Concurrent Chemoradiotherapy for Unresectable Stage III Non–Small Cell Lung Cancer

Abstract

Over the last two decades, several approaches to multimodality therapy have been investigated in patients with advanced unresectable non^small cell lung cancer. These include induction chemotherapy and concurrent chemoradiotherapy. Both approaches have been shown to be superior to radiation therapy alone. However, in several randomized trials, concomitant chemoradiotherapy was shown to be superior to the induction chemotherapy approach. It has been hypothesized that the addition of systemic dose sequential chemotherapy to concurrent chemoradiotherapy, either as induction or as consolidation chemotherapy, might further improve survival rates. Recently, the Cancer and Leukemia Group B reported on a randomized phase III trial directly evaluating the addition of two cycles of carboplatin and paclitaxel to concurrent chemoradiotherapy. In this study, induction chemotherapy failed to further improve survival rates of concurrent chemoradiotherapy. A previously conducted randomized phase II study also suggested no benefit from the addition of induction chemotherapy to concomitant chemoradiotherapy. Favorable phase II data have been published supporting the use of consolidation chemotherapy. However, to date, no large randomized study evaluating a possible benefit from consolidation chemotherapy has been completed. In addition to evaluating optimal sequencing strategies of combined modality therapy, current investigations are also focusing on the integration of novel agents, including chemotherapeutic and targeted therapies. Currently ongoing trials involving novel approaches are reviewed here.Regionally advanced unresectable non -small cell lung cancer (NSCLC)-stage IIIA with bulky N 2 and stage IIIB (T 4 without pleural effusion or N 3 )-is characterized by large primary lesions and/or widespread involvement of the ipsilateral or contralateral mediastinum or supraclavicular regions (1). Eradication of bulky widespread disease poses a major therapeutic challenge, because radiation therapy alone can achieve locoregional control in only a small minority of such cases. In addition, patients are at high risk of distant failure due to initial micrometastatic spread (2 -6). Thus, an effective systemic therapeutic component needs to be incorporated into curative intent treatment plans. In the past, radiation therapy alone was considered standard therapy. However, 3-to 5-year survival rates achieved by single modality radiotherapy are <10%, and locoregional or systemic control is infrequently attained. As a result, combined modality approaches have been studied intensively, including sequential chemotherapy and radiotherapy (induction or consolidation) and concomitant chemoradiotherapy.From the experience of the last 20 years, it is clear that a sequential approach is mainly directed at eradication of micrometastatic disease. Induction chemotherapy, in particular, allows for early delivery of full systemic doses of chemotherapy and thus is a strategy best suited to eradicate micrometastatic disease (7 -9). Although it ...

High-dose radiotherapy or concurrent chemo-radiation in lung cancer patients only induces a temporary, reversible decline in QoL

“…Combined concurrent modality treatment increases long-term survival, but at the expense of a higher incidence of severe esophagitis [5][6][7][8]. In order to allow proper balancing between expected benefits and drawbacks of aggressive therapy, knowledge of the effects of a given treatment on the quality of life (QoL) is needed.…”

“…Aggressive radiotherapy or concurrent chemo-radiation therapy for lung cancer is standard care for patients with locally advanced disease, i.e. stage III non-small cell lung cancer (NSCLC) or limited stage small cell lung carcinoma (LD-SCLC) [3,4].Combined concurrent modality treatment increases long-term survival, but at the expense of a higher incidence of severe esophagitis [5][6][7][8]. In order to allow proper balancing between expected benefits and drawbacks of aggressive therapy, knowledge of the effects of a given treatment on the quality of life (QoL) is needed.…”

Chemo‐radiotherapy for advanced non‐small cell lung cancer: concurrent or sequential? It's no longer the question: a systematic review

“…50 Sequential arm, on the other hand, allows for early delivery of full systemic dose of CT and is thus suited to eradicate micrometastasis. 7 The objectives for the treatment of advanced NSCLC are palliative and include improvement of survival, symptom control, quality of life (QOL), and cost. 51 Hence, toxicity is particularly relevant, given the potential negative impact on benefit/risk ratio and QOL.…”

“…5 Unfortunately, approximately 70% of NSCLC patients are diagnosed in advanced stage of the disease (locoregionally advanced or distant metastatic disease). 3,6 Advanced NSCLC, characterized by large primary lesions and/or widespread involvement of the ipsilateral or contralateral mediastinum or supraclavicular regions, 7,8 poses a major therapeutic challenge not only due to poor response to treatment but also due to treatment related morbidities. 9 Although there is currently no official consensus on the definitive treatment of advanced NSCLC, it has been well documented that the addition of chemotherapy to radiotherapy improves survival.…”

Efficacy of triple therapies including ionising radiation, agonistic TRAIL antibodies and cisplatin

“…in case of lung cancer (1,2), rectal cancer (3), esophageal cancer (4), cancer of the anal canal (5,6) and head and neck cancer (7).…”