Radiotherapy With Cisplatin Versus Radiotherapy With Cetuximab After Induction Chemotherapy for Larynx Preservation

Groupe Oncologie Radiotherapie Tete et Cou

Status and phase

Completed

Phase 2

Conditions

Hypopharynx Cancer

Larynx Cancer

Treatments

Drug: cetuximab

Procedure: Radiotherapy 70 Gy, 35 fractions

Drug: Cisplatin

Study type

Interventional

Funder types

Other

Identifiers

NCT00169247

GORTEC-TREMPLIN

Details and patient eligibility

About

Larynx preservation remains a very challenging approach in patients with larynx/pharynx cancer. A first attempt consisted of induction chemotherapy followed in good responders by irradiation. This approach allowed to preserve 60 % of the larynx without any significant difference in survival. The second attempt consisted of concurrent chemo-irradiation. This approach provided a higher larynx preservation rate but survival remained unchanged and mucosal toxicity was also higher. A third approach is currently under evaluation: induction chemotherapy followed by concurrent chemo-irradiation in good responders.

Full description

At ASCO 2004 there were 3 major presentations issuing an increasing in survival:

the update of the MACH-NC meta-analysis showed that actually only concurrent chemo-irradiation trials found a significantly improved survival (in particular the addition of cisplatinum alone to radiotherapy) the addition of docetaxel to the cisplatinum-5FU regimen (TPF) when compared with cisplatinum--5FU (PF) the addition of cetuximab to irradiation

On this basis we decided to carry-out a randomized phase II for previously untreated patients requiring a total laryngectomy:

All patients after a complete work-up including a CTscan will receive 3 cycles of TPF(T: 75 mg/m², P: 75 mg/m² and 5FU 750 mg/m²).

Patients with response over 50 % (endoscopy and CTscan) will be randomized to receive either irradiation (70 Gy) and cisplatinum (100 mg/m² on D1, D22 and D43) or irradiation (70 Gy) with cetuximab (loading dose of 400 mg followed by weekly 250 mg for a total of 8 cycles.

Patients with less than 50% decease in tumour volume after TPF, patients with residual or recurrent disease after either RT-CDDP or RT-cetuximab will get salvage total laryngectomy.

Enrollment

156 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Larynx or hypopharynx squamous cell carcinoma proven by histology, locally advanced, only eligible for surgery as total or sub-total (pharyngo-)laryngectomy
Performance status 0-1
Neutrophils >=1.5 x 109/l, Platelets count >=100 x 109/l, haemoglobin >=10 g/dl
Total bilirubin <= 1.5 x upper reference range
ASAT and ALAT <= 2.5 x upper reference range, Alkaline Phosphatases <= 5 x upper reference range
Serum creatinine <= 120 µmol/l
Weight loss < 10 % within last 3 months
Written inform consent

Exclusion criteria