Rate of Pathologic Complete Responses to Docetaxel, Cisplatin, and Fluorouracil Induction Chemotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck

Haddad, Robert I.; Tishler, Roy B.; Wirth, Lori J.; Norris, Charles M.; Goguen, Laura A.; Sullivan, Christopher A.; O’Donnell, L.; Li, Yang; Posner, Marshall R.

doi:10.1001/archotol.132.6.678

Cited by 25 publications

(13 citation statements)

References 23 publications

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“…Notably, response rates, though generally impressive appear lower than those seen with TPF chemotherapy, but significantly greater than those seen with single agent immunotherapy in the recurrent and metastatic setting [14]. Response rates have proven a poor marker of the efficacy of immunotherapy and the true measure of the success or failure of neoadjuvant immunotherapy must be in the hard end points of disease free survival (DFS) and OS.…”

Section: Discussionmentioning

confidence: 99%

“…Induction chemotherapy may still be considered in select clinical situations after multi-disciplinary discussion, but its routine use is not supported by the available data, except as a treatment option in larynx preservation [12]. When induction chemotherapy is administered, TPF is the preferred regimen [13,14]. The potential of increased toxicity interfering with receipt of chemoradiation remains a challenge [4,15].…”

Section: Induction Chemotherapy In Non-surgical Managementmentioning

confidence: 99%

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The neoadjuvant paradigm reinvigorated: a review of pre-surgical immunotherapy in HNSCC

Stafford

Kaczmar

2020

Cancers Head Neck

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Background: There remains up to a 50% recurrence rate in advanced p16-head and neck squamous cell carcinoma with current standard of care treatment. In an attempt to improve survival, multiple trials administering induction or neoadjuvant chemotherapy have been conducted but none demonstrated improved overall survival. The established efficacy of immune checkpoint inhibitors in the recurrent and metastatic setting has produced widespread interest in their neoadjuvant use. Purpose: To survey the landscape of active neoadjuvant immunotherapy trials in head and neck squamous cell carcinoma and summarize and synthesize currently available outcomes from these trials. Conclusions: Neoadjuvant immunotherapy has proven safe and well tolerated in head and neck squamous cell carcinoma with encouraging efficacy results, including relatively high rates of pathologic response. Ongoing studies offer an opportunity to study immune responses in vivo. PD-L1 positivity, high tumor mutational burden and infiltration of NK cells, CD8, CD26 and Tim3 positive lymphocytes at time of surgery have been correlated with pathologic responses. We await updated reports of disease free survival and overall survival data and results of ongoing phase III studies utilizing neoadjuvant immunotherapy to determine if this treatment paradigm will have a place in the standard of care treatment in head and neck squamous cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Induction Chemotherapy In Non-surgical Managementmentioning

confidence: 99%

The neoadjuvant paradigm reinvigorated: a review of pre-surgical immunotherapy in HNSCC

Stafford

Kaczmar

2020

Cancers Head Neck

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“…Although several chemotherapeutic drugs, including cisplatin, have proven effective in the treatment of head and neck cancer [49–51], the failure of OSCCs to respond to chemotherapeutic treatments due to acquired resistance limits the overall success of these types of therapeutic strategies and in-part contributes to ~40% of oral cancer-related patient deaths [5, 52]. Therefore, to assess whether the depletion of Dicer1e could contribute towards the chemosensitization of oral cancer cells, we transfected SCC-25 cells with either siNT or siDicer1e 24 hours prior to the addition of 1.8 μM (IC 25 ) of cisplatin for 48 hours.…”

Section: Resultsmentioning

confidence: 99%

Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral cancer cells

et al. 2014

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BackgroundThe human dicer1 gene has been predicted to produce several mRNA variants that encode truncated Dicer1 proteins of varying lengths. One of these Dicer1 variants, Dicer1e, was recently found to be differentially expressed in breast cancer cells. Because the expression and function of the Dicer1e protein variant has not been well characterized and the underlying molecular mechanisms for the development of oral squamous cell carcinomas (OSCCs) are poorly understood, the present study sought to characterize the biological role of Dicer1e and determine its relationship, if any, to OSCC pathogenesis.MethodsWestern blot analyses were used to examine Dicer1e expression levels in a panel of oral cancer cells/tissues and during epithelial-mesenchymal transition (EMT), followed by 5′/3′-RACE analyses to obtain the full-length Dicer1e transcript. Biochemical fractionation and indirect immunofluorescent studies were performed to determine the cellular localization of Dicer1e and the effects of Dicer1e silencing on cancer cell proliferation, clonogenicity, and drug sensitivity were also assessed.ResultsDicer1e protein levels were found to be overexpressed in OSCC cell lines of epithelial phenotype and in OSCC tissues with its levels downregulated during EMT. Moreover, the Dicer1e protein was observed to predominantly localize in the nucleus. 5′/3′-RACE analyses confirmed the presence of the Dicer1e transcript and silencing of Dicer1e impaired both cancer cell proliferation and clonogenicity by inducing either apoptosis and/or G2/M cell cycle arrest. Lastly, Dicer1e knockdown enhanced the chemosensitivity of oral cancer cells to cisplatin.ConclusionThe expression levels of Dicer1e influence the pathogenesis of oral cancer cells and alter their response to chemosensitivity, thus supporting the importance of Dicer1e as a therapeutic target for OSCCs.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-190) contains supplementary material, which is available to authorized users.

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Section: Perspectivementioning

confidence: 99%

“…Several groups aimed to investigate the clinical benefit, if any, of adding taxane therapy to the IC regimen. A series of phase I and phase II trials used a high-and intermediate-dose docetaxel, cisplatin, and 5-FU (TPF)-based IC regimen for patients with advanced SCCHN [21][22][23][24].Following phase II trials involving the addition of taxane therapy, three randomized phase III trials emerged to explore the benefit of induction TPF versus PF alone in terms of clinical outcomes (Table 2). In the European TAX-323 study, 358 patients with stage III or stage IV unresectable disease and no evidence of distant metastasis (80% of patients included had T3 or T4 lesions and 71% had N2 or N3 nodal disease) were randomized to TPF (docetaxel, 75 mg/m 2 on day 1; cisplatin, 75 mg/m 2 on day 1; 5-FU, 750 mg/m 2 by continuous infusion for 5 days) or PF therapy (cisplatin, 100 mg/m 2 ; 5-FU, 1,000 mg/m 2 by continuous infusion on days 1-5) for up to four cycles followed by RT in both treatment arms [4].…”

mentioning

confidence: 99%

Induction Chemotherapy for Locoregionally Advanced Head and Neck Cancer: Past, Present, Future?

2013

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The treatment of patients with locoregionally advanced squamous cell cancer of the head and neck is still evolving. Induction chemotherapy (IC) is widely used in this patient population and it is unclear how to best incorporate IC into multimodality treatment. Recently, the results of two randomized clinical trials were presented (the PARADIGM and Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer trials), which showed no demonstrable benefit of IC followed by concurrent chemoradiation over concurrent chemoradiotherapy alone. However, a lower rate of distant metastatic disease was noted, suggesting that patients who are at high risk for metastatic disease may benefit from IC. This review summarizes how IC has evolved over the years, provides an update of recent developments, and discusses how IC may develop in the future. The Oncologist 2013;18:288 -293 Implications for Practice: Chemotherapy remains an integral part of management of the patient with locoregionally advanced squamous cell cancer of the head and neck. Data from recent trials do not show a survival advantage from induction chemotherapy (IC) over concurrent chemoradiation, but there are significant limitations to these studies as detailed in this review. IC remains an option for treating locoregionally advanced disease and could be considered for patients who are at high risk for distant failure. PERSPECTIVEMalignancies of the head and neck account for an estimated 52,160 newly diagnosed cancers in the U.S. each year, and nearly 12,000 deaths [1]. Squamous cell carcinoma of the head and neck (SCCHN) accounts for 90% of such malignancies. Despite treatment advances and early multimodality therapy, 5-year survival rates have remained dismal for patients with locoregionally advanced disease [2][3][4].Treatment strategies for patients with locoregionally advanced SCCHN have moved away from poorly effective singlemodality therapy and now encompass a multimodality approach (surgery, chemotherapy, radiation [RT], and targeted molecular therapeutics). In 2009, a large meta-analysis of the use of chemotherapy in head and neck cancer was updated, incorporating data from 87 trials and 17,346 patients, confirming the benefit of chemotherapy (given as concurrent chemoradiotherapy [CRT], induction chemotherapy [IC], or adjuvant treatment) in patients with locoregionally advanced SCCHN at all tumor sites (Table 1) [5,6]. The observed benefit of chemotherapy was an absolute 4.5% higher 5-year survival rate. Subgroup analysis revealed that there was a 2.4% overall survival (OS) benefit in favor of IC (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.90 -1.02; p ϭ .18) compared with locoregional treatment with concomitant CRT, with 26 of the 31 induction trials combining 5-fluorouracil (5-FU) and platinum therapy. Although the risk for death was lower in patients who were treated with concomitant CRT (HR, 0.81; 95% CI, 0.78 -0.86) in the indirect comparison, there was a more pronounced effec...

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Rate of Pathologic Complete Responses to Docetaxel, Cisplatin, and Fluorouracil Induction Chemotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck

Abstract: Objective: To report the rate of pathological complete response after induction chemotherapy with the docetaxel, cisplatin, and fluorouracil (TPF) combination.

Cited by 25 publications

References 23 publications

The neoadjuvant paradigm reinvigorated: a review of pre-surgical immunotherapy in HNSCC

The neoadjuvant paradigm reinvigorated: a review of pre-surgical immunotherapy in HNSCC

Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral cancer cells

Induction Chemotherapy for Locoregionally Advanced Head and Neck Cancer: Past, Present, Future?

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