The definition of unresectable stage III lung cancer includes a tumor of any size invading surrounding structures (example heart, great vessels, mediastinum, trachea, esophagus, etc.), several tumor nodules in the ipsilateral lung, or mediastinal or supraclavicular nodal involvement, but no evidence of distant, metastatis (bone, liver, etc.).
The challenge in treating unresectable locally advanced lung cancer is preventing local recurrence as well as distant metastases.
Since the 90's trials have shown benefit by adding chemotherapy to radiation compared to radiation alone, proving that by adding systemic therapy patients survival improved.
The most commonly used drugs were cisplatin, vinblastine and carboplatin, which were used sequentially or concomitant with radiotherapy. Subsequent trials revealed that concomitant was better than sequential. The weekly combination of paclitaxel and carboplatin was effective and well tolerated and became a standard of care.
Cisplatin, etoposide, docetaxel and gemzar were all effective alternatives but proved to have higher toxicity.
In recent years pemetrexed a newer chemotherapy agent has successfully been combined with cisplatin or carboplatin. And even more recently molecular targeted agents have been tested. In EGFR mutated tumors, cetuximab (a monoclonal antibody) was added to paclitaxel and carboplatin with no additional benefit.
The antiangiogenic avastin (be-vacizumab) was tested as well but thought to be toxic combined with ra-diation causing esophageal perforation and bleeding.
The trick to optimizing therapy in the future will be how best to incorporate tumor biology (EGFR, ALK, and KRAS) to develop new more tailored therapeutic agents.