A Randomized Phase II Study of Linsitinib (OSI-906) Versus Topotecan in Patients With Relapsed Small-Cell Lung Cancer
Autor: | Alberto Chiappori, Taher Abu Hejleh, Jorge Nieva, Christine L. Hann, Michael J. Schell, Taofeek K. Owonikoko, Anne M. Traynor, Afshin Dowlati, Xiuhua Zhao, Leora Horn, Gregory A. Otterson, Daniel M. Sullivan, Helen J. Ross |
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Rok vydání: | 2016 |
Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Linsitinib Lung Neoplasms medicine.drug_class Phases of clinical research Neutropenia Pharmacology Gastroenterology Tyrosine-kinase inhibitor Receptor IGF Type 1 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Humans Lung cancer Aged Aged 80 and over Leukopenia Performance status business.industry Clinical Trial Results Imidazoles Middle Aged medicine.disease Small Cell Lung Carcinoma 030104 developmental biology Oncology chemistry Pyrazines 030220 oncology & carcinogenesis Female Topotecan Neoplasm Recurrence Local medicine.symptom business medicine.drug |
Zdroj: | The Oncologist |
ISSN: | 1549-490X 1083-7159 |
Popis: | Lessons Learned Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials. Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC. Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients. Background. Treatment of relapsed small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1 receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially may be active against SCLC. Methods. In this phase II study, 8 eligible patients were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or 2.3 mg/m2 orally, daily for 5 days for 4 cycles) or linsitinib (150 mg orally twice daily until progression). The primary endpoint was progression-free survival. Patients with relapsed SCLC, platinum sensitive or resistant, performance status (PS) 0–2, and adequate hematologic, renal, and hepatic function were enrolled. Patients with diabetes, cirrhosis, and those taking insulinotropic agents were excluded. Crossover to linsitinib was allowed at progression. Results. Fifteen patients received topotecan (8 resistant, 3 with PS 2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29 with linsitinib achieved stable disease. Median progression-free survival was 3.0 (95% confidence interval [CI], 1.5–3.6) and 1.2 (95% CI, 1.1–1.4) months for topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95% CI, 2.2–7.6) and 3.4 (95% CI, 1.8–5.6) months for topotecan and linsitinib, respectively (p = .71). Grade 3/4 adverse events (>5% incidence) included anemia, thrombocytopenia, neutropenia/leukopenia, diarrhea, fatigue, dehydration, and hypokalemia for topotecan; and thrombocytopenia, fatigue, and alanine aminotransferase/aspartate aminotransferase elevations for linsitinib. Conclusion. Linsitinib was safe but showed no clinical activity in unselected, relapsed SCLC patients. |
Databáze: | OpenAIRE |
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