BACKGROUNDSystemic treatment of metastatic melanoma is largely ineffective and alternative approaches are needed. Imatinib mesylate is an oral tyrosine kinase inhibitor that targets bcr‐Abl, c‐kit, platelet‐derived growth factor receptor (PDGFR)‐α, and PDGFR‐β, leading to remarkable clinical responses in several cancers. Signal transduction via c‐kit, PDGFR‐α, and PDGFR‐β has been demonstrated in malignant melanoma.METHODSThe primary objective of this Phase II study was to determine the response rate, response duration, and the frequency of 6‐month progression‐free survival in patients who could receive up to 2 prior therapeutic regimens. Initially, patients received imatinib at at dose of 400 mg twice orally each day. Based on Simon's optimal design, the study allowed entry of 21 patients; if there were ≥ 2 objective responses, accrual would then continue to a total of 41 patients.RESULTSTwenty‐six patients were enrolled. Patients experienced 29 episodes of Grade 3 and 2 episodes of Grade 4 toxicity (according to National Cancer Institute common toxicity criteria). No objective clinical responses were noted among the 25 evaluable patients. The median time to progression was 54 days and the median overall survival was 200 days. No patient was free of disease progression at 6 months. Paraffin‐embedded tumor specimens from 15 patients were tested for expression of imatinib responsive kinases by immunohistochemistry. Three tumors had moderate and 5 tumors had weak staining for c‐kit. Five tumor samples had weak staining for PDGFR‐α and ‐β.CONCLUSIONSImatinib is an inactive single agent in metastatic melanoma in a population of predominately pretreated patients. The levels of c‐kit and/or PDGFR‐α, ‐β expression in the current study were lower than previously reported. Alternative treatment strategies remain a priority for patients with advanced melanoma. Cancer 2006. © 2006 American Cancer Society.

No abstract

Introduction: Most patients (70%) with limited-stage SCLC (LS-SCLC) who are treated with curative-intent therapy suffer disease relapse and cancer-related death. We evaluated circulating tumor DNA (ctDNA) as a predictor of disease relapse and death after definitive therapy in patients with LS-SCLC. Methods: In our previous work, we developed a plasmabased ctDNA assay to sequence 14 genes (TP53, RB1, BRAF, KIT, NOTCH1-4, PIK3CA, PTEN, FGFR1, MYC, MYCL1, and MYCN) that are frequently mutated in SCLC. In this work, we evaluated 177 plasma samples from 23 patients with LS-SCLC who completed definitive chemoradiation (n ¼ 21) or surgical resection (n ¼ 2) and had an end-of-treatment blood collection (median 4 d, range 0-40 d from treatment completion) plus monthly surveillance blood sampling. Median overall survival (OS) and progression-free survival (PFS) were compared using a Wilcoxon test. Results: The median OS among patients in whom we ever detected ctDNA after definitive treatment (n ¼ 15) was 18.2 months compared with a median OS of greater than 48 months among patients in whom we never detected ctDNA after definitive treatment (n ¼ 8; p ¼ 0.081). The median PFS among patients in whom we ever detected ctDNA after definitive treatment was 9.1 months compared with a median PFS of greater than 48 months among patients in whom we never detected ctDNA after definitive treatment (p < 0.001). Conclusions: Detection of ctDNA in patients with LS-SCLC after curative-intent therapy predicts disease relapse and death. Prospective trials using ctDNA as an integral biomarker for therapeutic selection should be considered in SCLC.

No abstract