Adjuvant Therapy in Non-Small Cell Lung Cancer: Current and Future Directions

Abstract

The cornerstone of treatment for early-stage non-small cell lung cancer (NSCLC) has long been surgical resection. Over the past few years, there has been a paradigm shift to provide adjuvant platinum-based chemotherapy for patients with completely resected stage II-IIIA NSCLC founded on large randomized clinical trials demonstrating longer overall survival with this treatment. Reassuringly, the National Cancer Institute of Canada Cancer Therapeutics Group JBR.10 trial recently reported a continued survival advantage for patients treated with adjuvant chemotherapy after >9 years of median follow-up. In contrast, the gains from using this approach for stage IB disease are less clear, although data from an unplanned subgroup analysis suggest benefit for patients with tumors >4 cm. Herein, we review the evidence supporting adjuvant therapy in early-stage NSCLC patients before discussing key mitigating factors in providing treatment, such as stage of disease and the impact of the new seventh edition of the tumor-node-metastasis classification system. Criteria such as patient age and performance status, as well as the value of appropriate chemotherapy selection, are highlighted as measures to help guide management. The role of postoperative radiotherapy and the future landscape of early-stage NSCLC research are also explored; namely, therapeutic strategies exploiting pharmacogenomic and gene-expression profiling, in an attempt to personalize care, and the integration of novel targeted therapies into adjuvant clinical trials. The Oncologist 2010;15:862-872

Prognostic Factors for Lymph Node Negative Stage I and IIA Non-small Cell Lung Cancer: Multicenter Experiences

“…The overall rate of grade 3 or 4 toxicity was 66% predominantly as a result of neutropenia in LACE metaanalysis (Sangha et al, 2010). We detected grade 3-4 toxicities in 52 patients (38.5%) which smaller than the literature.…”

“…Even patients are diagnosed in early stage, recurrence rates are high (Kelsey et al, 2009). 5-year OS rates are 73-25% for stage IA through stage IIIA (Sangha et al, 2010). Cisplatin based adjuvant chemotherapy can reduce the recurrence risk but there is no consensus in decision of adjuvant chemotherapy in lymph node negative early stage I and IIA NSCLC patients.…”

High Expression of Dihydropyrimidine Dehydrogenase in Lung Adenocarcinoma is Associated With Mutations in Epidermal Growth Factor Receptor: Implications for the Treatment of Non–Small-Cell Lung Cancer Using 5-Fluorouracil

“…[1][2] At the same time, the use of anti-metabolite drugs, such as the fluoropyrimidine anticancer agent 5-fluorouracil (5-FU), is an additional option for NSCLC therapy.…”

Withaferin a synergistically enhances the effects of paclitaxel against lung cancer.

“…Today, the therapeutic options and clinical outcomes of lung cancer treatment are highly dependent on the stage of the disease at the time of diagnosis [6,13,18]. Initially, a proper and accurate diagnosis is done to consider the size and location of the primary tumor, as well as the presence of regional and/or distant metastases.…”

“…Among these patients, the primary tumor is already spread beyond the lung tissue into lymph nodes (stage III) and sometimes with distant metastases (stage IV). Very frequently, advanced lung cancer patients also have undetected systemic micrometastases that can result in tumor relapse [13,18,22]. Therefore, the main clinical goal of treatment in advanced lung cancer is palliation of symptoms and to prolong the life of patients.…”