF Cisplatino 100 mg/m2 Día 1

5-FU 1000 mg/m2 PC, Días 1-5 Cada 3 semanas por 4 ciclos

Localmente avanzado

irresecable (N = 310)

QTRT RT 66-70 Gy Cisplatino

100 mg/m2 Días 1, 22, 43

Sin Inducción

Cirugía de rescate si enfermedad residual antes o después de

RT

Orofaringe 40%

Laringe 20%

Hipofaringe 20%

C. Oral 20%

Estudio 2503 Grupo español de TTCC.

Objetivo primario: TTF ( evaluables)

E N Number of patients at risk

157 234 120 78 48 26 10

96 119 36 26 17 11 4

ICT + CRT

CRT

(months)

CRT; median 5.0 months

HR = 0.57; 95% CI, 0.45–0.74; p<0.0001

ICT + CRT; median 12.5 months

Estudio 2503 Grupo español de TTCC

DeCIDE: A phase III randomized trial of docetaxel (D), cisplatin (P), 5-

fluorouracil (F) (TPF) induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck (SCCHN)

Ezra E. W. Cohen, Theodore Karrison, Masha Kocherginsky, Chao H Huang, Mark Agulnik, Bharat Bhushan Mittal, Furhan Yunus, Sandeep Samant, Bruce Brockstein, Luis E. Raez, Ranee Mehra, Priya Kumar, Frank G. Ondrey, Tanguy Y. Seiwert, Victoria Meucci Villaflor, Daniel J. Haraf, Everett E. Vokes

N2/N3

TPF x 2 ciclos QTRT RT hiperfracionada +

DFHX

QTRT RT hiperfracionada +

DFHX

5 days of Docetaxel (25 mg/m2), FU (600 mg/m2), hydroxyurea (500 mg BID), and RT (150 cGy BID) followed by a 9 day break

D (75 mg/m2), P (75 mg/m2), F (750 mg/m2 day 1-5)

400 pt

280 pt.

2004-2009

The PARADIGM trial: A phase III study comparing sequential therapy (ST) to

concurrent chemoradiotherapy (CRT) in locally advanced head and neck cancer (LANHC).

Robert I. Haddad, Guilherme Rabinowits, Roy B. Tishler, Douglas Adkins, Fadlo Raja Khuri, Joseph Clark, Jochen H. Lorch, Sewanti Atul Limaye, Lori J. Wirth, Anne O'Neill, Sarah Riley, Marshall R. Posner

Estadio III/IV TPF x 3 ciclos

D (75 mg/m2), P (100 mg/m2), F (1000mg/m2 day 1-4) 330 pt. ESPERADOS 145 RECLUTADOS 08/04-12/08

NR

CR

DOCETAXEL SEMANAL x4 RT ACELERADA BOOST (1-5)

6 SEMANAS A1

CARBOPLATINO SEMANAL

RT (1-5) x7 SEMANAS. A2

CISPATINO SEMANA (1,4) RT ACELERADA BOOST (1-5)

6 SEMANAS. B

A

TPF x 3

Localmente avanzado

irresecable (N =420)

QT-RT (PF x2)

RT- cetuximab

TPF x3

QT-RT (PF x2)

RT- cetuximab

C. Oral OroF. HipoF.

1, SG a 3 años entre Inducción vs No inducción

2, Incidencia de toxicidad grado 3-4 entre QTRT vs RT-cetX.

Cetuximab/RT versus concomitant CT/RT with or without induction TPF in locally advanced H&N squamous cell carcinoma. Preliminary toxicity results of a randomized, 2x2 factorial,

phase II-III study (NCT01086826)

Estadio III/IV

ORAL 256 PACIENTES RESECABLES

TPF x 2 ciclos CIRUGIA RT

CIRUGIA- RT

Enfermedad metástasica/recurrente. PACLITAXEL + CETUXIMAB. ERBITAX.

TPEx. Estudio GORTEC 2008-03

CDDP+5FU VS CDDP + 5FU+ PANITUMUMAB. SPECTRUM.

GEFITINIB + DOCETAXEL VS DOCETAXEL

Cisplatin 100 mg/m2 +

5-FU 1000 mg/m2/d x 4d (Q3W for max. 6 cycles)

Cisplatin 100 mg/m2 +

5-FU 1000 mg/m2/d x 4d +

panitumumab 9 mg/kg (Q3W for 6 cycles)

Recurrent or metastatic

SCCHN (n=657)

R

1:1

Stöhlmacher J, et al. Eur J Cancer Suppl 2009; 7 (2):474, abstract P-8.514.

ClinicalTrials.gov identifier: NCT00460265; www.amgentrials.com; protocol ID: 20050251.

Chemotherapy ± Panitumumab in 1st-line Treatment of Recurrent or Metastatic SCCHN

Stratification by:

• Site of primary tumour

• Disease status

• Performance status (ECOG 0 vs.1)

E n d

o f t r e a t

m e n t

L o n g t e r m f o l l o w

u p

Maintance

panitumumab

monotherapy

Primary Endpoint: Overall survival (OS)

Secondary endpoints: Progression-free survival (PFS) Overall response rate (ORR) Duration of response (DoR) Time to progression (TTP) Safety

SPECTRUM

Estadio III/IV

270 pac irresecables o metastásico

Docetaxel semanal

Docetaxel semanal + Gefitinb