Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Carcinoma, Squamous Cell

Esophageal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Fluorouracil

Cisplatin

Panitumumab

Antineoplastic Agents, Immunological

Day -7, day +15 and day +36: panitumumab 9.0 mg/kg i.v. Day +1 to +39: radiation therapy 1.8 Gy fractions 5 times per week to a cumulative dose of 50.4 Gy Day +1 and +29: cisplatin 75 mg/m2 i.v. Day +1 to +4 and +29 to +32: 5-fluorouracil 1000 mg/m2 i.v.

CRT + Panitumumab

Day +1 to +39: radiation therapy 1.8 Gy fractions 5 times per week to a cumulative dose of 50.4 Gy Day +1 and +29: cisplatin 75 mg/m2 i.v. Day +1 to +4 and +29 to +32: 5-fluorouracil 1000 mg/m2 i.v.

Concurrent chemoradiation therapy without panitumumab

C.M.L. van Herpen, Md PhD

For esophageal cancer that can not be removed by surgery, the choice of treatment is a combination of chemotherapy and radiotherapy. We call this combination- (or concurrent) chemoradiotherapy. Chemotherapy is treatment with drugs that kill cancer cells. Both chemotherapy and radiotherapy make the tumour smaller and enhance each other's effect. The goal of treatment with chemotherapy and radiation therapy is to cure the cancer. Unfortunately only a small proportion of patients are cured with this treatment.

Improvements in the outcome of treatment may be expected by using the so-called "targeted" treatments. With esophageal cancer, a protein (the epidermal growth factor receptor (this is a kind of trap), the EGFR), is present in many tumours. This protein causes the tumor to grow. Panitumumab is a drug that blocks the functioning of this receptor (catcher), so that possibly the growth and spread of esophageal cancer is prevented.

The main objective of this trial is to see if survival of patients with inoperable esophageal cancer improves as panitumumab is added to standard treatment with chemoradiotherapy.

It will also investigate whether patients tolerate the addition of panitumumab to the standard treatment. Also, the biological characteristics of the tumor will be examined. In a proportion of patients it will be determined how the enhancement of the cancer is visible on an FDG-PET scan before the start of treatment and how this changes during the treatment. It will be also be evaluated how this treatment affects the survival.

A complete response rate of approximately 30% is achieved for standard treatment of irresectable carcinoma of the oesophagus, consisting of concurrent chemoradiation therapy (50.5 Gy + cisplatin/5-FU). Attempts to improve outcome by intensifying conventional cytotoxic drugs or increasing the radiation dose have not been successful. Future improvements will likely require the incorporation of targeted agents that probably will not add significant toxicity, the use of molecular predictors of response and early identification of responders. In both squamous cell carcinoma and adenocarcinoma of the oesophagus expression of EGFR is correlated with poor outcome. Furthermore the addition of cetuximab, a chimaeric EGFR antibody, to radiation therapy in head and neck cancer and non-small cell lung cancer showed a gain in overall survival. In head and neck cancer studies with the addition of panitumumab to chemo-radiation therapy are currently ongoing. Therefore, we propose to perform a randomised phase II study of chemo-radiation therapy with or without the combination of panitumumab (human EGFR antibody) in irresectable squamous cell carcinoma or adenocarcinoma of the oesophagus without distant metastases.

Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus

A Randomised Phase II Study of Radio-chemotherapy With or Without Panitumumab (Vectibix®) in Irresectable Squamous Cell Carcinoma or Adenocarcinoma of the Oesophagus

To describe the 1-year OS rate after concurrent CRT with or without panitumumab in irresectable carcinoma of the oesophagus. The control arm is used to validate whether the historical cohort used for comparison is similar to our success-rate.

Investigation of the acute and long-term toxicity of both study arms (according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0);

PFS: interval between randomisation date and the date at which disease progression is established being not suspicious for a second cancer (histologically confirmed when in doubt) or date of death from any cause but clearly not related to disease- or treatment (e.g. accident). Patients still disease-free after 18 months follow-up or lost to follow-up or death clearly not related to disease or treatment (e.g. accident)), are censored at the date of the most recent follow-up or at the analysis cut-off date, whichever comes first.

Response rate: partial (PR) or complete response (CR) according to RECIST 1.1 at 3 months after treatment

pharmacodynamics (PD) of panitumumab (EGFR, K-RAS, B-RAF, downstream signalling pathways ) compared between the biopsy at baseline (standard) and the biopsy one week after start chemo-radiation therapy

baseline, 7 days after the first panitumumab dose or for start chemo-radiation therapy. during treatment with chemoradiation therapy after three weeks.

2-4 weeks after finishing treatment. 10-12 weeks after finishing treatment

Spots Global Cancer Trial Database for irresectable squamous cell or adenocarcinoma of the oesophagus