Adjuvant Paclitaxel Plus Carboplatin Compared With Observation in Stage IB Non-Small-Cell Lung Cancer: CALGB 9633 With the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups

Duke University, Durham, North Carolina, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 09/2008; 26(31):5043-51. DOI: 10.1200/JCO.2008.16.4855
Source: PubMed


Adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC) is now accepted on the basis of several randomized clinical trials (RCTs) that demonstrated improved survival. Although there is strong evidence that adjuvant chemotherapy is effective in stages II and IIIA NSCLC, its utility in stage IB disease is unclear. This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC.
Within 4 to 8 weeks of resection, patients were randomly assigned to adjuvant chemotherapy or observation. Eligible patients had pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy. Chemotherapy consisted of paclitaxel 200 mg/m(2) intravenously over 3 hours and carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously over 45 to 60 minutes every 3 weeks for four cycles. The primary end point was overall survival.
Three hundred-forty-four patients were randomly assigned. Median follow-up was 74 months. Groups were well-balanced with regard to demographics, histology, and extent of surgery. Grades 3 to 4 neutropenia were the predominant toxicity; there were no treatment-related deaths. Survival was not significantly different (hazard ratio [HR], 0.83; CI, 0.64 to 1.08; P = .12). However, exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors > or = 4 cm in diameter (HR, 0.69; CI, 0.48 to 0.99; P = .043).
Because a significant survival advantage was not observed across the entire cohort, adjuvant chemotherapy should not be considered standard care in stage IB NSCLC. Given the magnitude of observed survival differences, CALGB 9633 was underpowered to detect small but clinically meaningful improvements. A statistically significant survival advantage for patients who had tumors > or = 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors.

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    • "Similarly, as seen in the IALT discussed above, in CALGB 9633 the benefit of adjuvant faded with time and emphasised the need for prolonged follow-up to establish the proof of benefit in adjuvant setting. Interestingly enough, a subgroup exploratory analysis was performed in CALGB 9633 according to tumour size P or <4 cm [8]. In the updated analysis with a 74 month followup the overall survival in stage IB was not improved in the intent-to-treat population, but an overall survival benefit was seen for patients with a tumour P4 cm with an HR of death = 0.69 and a P value = 0.043, a median overall survival of 99 months compared with 77 months in the surgery only arm. "

    EJC Supplements 09/2013; 11(2):131–136. DOI:10.1016/j.ejcsup.2013.07.024 · 9.39 Impact Factor
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    • "Many randomized clinical trials have reported the efficacy of platinum-based adjuvant chemotherapy after surgical resection in stage II–IIIA lung cancer [5-7]. The efficacy of platinum-based adjuvant chemotherapy in stage IB NSCLC also has been studied in a clinical trial [8] but the final results did not demonstrate clear benefits of adjuvant chemotherapy. Adjuvant chemotherapy is not currently a standard treatment for stage IB NSCLC and its role in stage IB disease remains controversial. "
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    ABSTRACT: Background Although overall survival for non-small cell lung cancer (NSCLC) has increased, survival rate for pathologically staged T2aN0M0 stage IB NSCLC remains low. Adjuvant chemotherapy is not a standard treatment for stage IB NSCLC. Our purpose was to determine the efficacy of platinum-based adjuvant chemotherapy in stage IB NSCLC. Methods We retrospectively reviewed the medical records of 119 stage IB patients who underwent lobectomy and mediastinal lymph node dissection. Among these, 60 patients underwent platinum-based adjuvant chemotherapy (adjuvant group) and 59 did not receive chemotherapy (observation group). Results Participants had a mean age of 62.12 ± 11.51 years and 73 (61.3%) were male. The median follow-up period was 49.04 months. Mean age was higher in the observation group whereas patients in the adjuvant group had larger tumors, more dissected lymph nodes, and better performance status. The 5-year overall survival was 64.7% in the observation group and 88.2% in the adjuvant group (p = 0.010). The 5-year disease-free survival was 51.3% in the observation group and 74.0% in the adjuvant group (p = 0.011). In multivariate analysis, only platinum-based adjuvant chemotherapy was a risk factor for overall survival [hazard ratio (HR) = 0.428, p = 0.049] and disease-free survival (HR = 0.57, p = 0.043). In subset analysis, patients with a larger tumor (greater than 3.2 cm), moderate to poor differentiation, and good performance status (Eastern Cooperative Oncology Group, 0) benefitted from platinum-based adjuvant chemotherapy. Conclusions Platinum-based adjuvant chemotherapy for surgically treated stage IB NSCLC might offer better survival than observation alone. A large-scale randomized clinical trial is needed to validate these findings.
    Journal of Cardiothoracic Surgery 06/2013; 8(1):151. DOI:10.1186/1749-8090-8-151 · 1.03 Impact Factor
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    • "There is increasing evidence to support the role of postoperative adjuvant chemotherapy in locally advanced-stage lung cancer. However, the effect of adjuvant chemotherapy in early-stage adenocarcinoma remains to be determined [34]. In the study we analyzed the predictive ability of the number of EMT-related proteins’ alteration in patients with early-stage lung adenocarcinoma. "
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers. The aim was to evaluate that whether EMT-related proteins' alterations are associated with clinicopathological features and prognosis in lung adenocarcinoma. The expression of EMT-related proteins including cytokeratin, E-cadherin, TTF-1, β-catenin, vimentin, Snail, Twist, CD44 was evaluated by immunohistochemistry using a tissue array method in the lung adenocarcinoma tissues of 95 patients. In addition, clinicopathological characteristics and survival were compared with the expression of EMT-related proteins. Loss of epithelial proteins and/or acquisition of the expression of mesenchymal proteins were observed in lung adenocarcinoma. These proteins’ alteration was associated with poor cell differentiation and poor patients’ outcome, respectively. Subjects were divided into two groups according to the number of EMT-related proteins’ alteration. A higher number of EMT-related proteins’ alteration was found to be significantly associated with unfavorable outcome. Multivariate analysis showed that a higher number of EMT-related proteins’ alteration was independently associated with poor prognosis. The number of EMT-related proteins’ alteration is a significant prognostic marker to predict overall survival in patients with lung adenocarcinoma. The information generated will be valuable for the prognosis of patients with lung adenocarcinoma. Virtual slides The virtual slides for this article can be found here:
    Diagnostic Pathology 05/2013; 8(1):89. DOI:10.1186/1746-1596-8-89 · 2.60 Impact Factor
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