Treatment Strategies

Locally advanced disease (stage IIIB, also includes some stage IIIA tumours with bulky N2)

Approximately 25% of patients with NSCLC present with locally advanced, stage IIIB disease that is considered to be unresectable (i.e. not suitable for surgery). For many years the conventional treatment for this condition was irradiation to the chest. As discussed above, this strategy has the potential to control the primary tumour and involved local lymph nodes, but has little effect on distant micro-metastases that would not be evident from clinical staging procedures. Up until the late 1980s, patients received conventional external beam radiotherapy at a dose of 60 Gy and median survival was less than 1 year and survival rates at 2 and 5 years were 15% and 5%, respectively. Since then, the development of radiotherapy procedures including innovative dosing schedules, such as the continuous hyperfractionated accelerated radiotherapy (CHART) model, have led to modest improvements in survival rates.¹

In theory, chemotherapy can enhance the effectiveness of radiotherapy and this has been explored extensively. Several different approaches have been considered:

• Several large studies have compared radiotherapy alone with radiotherapy either followed by or preceded by chemotherapy (sequential administration) and have, for example, found improvements in the chemoradiotherapy arm for median survival from 9.6 months to 13.7 months.² Such combinations inevitably increase toxicity, but are nonetheless reasonably well tolerated.
  
  
• Several agents commonly used in the treatment of lung cancer are known to increase the sensitivity of cancer cells when administered before commencing a course of radiotherapy (often referred to as radiosensitisation or induction therapy). One study compared induction therapy followed by radiotherapy followed by further chemotherapy in one arm, with radiotherapy alone in the other. Although median survival in the chemoradiation arm was only improved from 10 months to 12 months, there was a significant survival advantage at 2 years (21% vs 14%, p=0.08).²² Some of the third-generation drugs (such as docetaxel, which blocks mitosis) are highly efficient radiosensitisers.
  
  
• Several studies have demonstrated superior survival in patients treated with concurrent chemotherapy and radiotherapy compared with sequential chemoradiotherapy, whereas in other studies the results are less clear.²⁰ Although concomitant chemoradiotherapy is associated with increased toxicity, especially irritation or inflammation of the oesophagus, a specific QoL study found that patients considered that the benefits of improved survival outweighed the side effects.³
  
  
• Induction chemotherapy followed by chemoradiotherapy has also been investigated with promising results, although toxicity is a major issue. Evidence-based guidelines for the treatment of NSCLC have been published, including those recommended by the American Society of Clinical Oncology.⁴ In particular, the combination of radiation therapy with chemotherapy is now recommended as the standard of care for patients with locally-advanced disease.^4,5

Treatment Strategies

• Overview
• Early Stage
• Locally Advanced Stage
• Advanced Stage
• Future Strategies