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A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours.


ABSTRACT: BACKGROUND:We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (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). CONCLUSIONS:The addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial. TRIAL REGISTRATION:The study was registered ( NCT01803503 ) prospectively on clinicaltrials.gov on 4th March 2013.

SUBMITTER: Ang YLE 

PROVIDER: S-EPMC7672922 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours.

Ang Yvonne L E YLE   Ho Gwo Fuang GF   Soo Ross A RA   Sundar Raghav R   Tan Sing Huang SH   Yong Wei Peng WP   Ow Samuel G W SGW   Lim Joline S J JSJ   Chong Wan Qin WQ   Soe Phyu Pyar PP   Tai Bee Choo BC   Wang Lingzhi L   Goh Boon Cher BC   Lee Soo-Chin SC  

BMC cancer 20201117 1


<h4>Background</h4>We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (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.<h4>Methods</h4>Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m<sup>2</sup>, with or without su  ...[more]

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