Cisplatinum and Bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial

Morton, Randall P.; Rugman, F. P.; Dorman, E. B.; Stoney, Peter; Wilson, J. A.; McCormick, M; Veevers, A.; Stell, P. M.

doi:10.1007/bf00263902

Cited by 133 publications

(47 citation statements)

References 10 publications

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“…Chemotherapy (generally in combination with radiation therapy) is the standard approach for the treatment of patients with recurrent and/or metastatic HNSCC and, more recently, for patients with advanced locoregional disease. The benefits of cisplatin were shown f20 years ago (35) and this remains a common agent either alone or in combination with other chemotherapy drugs. EGFRvIII has been reported to confer resistance to cisplatin in glioma cells (36).…”

Section: Resultsmentioning

confidence: 99%

Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting

Sok

Coppelli

Thomas

et al. 2006

Clinical Cancer Research

438

364

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Purpose: Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinoma (HNSCC) where expression levels correlate with decreased survival. Therapies that block EGFR have shown limited efficacy in clinical trials and primarily when combined with standard therapy. The most common form of mutant EGFR (EGFRvIII) has been described in several cancers, chiefly glioblastoma.The present study was undertaken to determine the incidence of EGFRvIII expression in HNSCC and the biological consequences of EGFRvIII on tumor growth in response to EGFR targeting. Experimental Design: Thirty-three HNSCC tumors were evaluated by immunostaining and reverse transcription-PCR for EGFRvIII expression. A representative HNSCC cell line was stably transfected with an EGFRvIII expression construct. EGFRvIII-expressing cells and vectortransfected controls were compared for growth rates in vitro and in vivo as well as chemotherapyinduced apoptosis and the consequences of EGFR inhibition using the chimeric monoclonal antibody C225/cetuximab/Erbitux. Results: EGFRvIII expression was detected in 42 % of HNSCC tumors where EGFRvIII was always found in conjunction with wild-type EGFR. HNSCC cells expressing EGFRvIII showed increased proliferation in vitro and increased tumor volumes in vivo compared with vector-transfected controls. Furthermore, EGFRvIII-transfected HNSCC cells showed decreased apoptosis in response to cisplatin and decreased growth inhibition following treatment with C225 compared with vector-transfected control cells. Conclusions: EGFRvIII is expressed in HNSCC where it contributes to enhanced growth and resistance to targeting wild-type EGFR. The antitumor efficacy of EGFR targeting strategies may be enhanced by the addition of EGFRvIII-specific blockade.

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Section: Resultsmentioning

confidence: 99%

Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting

Sok

Coppelli

Thomas

et al. 2006

Clinical Cancer Research

438

364

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“…In certain leukaemias treated by chemotherapy, the aneuploid tumours are the most responsive (Barlogie et al, 1987). In order to test this hypothesis on solid tumours we have assessed the effect of ploidy in cancers from patients entered into two phase III prospective randomised trials of chemotherapy for end stage squamous carcinoma of the head and neck (Morton et al, 1985;Allison et al, 1989).…”

mentioning

confidence: 99%

Ploidy as a prognostic indicator in end stage squamous cell carcinoma of the head and neck region treated with cisplatinum

Cooke

Cooke²,

Bootz³

et al. 1990

Br J Cancer

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Summary We measured tumour cellular DNA in 102 patients entered into two phase III trials of chemotherapy for end stage squamous carcinoma of the head and neck. The median survival of untreated patients with aneuploid tumours was 55 days compared with 224 days for patients treated with cisplatinum. This difference was highly significant. In contrast the median survival of untreated patients with diploid tumours was 74 days compared with 118 days for treated patients. Although this difference is statistically significant, the increased survival of 6 weeks is of no clinical benefit compared with the prolongation of survival of 6 months in patients with aneuploid tumours. Multivariate analysis showed that the significant predictors of survival were Karnofsky status, response to chemotherapy and ploidy.

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“…Although the field is evolving with the development of immunotherapies and targeted therapies, we assert that regimens such as TPC could be considered instead of the EXTREME regimens in future development of definitive trials likely to involve combinations of immunotherapy and chemotherapy in this patient population [1], [2], [3], [4], [5], [6], [7], [8]. …”

Section: Discussionmentioning

confidence: 99%

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck

et al. 2018

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Lessons Learned. Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck need not be known for extreme toxicity.The weekly regimen studied here has been demonstrated to be tolerable and effective.Background.The objective of this study was to establish the response rate, progression‐free survival (PFS) and overall survival (OS), and safety profile of weekly docetaxel, platinum, and cetuximab (TPC) in patients with relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN).Materials and Methods.Twenty‐nine patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group (ECOG) performance status <3 were enrolled in an institutional review board‐approved phase II trial. This study permitted prior chemoradiation, radiation, and/or surgery, provided that 3 months had elapsed since the end of the potentially curative treatment. Patients received cisplatin 30 mg/m2 or carboplatin area under the curve (AUC) 2, docetaxel 30 mg/m2, and cetuximab 250 mg/m2 weekly for 3 weeks, followed by a break during the fourth week, for a 28‐day cycle. Planned intrapatient dose modifications were based on individual toxicity.Results.Twenty‐seven patients received TPC and were evaluable for response and toxicity. Rates of complete response (CR), partial response (PR), and confirmed PR were 3%, 52%, and 30%, respectively. The overall objective response rate was 56%. Estimated median PFS and OS were 4.8 and 14.7 months, respectively. The rates of grade 3 and 4 worst‐grade adverse events (AEs) per patient were 85% and 7%, respectively. Dose density through cycle 4 was preserved for all patients; however, treatment beyond cycle 6 with the TPC regimen proved unfeasible.Conclusion.Weekly docetaxel, cisplatin, and cetuximab is an effective regimen for patients with metastatic or recurrent SCCHN. Response rates, PFS, and OS compare favorably with other combination chemotherapy treatments. Grade 4 toxicity rates observed in this study were substantially lower than those described with regimens using less frequent, higher‐dose chemotherapy schedules.

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Cisplatinum and Bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial

Cited by 133 publications

References 10 publications

Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting

Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting

Ploidy as a prognostic indicator in end stage squamous cell carcinoma of the head and neck region treated with cisplatinum

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck

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