Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck

Hitt, Ricardo; Irigoyen, A.; Cortés, Javier; Grau, Juan J.; García-Sáenz, J.A.; Cruz-Hernández, Juan J.

doi:10.1093/annonc/mdr367

Cited by 198 publications

(165 citation statements)

References 33 publications

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“…However, this trial contained two biases: the small number of patients (only 22 were enrolled), and that they were cetuximab naïve [67]. The rationale of this recent study was confirmed by Hitt et al [68] who reported the efficacy of the addition of cetuximab to weekly paclitaxel in a phase II trial in the first-line treatment of patients with R/M-HNSCC.…”

Section: Recurrent or Metastatic Hnsccmentioning

confidence: 99%

State-of-the-Art and Emerging Treatment Options in the Management of Head and Neck Cancer: News from 2013

Denaro¹,

Russi

Adamo

et al. 2014

Oncology

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer death worldwide. Its treatment is complex and evolving. In general, early-stage disease may be managed with single-modality treatment while an advanced stage (about 60% of clinical presentation) needs a multidisciplinary approach. In this setting concurrent chemoradiation has been associated with improvement in locoregional control and organ preservation, but at the cost of significant acute and chronic toxicity. Molecular target therapies specially directed to epidermal growth factor receptor (EGFR) might improve the outcomes and reduce toxicities. In recurrent-metastatic (R/M) HNSCC, cetuximab, a monoclonal antibody against EGFR, plus platinum-based chemotherapy (CT) allow an overall survival (OS) of about 10 months. However, the prognosis for R/M-HNSCC remains dismal and additional efforts are needed. At the 2013 American Society of Clinical Oncology (ASCO) Meeting, data on induction CT, anti-EGFR inhibitors, innovative molecular targets and predictor factors were reported. Further results on target therapies were presented at the European Cancer Congress (ECC) 2013, where a large study also showed that hyperfractionated radiotherapy (RT) improve OS rates compared with standard RT. The aim of this review is to discuss current standards and emerging therapies by considering recent new updates.

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Section: Recurrent or Metastatic Hnsccmentioning

confidence: 99%

State-of-the-Art and Emerging Treatment Options in the Management of Head and Neck Cancer: News from 2013

Denaro¹,

Russi

Adamo

et al. 2014

Oncology

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“…However, cetuximab with paclitaxel combination therapy has been proven to be effective in HNSCC including several other cancers (15)(16)(17)(18)(19). For last few years the number HNSCC patients treated with PTX and cetuximab combined therapy has been increased gradually.…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel in combination with cetuximab exerts antitumor effect by suppressing NF-κB activity in human oral squamous cell carcinoma cell lines

Harada

Ferdous

Kobayashi

et al. 2014

International Journal of Oncology

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Abstract. In the present study, we examined the antitumor effect of paclitaxel (PTX) in combination with cetuximab in oral squamous cell carcinoma (OSCC) and the mechanism of its enhanced antitumor activity. Treatment of OSCC (HSC2, HSC3 and HSC4) cells with PTX (0.02 µg/ml) and cetuximab (1 µg/ml) combination resulted in a significant inhibition of cell growth in vitro compared to either agent alone. Moreover, it was found by Hoechst 33258 staining that DNA fragmentation markedly occurred in OSCC cells treated with PTX and cetuximab combination treatment. Furthermore, PTX and cetuximab combination treatment reduced the expression of p65 (NF-κB) protein in OSCC cells. In our in vivo experiment, HSC2 tumor-bearing nude mice were treated with PTX (20 mg/kg/day, twice/week, 3 weeks) and/or cetuximab (20 mg/kg/day, twice/week, 3 weeks). Tumor growth was significantly suppressed by PTX and cetuximab combined treatment when compared to PTX or cetuximab alone, or the untreated control. TUNEL-positive cells were upregulated in HSC2 tumors treated with PTX and cetuximab. In addition, immunohistochemical staining revealed that expression of p65 was downregulated in HSC2 tumors treated with PTX and cetuximab. Our results indicate that cetuximab may enhance the effect of PTX in OSCC through the downregulation of PTX induced p65 expression. Therefore, the combination of PTX and cetuximab might be a promising option for OSCC treatment. IntroductionOral squamous cell carcinoma (OSCC) is the 8th most common cancer in humans, which accounts for ~2% of all carcinomas in women and 4% in men worldwide (1,2). Over 300,000 new cases of OSCC are diagnosed annually with ~11,000 new cases in Japan (3). Surgery, chemotherapy and radiotherapy are the standards for the treatment of head and neck squamous cell carcinomas (HNSCCs) including OSCC. However, despite recent advances in cancer diagnosis, surgery, chemotherapy, radiotherapy and other treatment methods, the overall survival rate of OSCC is ~50% in the advanced stage of the disease (4,5). Almost 60% of HNSCC patients are diagnosed with locally advanced disease at presentation (6). Therefore, it is important to establish more promising therapeutic strategies.Cetuximab (Erbitux ® ; formerly IMC-C225) is a chimeric (mouse/human) IgG1 monoclonal antibody that targets the extracellular ligand-binding domain of EGFR with high affinity and inhibits tumor growth, invasion, angiogenesis and metastasis (7,8). Cetuximab causes G1 phase cell cycle arrest by decreasing cyclin-dependent kinase 2 (CDK2) and increasing p27Kip1 levels in tumor cell lines (9). Paclitaxel (PTX) is a diterpenoid isolated from the bark of the Pacific yew, Taxus brevifolia (10). PTX induces mitotic arrest and cell death by binding to microtubules, promoting microtubule assembly, and stabilizing tubulin polymers against depolymerization affecting cells in the G2/M-phase (11,12).Most of the available reports on HNSCC demonstrated the effect of cetuximab in combination with cisplatin/platinumbased drugs or radiotherapy (7,1...

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“…Common grade 3/4 adverse events were acne-like rash (24%), asthenia (17%) and neutropenia (13%). While prior chemotherapy and the development of acne-like rash were associated with tumor response but not survival, there was no association between tumor EGFR expression, or EGFR gene copy number and outcome [22].…”

Section: Taxanesmentioning

confidence: 76%

Treatment of Locally Recurrent and Metastatic Squamous Cell Carcinoma of Head & Neck

Ikpeazu¹

2016

Head Neck Cancer Res

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The survival rate at 3 years after potentially curative surgical or radiation treatment for locally advanced squamous cell carcinoma of head and neck (SCCHN) remains quite poor at 30 to 50%. Over 50% of these patients relapse locally or at distant sites and with a median survival of 6-9 months. This review focuses on the established and experimental strategies seeking to improve this outcome. Cetuximab is a chimeric immunoglobulin G1 monoclonal antibody engineered specifically to compete with the natural ligand for EGFR binding sites on the external surface of the cell membrane. This antibody have demonstrated significant disease control rate of over 45% as single agent in the locally recurrent/metastatic disease setting. The combination of cetuximab with platinum-based and taxane-based chemotherapy regimens has resulted in disease control rate of up to 80%. Studies are currently ongoing to assess the activity of immunotherapeutic agents like CTLA-4, PD-1, and PD-L1 inhibitors in the treatment of advanced SCCHN both in biomarker selected and unselected patient population with encouraging preliminary results. Moreover, the combination of these agents with standard chemotherapy regimens, and with cetuximab in the treatment of SCCHN is also being explored.

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Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck

Cited by 198 publications

References 33 publications

State-of-the-Art and Emerging Treatment Options in the Management of Head and Neck Cancer: News from 2013

State-of-the-Art and Emerging Treatment Options in the Management of Head and Neck Cancer: News from 2013

Paclitaxel in combination with cetuximab exerts antitumor effect by suppressing NF-κB activity in human oral squamous cell carcinoma cell lines

Treatment of Locally Recurrent and Metastatic Squamous Cell Carcinoma of Head & Neck

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