Treatment Therapies

Chemotherapy

Unmet clinical need in advanced NSCLC

As long as the majority of patients continue to present with stage IIIB/IV unresectable NSCLC, the prognosis for this disease will remain poor. Although the use of chemotherapy has seen an incremental improvement in terms of survival following the introduction of cisplatin-based therapies (second generation), and more recently the taxanes, antimetabolites and vinca alkaloids (third generation), the rates of improvement have slowed. Further, the use of chemotherapy and its limited efficacy has raised the issue of second-line treatment and the most effective agent currently used in this setting (docetaxel) is dose limited by its significant toxicity. Many patients, especially the elderly or those with a poor PS, are not suitable for chemotherapy, as they are not considered able to withstand the toxic insult. For many patients, and especially those with refractory or relapsed disease, there is an unmet clinical need for therapies that are convenient to administer and that can provide symptom relief without significant side effects.

A new generation of anticancer agents is being developed based on an increased understanding of the molecular and cellular processes underlying tumour biology and metastatic spread. This knowledge has led to the development of new targeted therapies that in general terms may be differentiated from previous agents by their cytostatic, rather than overtly cytotoxic action.¹ These new therapies can be classified according to the specific processes of tumour biology that they target.

• HER1/EGFR family inhibitors: small-molecule inhibitors of tyrosine-kinase (TK) activity, antibodies that inhibit HER1/EGFR activation.
• Angiogenesis inhibitors: small-molecule inhibitors of TK activity, small molecules that act as matrix metalloproteinase inhibitors, and antibodies that inhibit vascular endothelial growth factor receptors (VEGFR)
• Signal transduction inhibitors: antisense technology directed against phosphokinase C-alpha or RAS signalling.
• Modulators of apoptotic activity: antisense technology directed against expression of the anti-apoptosis bcl-2 protein.
• Eicosinoid pathway inhibitors: small molecules that inhibit cyclooxygenase-2 and 5-lipooxygenase activity.

Treatment Therapies

• Overview
• Chemotherapy
  • Adjuvant and Neoadjuvant
  • First-line Therapy
  • Second-line Therapy
  • Unmet clinical need in NSCLC
• Targeted therapies
• Current Therapy - Erlotinib