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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; Ho, Gwo Fuang; Soo, Ross A; Sundar, Raghav; Tan, Sing Huang; Yong, Wei Peng; Ow, Samuel G W; Lim, Joline S J; Chong, Wan Qin; Soe, Phyu Pyar; Tai, Bee Choo; Wang, Lingzhi; Goh, Boon Cher; Lee, Soo-Chin.
Afiliação
  • Ang YLE; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Level 7, NUHS Tower Block, 1E Kent Ridge Road, Singapore, 119228, Singapore.
  • Ho GF; University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
  • Soo RA; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Level 7, NUHS Tower Block, 1E Kent Ridge Road, Singapore, 119228, Singapore.
  • Sundar R; Cancer Science Institute, National University of Singapore, Singapore, Singapore.
  • Tan SH; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Level 7, NUHS Tower Block, 1E Kent Ridge Road, Singapore, 119228, Singapore.
  • Yong WP; The N.1 Institute for Health, National University of Singapore, Singapore, Singapore.
  • Ow SGW; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Lim JSJ; OncoCare Cancer Centre, Singapore, Singapore.
  • Chong WQ; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Level 7, NUHS Tower Block, 1E Kent Ridge Road, Singapore, 119228, Singapore.
  • Soe PP; Cancer Science Institute, National University of Singapore, Singapore, Singapore.
  • Tai BC; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Level 7, NUHS Tower Block, 1E Kent Ridge Road, Singapore, 119228, Singapore.
  • Wang L; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Goh BC; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Level 7, NUHS Tower Block, 1E Kent Ridge Road, Singapore, 119228, Singapore.
  • Lee SC; Cancer Science Institute, National University of Singapore, Singapore, Singapore.
BMC Cancer ; 20(1): 1118, 2020 Nov 17.
Article em En | MEDLINE | ID: mdl-33203399
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 11 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 (ORRCR + PR) and clinical-benefit rate (CBRCR + 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Neoplasias Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: BMC Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Singapura

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Neoplasias Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: BMC Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Singapura