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      A Human Head and Neck Squamous Cell Carcinoma Cell Line with Acquired cis-Diamminedichloroplatinum-Resistance Shows Remarkable Upregulation of BRCA1 and Hypersensitivity to Taxane

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          Abstract

          Recently, an inverse relationship between resistance to platinum-based chemotherapeutic agents and taxanes has been implicated in breast and ovarian cancers, and a possible pivotal role for BRCA1 has also been suggested. Because cis-diamminedichloroplatinum (CDDP) and taxanes are the most active antitumor agents against head and neck squamous cell carcinoma (HNSCC), we analyzed the sensitivity of nine HNSCC cell lines and their previously established derived CDDP-resistant cell lines to two representative taxanes: docetaxel and paclitaxel. None of the nine original cell lines showed any cross resistance between CDDP and taxanes, but one of the CDDP-resistant cell lines, RPMI2650CR, demonstrated hypersensitivity to both taxanes when compared to the parental cell line, RPMI2650. Furthermore, RPMI2650CR exhibited increased expression of BRCA1. These data suggest that (i) taxanes are a good candidate for a second-line therapeutic drug for HNSCC patients with acquired CDDP resistance and (ii) BRCA1 can be a candidate marker for predicting an inverse CDDP/taxane sensitivity phenotype in HNSCC.

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          Most cited references 8

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          The resurgence of platinum-based cancer chemotherapy.

           Lloyd Kelland (2007)
          The accidental discovery of the anticancer properties of cisplatin and its clinical introduction in the 1970s represent a major landmark in the history of successful anticancer drugs. Although carboplatin--a second-generation analogue that is safer but shows a similar spectrum of activity to cisplatin--was introduced in the 1980s, the pace of further improvements slowed for many years. However, in the past several years interest in platinum drugs has increased. Key developments include the elucidation of mechanisms of tumour resistance to these drugs, the introduction of new platinum-based agents (oxaliplatin, satraplatin and picoplatin), and clinical combination studies using platinum drugs with resistance modulators or new molecularly targeted drugs.
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            Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer.

             ,  Jacques Bernier,  Felix Rey (2007)
            Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease. We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival. A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group. As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
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              Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer.

              A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy. We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival. With a minimum of 2 years of follow-up (> or =3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There was better locoregional control in the TPF group than in the PF group (P=0.04), but the incidence of distant metastases in the two groups did not differ significantly (P=0.14). Rates of neutropenia and febrile neutropenia were higher in the TPF group; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group. Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. (ClinicalTrials.gov number, NCT00273546 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
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                Author and article information

                Journal
                Int J Otolaryngol
                IJOL
                International Journal of Otolaryngology
                Hindawi Publishing Corporation
                1687-9201
                1687-921X
                2011
                20 October 2011
                : 2011
                Affiliations
                1Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan
                2Department of Otolaryngology-Head and Neck Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan
                3Department of Digestive Tract Surgery and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan
                Author notes

                Academic Editor: Leonard P. Rybak

                Article
                10.1155/2011/521852
                3199181
                22046189
                Copyright © 2011 Yuriko Saiki et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research Article

                Otolaryngology

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