Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: A phase II, randomized, double-blind, placebo-controlled study

Grégoire, Vincent; Hamoir, Marc; Chen, Changhu; Kane, Madeleine A.; Kawecki, Andrzej; Julka, Pramod Kumar; Wang, Hung‐Ming; Prasad, S.; D’Cruz, Anil; Radošević-Jelić, Ljiljana; Kumar, Rejnish; Korzeniowski, S; Fijuth, Jacek; Machiels, Jean‐Pascal; Sellers, Mark; Tchakov, Ilian; Raben, David

doi:10.1016/j.radonc.2011.07.008

Cited by 48 publications

(23 citation statements)

References 31 publications

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“…Hainsworth and colleagues showed no superiority of adding gefitinib to chemoradiation (25). In a large but complex randomized phase II design, the addition of gefitinib with concomitant chemoradiotherapy AE maintenance did not improve 2-year LRC either (26). In the current study, we observed good compliance rates to overall treatment with no excess of toxicity (16) but no benefit of gefitinib in the overall population.…”

Section: Discussioncontrasting

confidence: 42%

Contrasted Outcomes to Gefitinib on Tumoral IGF1R Expression in Head and Neck Cancer Patients Receiving Postoperative Chemoradiation (GORTEC Trial 2004-02)

Thariat

Bensadoun

Étienne-Grimaldi

et al. 2012

Clinical Cancer Research

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Purpose: Intermediate/high-risk operated patients with head and neck cancer may benefit from the addition of EGF receptor (EGFR) inhibitor gefitinib to chemoradiation. This study was designed to assess improved outcomes and identify predictive biomarkers.Experimental Design: Patients provided informed consent for tumor biomarker analyses and, when eligible, were further enrolled in the therapeutic CARISSA multicenter randomized phase II trial of postoperative irradiation with cisplatin þ gefitinib (GORTEC 2004-02-NCT00169221).Results: Seventy-nine patients were included in the biomarker study, whereas 27 did not meet prerequisites for randomization between gefitinib and placebo. Two-year disease-free survival (DFS) rate was 65.0% and did not differ between randomized patients treated with gefitinib or placebo (P ¼ 0.85). The similarity of DFS curves between nonrandomized patients (n ¼ 27), randomized patients without gefitinib (n ¼ 27), and randomized patients receiving gefitinib (n ¼ 25), and similar histoclinical parameter distributions for all groups, allowed us to conduct statistical analyses on the entire population. On multivariate analysis, elevated expression of PAK1 by Western blotting, CD31 and membranous insulin-like growth factor 1 receptor (IGF1R) both by immunohistochemistry was significantly associated with shorter DFS. There was a significant interaction between IGF1R and gefitinib. Gefitinib abolished the prognostic discriminative power of high IGF1R expression; patients with elevated IGF1R expression benefited from gefitinib whereas those with low IGF1R fared worse.Conclusion: Gefitinib treatment affords no significant clinical benefit on DFS in an unselected population of patients with head and neck cancer. Our results point to the potential advantage of personalizing treatment for gefitinib based on tumoral IGF1R expression. This should foster confirmatory analyses in trials involving EGFR-targeting agents.

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Section: Discussioncontrasting

confidence: 42%

Contrasted Outcomes to Gefitinib on Tumoral IGF1R Expression in Head and Neck Cancer Patients Receiving Postoperative Chemoradiation (GORTEC Trial 2004-02)

Thariat

Bensadoun

Étienne-Grimaldi

et al. 2012

Clinical Cancer Research

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“…Another gefitinib study is the study of Gregoire et al (10) study, which is phase 2 and double blind. This study is also planned as two phases.…”

Section: Place In Concomitant Use With Anti-egfr Radiotherapy In Locamentioning

confidence: 99%

Place in Concomitant Use with Anti-EGFR Radiotherapy in Locally Advanced Head and Neck Cancer Treatment

Dağdelen¹,

Ürün²

2018

meandros

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“…The study was structured in two phases: a concomitant phase (gefitinib or placebo with chemoradiation) and a maintenance phase (gefitinib or placebo alone). The investigators concluded that treatment with gefitinib did not improve 2-year loco-regional control compared to placebo, neither when given concomitantly with chemoradiation nor as maintenance therapy [37]. Another phase II study investigated the feasibility of administering gefitinib in concomitance with chemoradiation and then alone as maintenance therapy for two years.…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Radiotherapy plus EGFR inhibitors: synergistic modalities

Bossi

Platini

2017

Cancers Head Neck

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Locally advanced (stage III or IV) squamous cell carcinoma of the head and neck (SCCHN) often requires multimodal treatment, consisting of a combination of surgery, radiation, and/or systemic therapy, namely chemotherapy or targeted agents. The expression of the epidermal growth factor receptor (EGFR) has been detected in more than 90% of all cases of SCCHN and has been correlated with decreased survival rates, resistance to radiotherapy, loco-regional treatment failure, and increased rates of distant metastases. This paper discusses several strategies aimed at targeting EGFR in combination with radiation. Until now, cetuximab, an anti-EGFR monoclonal antibody, is the only targeted agent that has been shown to improve overall survival in combination with radiation therapy. However, considering that there are multiple mechanisms of primary and acquired resistance to EGFR inhibitors, we focused on dissecting molecular pathways of EGFR inhibition to find alternative or complementary strategies for increasing tumour responsiveness. We suggest that the combination of treatments targeting the EGFR pathway and drugs aimed at increasing immune responses represent a promising approach that deserves to be further explored.

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Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: A phase II, randomized, double-blind, placebo-controlled study

Cited by 48 publications

References 31 publications

Contrasted Outcomes to Gefitinib on Tumoral IGF1R Expression in Head and Neck Cancer Patients Receiving Postoperative Chemoradiation (GORTEC Trial 2004-02)

Contrasted Outcomes to Gefitinib on Tumoral IGF1R Expression in Head and Neck Cancer Patients Receiving Postoperative Chemoradiation (GORTEC Trial 2004-02)

Place in Concomitant Use with Anti-EGFR Radiotherapy in Locally Advanced Head and Neck Cancer Treatment

Radiotherapy plus EGFR inhibitors: synergistic modalities

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