The Role of Chemotherapy and Radiation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Abstract

Approximately one out of every three patients with non-small cell lung cancer (NSCLC) has locally advanced disease that is surgically unresectable. If their performance status allows, it is current practice to treat these patients with a combination of chemotherapy and external beam irradiation. There have been several studies supporting the addition of chemotherapy to radiation, particularly when delivered concurrently. There is debate over which treatment agents and schedules are most optimal, even with the most proven treatments delivering only modest results, with high rates of local and distant disease failure. Advances in imaging and radiation planning and delivery technology have allowed for the potential for improvement of the therapeutic ratio by reducing normal tissue exposure and ensuring for more precise delivery, while new systemic agents show promising activity in NSCLC. Pemetrexed is a pyrrolopyrimidine-based folate anti-metabolite that works by inhibiting a variety of enzymes of thymidylate and purine synthesis, thus leading to cell stasis and death. Similar to other cytotoxic antifolates, pemetrexed has been shown in pre-clinical study to act as an effective radiosensitizer. At present, it is being studied in phase I and II studies when combined with other systemic agents and radiation therapy in the treatment of locally advanced NSCLC, and the results have been promising. It has the advantage of allowing for relatively safe delivery of full systemic doses when combined other agents and radiation therapy, a distinction over combined modality treatments. Its efficacy, particularly in non-squamous NSCLC, in phase I and II studies has lead to investigations in the phase III setting where a more defined role for pemetrexed in locally advanced non-squamous NSCLC will potentially be defined. This review summarizes the use of combined modality treatment in locally advanced NSCLC, outlines recent advances in radiation planning and treatment, and reviews the current data on the use concurrent chemoradiation regimens featuring pemetrexed.

125I Brachytherapy in Locally Advanced Non-Small Cell Lung Cancer after Progression of Concurrent Radiochemotherapy

“…4,5 Therefore, chemotherapy combined with external beam radiotherapy has played a major role in the management of patients with unresectable lung cancer patients. 6,7 Numerous clinical studies have also confirmed the effectiveness of chemotherapy combined with radiotherapy in the treatment of advanced NSCLC, 8,9 which could prolong survival time and obviously improve the quality of life of patients. 10 However, at present, a great number of patients cannot tolerate the currently available treatment modalities mainly owing to their poor general condition, 11 tumor staging and grading, and severe toxicity after radiotherapy and chemotherapy (myelosuppression, nausea, vomiting, radiation pneumonitis, etc.…”

125I Brachytherapy in Locally Advanced Nonsmall Cell Lung Cancer After Progression of Concurrent Radiochemotherapy

“…4,5 Therefore, chemotherapy combined with external beam radiotherapy has played a major role in the management of patients with unresectable lung cancer patients. 6,7 Numerous clinical studies have also confirmed the effectiveness of chemotherapy combined with radiotherapy in the treatment of advanced NSCLC, 8,9 which could prolong survival time and obviously improve the quality of life of patients. 10 However, at present, a great number of patients cannot tolerate the currently available treatment modalities mainly owing to their poor general condition, 11 tumor staging and grading, and severe toxicity after radiotherapy and chemotherapy (myelosuppression, nausea, vomiting, radiation pneumonitis, etc.…”

¹²⁵I brachytherapy of locally advanced non-small-cell lung cancer after one cycle of first-line chemotherapy：a comparison with best supportive care

“…For patients with stage III NSCLC, treatments are delivered to the patients with a goal of achieving a local tumor control and preventing the systemic metastases 8. Chemotherapy, particularly combined with external beam radiotherapy, can offer some benefits of prolonging overall survival (OS) to the patients with advanced NSCLC 9–11. However, a large number of patients at an advanced tumor stage are not eligible for the currently available treatment modalities due to their poor general conditions and intolerability to severe toxicities after one or more cycles of first-line chemotherapy, especially the severe adverse events occurring in vital organs 12,13.…”