I-START

A Phase I/II trial of isotoxic accelerated radiotherapy in the treatment of patients with non-small cell lung cancer.

The I-START trial (ISoToxic Accelerated RadioTherapy for non-small cell lung cancer) was designed to determine the highest doses of radiotherapy that can safely be used in locally advanced non-small cell lung cancer (NSCLC). Evidence is available that suggests increasing the dose of radiotherapy given per fraction may improve both local control of the cancer and survival in some patients. However, high dose radiotherapy can damage normal tissues as well as the tumour. The dose of radiotherapy that can be used to treat lung cancer is limited by the normal tissues close to the cancer. For most of these normal tissues (lung, spinal cord and heart) the maximum safe radiotherapy dose that can be given is known. The maximum safe dose of radiotherapy for the oesophagus (gullet) is not currently known.

This is a non-randomised phase I/II trial where patients will either be entered into the phase I or phase II depending on whether their oesophagus is in the Planning Target Volume (PTV) (the high dose area) and whether the final oesophageal dose limit is known. Once the maximum tolerated dose (MTD) is known all patients will enter the phase II.

The Phase I part of the trial was to establish a safe dose of radiotherapy to the oesophagus, and was for those participants where the oesophagus will receive a high dose of radiation due to it lying close to the cancer. Patients were assigned a dose, which was given to groups of 6 patients, and then the dose increased if safe.

For those participants where the cancer is a safe distance from their oesophagus, the highest dose of radiotherapy that does not exceed the known safe dose limits of the normal structures (lung, spinal cord and heart) was used. At the time of recruitment, maximum dose was allocated. The dose for each patient was then individualised before start of treatment so that the normal tissues did not receive a dose above the maximum safe radiotherapy dose. The individualisation of dose in this way was a novel approach.

The aim of this study was to determine whether increasing the dose of radiotherapy for NSCLC patients is a tolerable, safe and effective treatment.

The results are currently being analysed and there is the potential that this new approach to treatment may be compared against the best currently available standard treatments in a future larger randomised (Phase III) trial.