Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501.
ABSTRACT To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease, small-cell lung cancer (ED-SCLC).
In this phase II trial, 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m(2) and etoposide 120 mg/m(2), which was followed by bevacizumab alone until death or disease progression occurred. The primary end point was the proportion of patients alive at 6 months without disease progression (ie, progression-free survival [PFS]). Secondary end points included overall survival (OS), objective response rate, and toxicity. Correlative studies were performed to explore the relationship between baseline and changes in plasma vascular endothelial growth factor (VEGF), soluble cell adhesion molecules (ie, vascular cell adhesion molecule [VCAM], intercellular cell adhesion molecule [ICAM], and E-selectin) and basic fibroblast growth factor and outcome.
The 6-month PFS was 30.2%, the median PFS was 4.7 months, and OS was 10.9 months. The response rate was 63.5%. The most common adverse event was neutropenia (57.8%). Only one patient had grade 3 pulmonary hemorrhage. Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels. No relationships between outcome and any other biomarkers were seen.
The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls who received this chemotherapy regimen without bevacizumab. This regimen appears to be well tolerated and has minimal increase in toxicities compared with chemotherapy alone. Baseline VCAM levels predicted survival, but no other relationships among treatment, biomarkers, and outcome were identified.
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ABSTRACT: Cell adhesion is a basic count in inter- and intracellular communication and plays an important role in tumor progression. In this study, the expression of E-selectin, ICAM-1 and VCAM-1 were evaluated by means of immunohistochemistry in a group of 153 lung cancer specimens. E-selectin immunoreactivity was localized mostly on endothelial cell venules and capillaries with an average staining intensity of 75% of cells in the NSCLC, while in SCLC the intensity of the staining was 69%. The staining pattern for ICAM-1 reached an average intensity of 57%, in both NSCLC and SCLC. Finally, VCAM-1 immunoreactivity was detected only in NSCLC with an average intensity of 12% on endothelial cell venules and capillaries. This study provides a contribution towards the understanding of the basic mechanisms of cell adhesion in lung cancer progression.Anticancer research 22(6C):4039-43. · 1.73 Impact Factor
Article: Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).[show abstract] [hide abstract]
ABSTRACT: This guideline is for the management of patients with small cell lung cancer (SCLC) and is based on currently available information. As part of the guideline, an evidence-based review of the literature was commissioned that enables the reader to assess the evidence as we have attempted to put the clinical implications into perspective. We conducted a comprehensive review of the available literature and the previous American College of Chest Physicians guidelines of SCLC. Controversial and less understood areas of the management of SCLC were then subject to an exhaustive review of the literature and detail analyses. Experts in evidence-based analyses compiled the accompanying systematic review titled "Evidence for Management of SCLC." The evidence was then assessed by a panel of experts to incorporate "clinical relevance." The resultant guidelines were then scored according to the grading system outlined by the American College of Chest Physicians grading system task force. SCLC accounts for 13 to 20% of all lung cancers. Highly smoking related and initially responsive to treatment, it leads to death rapidly in 2 to 4 months without treatment. SCLC is staged as limited-stage and extensive-stage disease. Limited-stage disease is treated with curative intent with chemotherapy and radiation therapy, with approximately 20% of patients achieving a cure. For all patients with limited-stage disease, median survival is 16 to 22 months. Extensive-stage disease is primarily treated with chemotherapy with a high initial response rate of 60 to 70% but with a median survival of 10 months. All patients achieving a complete remission should be offered prophylactic cranial irradiation. Relapsed or refractory SCLC has a uniformly poor prognosis. In this section, evidence-based guidelines for the staging and treatment of SCLC are outlined. Limited-stage SCLC is treated with curative intent. Extensive-stage SCLC has high initial responses to chemotherapy but with an ultimately dismal prognosis with few survivors beyond 2 years.Chest 10/2007; 132(3 Suppl):324S-339S. · 5.25 Impact Factor