A phase I/II study of bexarotene with carboplatin and weekly paclitaxel for the treatment of patients with advanced non-small cell lung cancer
| Autor: | James R. Rigas, Cynthia K. Hahn, Peter E. Kebbekus, Jeremy D. Whyman, Sarah F. Kokko, Sunil Bhatt, Konstantin H. Dragnev |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Oncology medicine.medical_specialty medicine.medical_treatment Neutropenia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Technical Note medicine Lung cancer Bexarotene Chemotherapy business.industry medicine.disease Carboplatin Log-rank test Regimen 030104 developmental biology chemistry Tolerability business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Thoracic Disease. 10:5531-5537 |
| ISSN: | 2077-6624 2072-1439 |
| DOI: | 10.21037/jtd.2018.09.10 |
| Popis: | Background: Rexinoids demonstrate anti-proliferative differentiation-inducing activity in multiple cancer types, including NSCLC. Prior studies have shown promising results when combining rexinoids with chemotherapy. This phase I/II study evaluates the tolerability and activity of a rexinoid, bexarotene, combined with weekly paclitaxel and monthly carboplatin. Methods: Patients with confirmed advanced stage IIIB or IV NSCLC and adequate organ function were enrolled. They were scheduled to receive carboplatin (AUC =6) and 3 doses of weekly paclitaxel (100 mg/m 2 ) every 4 weeks. Oral bexarotene was administered daily at two doses: 300 and 400 mg/m 2 /day. Results: Thirty-three patients were enrolled. Fourteen received 300 mg/m 2 /day and 19 received 400 mg/m 2 /day of bexarotene. Hematologic toxicity included grade 3 neutropenia in 7 patients. Hyperlipidemia was a major non-hematologic toxicity which was medically managed. The recommended phase II dose of bexarotene was 400 mg/m 2 /day. Response rate was 35%. Median overall survival (OS) for all patients was 8.3 months with 1-year survival of 43%. Median OS for the 300 mg/m 2 dose of bexarotene was 6.6 versus 9.8 months for the 400 mg/m 2 dose (HR, 0.73; Log rank P=0.37). Patients who experienced hypertriglyceridemia had a median OS of 9.8 months compared to 4.9 months for those who did not (HR, 0.69; Log rank P=0.33). Conclusions: The 43% 1-year survival for patients receiving bexarotene with weekly paclitaxel and monthly carboplatin is encouraging. With the availability of new classes of agents for lung cancer, further evaluation of this regimen in unselected patients is not warranted. Our study confirms prior subgroup analyses showing a significant correlation between bexarotene-induced hypertriglyceridemia and survival. Further research is needed to identify molecular biomarkers to identify this subset of patients and to explore rexinoids in other combinations, especially with immunotherapy. |
| Databáze: | OpenAIRE |
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