Tumor Cavitation: Impact on Objective Response Evaluation in Trials of Angiogenesis Inhibitors in Non–Small-Cell Lung Cancer
- 20 January 2009
- journal article
- thoracic oncology
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 27 (3), 404-410
- https://doi.org/10.1200/jco.2008.16.2545
Abstract
Purpose: We have observed cavitation of lesions in clinical trials of an angiogenesis inhibitor combined with chemotherapy for non–small-cell lung cancer (NSCLC). We hypothesized that cavitation might alter response assessment in such clinical trials. Patients and Methods: We performed a retrospective radiologic review of patients with NSCLC enrolled onto three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials of platinum-based chemotherapy with or without a small-molecule angiogenesis inhibitor (vascular endothelial growth factor receptor inhibitor [VEGFRI]). Response was assessed both by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and a novel alternate method in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. Rates of cavitation were documented. Results: Marked cavitation of pulmonary lesions was seen in 24% of 33 patients treated with VEGFRI combined with platinum-based chemotherapy but in none of 18 patients treated with platinum-based chemotherapy alone. Use of the alternate method for response assessment resulted in an alteration of response assessment, time to best response, duration of response, and time of disease progression in a minority of patients compared with RECIST. Conclusion: Cavitation of target and nontarget lesions is common in NSCLC patients treated with VEGFRIs and platinum-based chemotherapy. Impact on response and time to event outcomes occurred but seems to be less common. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions, potentially altering outcomes of key efficacy parameters in clinical trials. This should be prospectively assessed in clinical trials of angiogenesis inhibitors.Keywords
This publication has 30 references indexed in Scilit:
- Tumor Cavitation During Therapy with Antiangiogenesis Agents in Patients with Lung CancerJournal of Thoracic Oncology, 2008
- Acute pharmacodynamic and antivascular effects of the vascular endothelial growth factor signaling inhibitor AZD2171 in Calu-6 human lung tumor xenograftsMolecular Cancer Therapeutics, 2007
- Phase I Clinical Study of AZD2171, an Oral Vascular Endothelial Growth Factor Signaling Inhibitor, in Patients With Advanced Solid TumorsJournal of Clinical Oncology, 2007
- We Should Desist Using RECIST, at Least in GISTJournal of Clinical Oncology, 2007
- Phase I dose escalation and pharmacokinetic study of AZD2171, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinase, in patients with hormone refractory prostate cancer (HRPC)Investigational New Drugs, 2007
- Cancer Statistics, 2007CA: A Cancer Journal for Clinicians, 2007
- Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancerLung Cancer, 2006
- Randomized Phase III Study of Matrix Metalloproteinase Inhibitor BMS-275291 in Combination With Paclitaxel and Carboplatin in Advanced Non-Small-Cell Lung Cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18Journal of Clinical Oncology, 2005
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000
- The Hallmarks of CancerCell, 2000