Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil as palliative treatment in recurrent head and neck squamous cell carcinoma

Kushwaha, Vikas; Gupta, Seema; Husain, Nuzhat; Khan, Huma; Negi, M.P.S.; Jamal, Naseem; Ghatak, Ashim

doi:10.4161/15384047.2014.961881

Cited by 35 publications

(35 citation statements)

References 24 publications

(32 reference statements)

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“…3 Other treatment options were single agent methotrexate (MTX) or docetaxel in patients unfit for platinum, or combination therapies of platinum combined with 5FU or taxane. 4 MTX has a response rate (RR) of 10% to 25%, and a mean OS of 6 to 8 months, [5][6][7][8][9][10] while combination therapy with platinum and 5FU or taxane has RRs of 45% to 50%, but without OS benefit compared with single agent treatment, and with more toxicity. 4,8,10,11 The epidermal growth factor receptor (EGFR) has shown to be upregulated in 90% to 100% of the head and neck cancers.…”

Section: Introductionmentioning

confidence: 99%

Methotrexate plus or minus cetuximab as first‐line treatment in a recurrent or metastatic (R/M) squamous cell carcinoma population of the head and neck (SCCHN), unfit for cisplatin combination treatment, a phase Ib‐randomized phase II study Commence

Ham¹,

Meerten

Fiets

et al. 2020

Head & Neck

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Background: Methotrexate in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) has limited progression-free survival (PFS) benefit. We hypothesized that adding cetuximab to methotrexate improves PFS. Methods: In the phase-Ib-study, patients with R/M SCCHN received methotrexate and cetuximab as first-line treatment. The primary objective was feasibility. In the phase-II-study patients were randomized to this combination or methotrexate alone (2:1). The primary endpoint was PFS. Secondary endpoints were overall survival (OS), toxicity, and quality of life (QoL).

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Section: Introductionmentioning

confidence: 99%

Methotrexate plus or minus cetuximab as first‐line treatment in a recurrent or metastatic (R/M) squamous cell carcinoma population of the head and neck (SCCHN), unfit for cisplatin combination treatment, a phase Ib‐randomized phase II study Commence

Ham¹,

Meerten

Fiets

et al. 2020

Head & Neck

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“…1,2 Patients with disease progression after first-line combination chemotherapy with or without biologic therapy have poor prognoses and are typically treated with single agents (eg, methotrexate, docetaxel, or cetuximab), which yield objective response rates (ORRs) of 4% to 13%. [3][4][5][6] Agents targeting the anti-programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) pathway have shown promising activity in recurrent/metastatic (R/M) HNSCC with 2 PD-1 monoclonal antibodies (mAbs) approved for treatment of patients with platinum-refractory R/M HNSCC. [7][8][9][10] Durvalumab, a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, has also shown antitumor activity as monotherapy in R/M HNSCC.…”

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confidence: 99%

Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1–Low/Negative Recurrent or Metastatic HNSCC

et al. 2019

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IMPORTANCE Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression. OBJECTIVE To assess safety and objective response rate of durvalumab combined with tremelimumab. DESIGN, SETTING, AND PARTICIPANTS The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1-low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific. INTERVENTIONS Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy. MAIN OUTCOMES AND MEASURES Safety and tolerability and efficacy measured by objective response rate. RESULTS Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%-13.79%) in the combination arm (n = 129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively. CONCLUSIONS AND RELEVANCE In patients with R/M HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02319044

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“…Currently, a multi-model therapeutic approach is used for SCCHN including chemotherapy, radiation therapy, and surgical excision [ 3 ]. Chemotherapeutics used for head and neck cancer include the following: cisplatin, paclitaxel, carboplatin, 5-fluorouracil, mitomycin-C, cetuximab, and methotrexate [ 7 , 8 ]. Analysis of the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer Trial suggested that p16-positive oropharyngeal cancer may be more effectively treated with cisplatin than cetuximab in conjunction with radiotherapy; however, more studies are needed due to limitations of this study such as the small sample size [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of novel chemotherapeutics for feline oral squamous cell carcinoma

et al. 2018

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Feline oral squamous cell carcinomas (FOSCC) are highly aggressive neoplasms with short survival times despite multimodal treatment. FOSCC are similar to squamous cell carcinomas of the head and neck (SCCHN) in humans, which also present therapeutic challenges. The current study was undertaken to identify novel chemotherapeutics using FOSCC cell lines. A high throughput drug screen using 1,952 drugs was performed to identify chemotherapeutics for further investigation. Two of the drugs identified in the drug screen, actinomycin D and methotrexate, and two drugs with similar molecular targets to drugs found to be efficacious in the screening, dinaciclib and flavopiridol, were selected for further investigation. Drug inhibition profiles were generated for each drug and cell line using an MTS assay. In addition, the effects of the drugs of interest on cell cycle progression were analyzed via a propidium iodide DNA labeling assay. Changes in caspase-3/7 activity after treatment with each drug were also determined. The findings demonstrated effectiveness of the drugs at nanomolar concentrations with sensitivity varying across cell lines. With all of the drugs except for actinomycin D, evidence for G1 arrest was found. Dinaciclib and flavopiridol were demonstrated to induce apoptosis. The results of the study suggest that the selected drugs are potential candidates for developing novel chemotherapeutic approaches to FOSCC. Through these studies, novel therapeutic strategies for the treatment of FOSCC can be developed to provide better care for affected cats which can also serve as proof of concept studies to inform translational studies in SCCHN in humans.

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Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil as palliative treatment in recurrent head and neck squamous cell carcinoma

Cited by 35 publications

References 24 publications

Methotrexate plus or minus cetuximab as first‐line treatment in a recurrent or metastatic (R/M) squamous cell carcinoma population of the head and neck (SCCHN), unfit for cisplatin combination treatment, a phase Ib‐randomized phase II study Commence

Methotrexate plus or minus cetuximab as first‐line treatment in a recurrent or metastatic (R/M) squamous cell carcinoma population of the head and neck (SCCHN), unfit for cisplatin combination treatment, a phase Ib‐randomized phase II study Commence

Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1–Low/Negative Recurrent or Metastatic HNSCC

Investigation of novel chemotherapeutics for feline oral squamous cell carcinoma

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