A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid t
- PDF / 1,352,721 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 91 Downloads / 170 Views
RESEARCH ARTICLE
Open Access
A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours Yvonne L. E. Ang1, Gwo Fuang Ho2, Ross A. Soo1,3, Raghav Sundar1,4,5, Sing Huang Tan6, Wei Peng Yong1,3, Samuel G. W. Ow1,5, Joline S. J. Lim1,3, Wan Qin Chong1, Phyu Pyar Soe1, Bee Choo Tai7, Lingzhi Wang3,5, Boon Cher Goh1,3,5 and Soo-Chin Lee1,3,5*
Abstract Background: We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicincyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC. Methods: Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS). Results: We enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers. There was no difference in ORR (30.3% vs 28.6%, p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38–3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%, p = 0.027 OR 0.37, 95% CI 0.14–1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15–3.48, p = 0.014) overall, as well as in breast (4.2 vs 5.6 months, p = 0.048) and other cancers (2.0 vs 5.3 months, p = 0.009), but not in lung cancers (2.9 vs 4.1 months, p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51–1.67, p = 0.789), and in the breast (18.9 vs 25.8 months, p = 0.354), lung (7.0 vs 6.7 months, p = 0.970) and other cancers (4.5 vs 8.8 months, p = 0.449) subgroups. Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%, p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%, p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%, p = 0.792). (Continued on next page)
* Correspondence: [email protected] 1 Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Level 7, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore 3 Cancer Science Institute, National University of Singapore, Singapore, Singapore Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre
Data Loading...
