ONCOLOGY.
No. 10
REVIEW ARTICLE
Neoadjuvant Chemotherapy for Resectable Non–Small-Cell Lung Cancer
By Jhanelle Gray, MD1, Eric Sommers, MD2, Miguel Alvelo-Rivera, MD3, Lary Robinson, MD4,
Gerold Bepler, MD, PhD5 |
September 14, 2009
1 Assistant Professor of Medicine and Oncological Sciences, University of South Florida, Assistant Member, Thoracic Oncology
2 Assistant Professor of Surgery, University of South Florida, Assistant Member, Thoracic Oncology
3 Associate Professor of Surgery,
University of South Florida,
Associate Member,
Thoracic Oncology
4
Professor of Surgery, University of South Florida, Senior Member, Thoracic Oncology
5 Professor of Medicine and Oncological Sciences, University of South Florida, Department Chair, Thoracic Oncology
Moffitt Cancer Center & Research Institute,
Tampa, Florida
N2 Disease
Although surgery offers the best chance for survival to patients with limited-station N2 disease, not all patients with N2 disease are appropriate candidates for surgical resection. Neoadjuvant systemic chemotherapy may play a role in the management of this disease to help facilitate local surgical control. Many patients may have technically resectable disease but may not be curatively resectable. That is, they will have microscopic or macroscopic disease following their surgical procedure, solidifying their chances for relapse. For these patients, consideration must be given to concurrent chemoradiation for definitive treatment (Table 5). Although phase II studies did suggest a benefit to neoadjuvant concurrent chemoradiation therapy followed by surgery,[30-32] randomized trials found no additional benefit to surgery following bimodality induction therapy.[33-37]
Adjuvant vs Neoadjuvant Chemotherapy
Many studies have called for a randomized trial to evaluate and compare adjuvant vs neoadjuvant chemotherapy in patients with resectable cancer. In the Neoadjuvant/Adjuvant Taxol (paclitaxel) Carboplatin(Drug information on carboplatin) Hope (NATCH) trial from the Spanish Lung group, participants with stage I (> 2 cm), II, and T3, N1 NSCLC were randomized to either neoadjuvant or adjuvant carboplatin/paclitaxel and surgery. The preliminary results from the neoadjuvant arm, which was presented at the 2007 ASCO meeting,[38] found neoadjuvant chemotherapy to be safe and feasible.
Final results of the NATCH trial were presented in August 2009 at the 13th World Congress on Lung Cancer, organized by the International Association for the Study of Lung Cancer (IASLC).[39] Among the 624 participants in the study at the time of presentation, no significant difference in progression-free or overall survival was detected. With preoperative chemotherapy, adjuvant chemotherapy, and surgery alone, the 5-year progression-free survival rates were 38.3%, 36.6%, and 34%, and the 5-year overall survival rates were 46.6%, 45.5%, and 44%, respectively. This study was limited by the fact that a majority of participants had stage IA/IB NSCLC. Moreover, many participants in the adjuvant chemotherapy arm were unable to receive the planned three cycles of chemotherapy due to peri/postoperative morbidity. Both of these factors may have contributed to the difficulty in achieving statistical significance. Nevertheless, subset and exploratory analyses of the trial are currently underway to evaluate prognostic factors as well as prognostic and predictive molecular markers.
The Chinese Society of Lung Cancer has launched the Survival Study of Docetaxel(Drug information on docetaxel) and Carboplatin as Neoadjuvant vs Adjuvant Chemotherapy in Early-Stage NSCLC (NCT00321334). This investigation is set to enroll 410 participants and to be completed in March 2012. The trial may provide long-awaited answers to some key questions.
A systematic review of 31 randomized trials (21 postoperative and 10 preoperative chemotherapy) with over 10,000 subjects presented at ASCO 2008 is available. In this review, no differences in surgical morbidity/mortality, disease-free survival, or overall survival were found between the two groups.[40] Based on these results, it would appear that the timing of chemotherapy administration has little impact on outcomes for patients with operable NSCLC.
Future Directions
To determine which chemotherapy regimens are ideal for which patient, molecular analysis is currently being studied in the metastatic and adjuvant setting. Molecular analysis for classification of NSCLC will play a key role as a tool for therapy-related decisions.
Conclusions
Lung cancer carries a poor prognosis. In efforts to improve that prognosis, the role of neoadjuvant chemotherapy has been studied extensively. From the type of surgical procedure performed to the type of chemotherapy used—not only within but also between studies—the data are difficult to analyze because of multiple heterogeneities. Nevertheless, potential advantages of neoadjuvant chemotherapy can be hypothesized. These include a decrease in tumor volume to improve curative surgical resection rates. With systemic administration of chemotherapy, micrometastatic disease is attended to earlier. In addition, there has been some argument for increased compliance with systemic administration of chemotherapy in the neoadjuvant setting. Whether these approaches translate into outcomes superior to those found when platinum-based chemotherapy is used in the adjuvant setting remains unknown.
Evidence about the role of neoadjuvant chemotherapy is inconclusive, as no large randomized trials comparing neoadjuvant chemotherapy to adjuvant chemotherapy in resectable NSCLC have determined any significant differences. The authors of this review believe that each patient needs to be evaluated individually by a multidisciplinary team of physicians.
Neoadjuvant chemotherapy may be beneficial to some patients, especially those who may otherwise have been unresectable. Patients must undergo adequate staging of the mediastinum via modalities such as mediastinoscopy and PET/CT. In addition to staging, the treating physician must pay close attention to the patients’ performance status, age, weight, and comorbidities when making these decisions. Finally, the addition of PORT to the treatment algorithms of patients with stage IIIA disease can be considered.
Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
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