Evidence map›Paper›PMID 27289242›Full record

ArticleInvestigational new drugs2016

Phase I trial of dacomitinib, a pan-human epidermal growth factor receptor (HER) inhibitor, with concurrent radiotherapy and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (XDC-001).

Amy Prawira, Irene Brana-Garcia, Anna Spreafico, Andrew Hope, John Waldron, Albiruni R Abdul Razak, Eric X Chen, Raymond Jang, Brian O'Sullivan, Meredith Giuliani and 7 more

Abstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Amy PrawiraDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Irene Brana-GarciaDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Anna SpreaficoDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Andrew HopeDepartment of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
John WaldronDepartment of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Albiruni R Abdul RazakDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Eric X ChenDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Raymond JangDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Brian O'SullivanDepartment of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Meredith GiulianiDepartment of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Andrew BayleyDepartment of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
John ChoDepartment of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Lisa WangDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Bayardo Perez-OrdonezDepartment of Pathology, University Health Network, Toronto, ON, Canada.
Ilan WeinrebDepartment of Pathology, University Health Network, Toronto, ON, Canada.
Lillian L SiuDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Aaron R HansenDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. aaron.hansen@uhn.ca.
University of Toronto · CAPrincess Margaret Cancer Centre · CAUniversity Health Network · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background Curative-intent, non-surgical treatment options for locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) include radiotherapy with/without chemotherapy or radiotherapy with cetuximab. This single institution phase I dose escalation trial tested the pan-human epidermal growth factor receptor (HER) oral tyrosine kinase inhibitor, dacomitinib, in combination with standard cisplatin-based chemoradiotherapy. Methods Patients received oral dacomitinib once daily at 3 protocol-defined dose levels (15 mg, 30 mg, and 45 mg). Cisplatin was given intravenously at 100 mg/m(2) every 3 weeks. Radiotherapy was delivered using intensity modulated radiation therapy (IMRT) to a dose of 70Gy in 35 daily fractions to the primary and nodal disease. Dose escalation was performed using a standard 3 + 3 design. Results Twelve patients with LA-SCCHN were enrolled between January 2013 and August 2014. No dose limiting toxicities (DLTs) were observed in the 15 mg and 30 mg dose levels. In the 45 mg dose level, one of four evaluable patients developed a DLT with intolerable grade 2 diarrhea requiring discontinuation of therapy. Adverse events (AEs) attributed to dacomitinib alone include diarrhea, hypertension, and acneiform and maculopapular rash. The most common non-hematological AEs include weight loss, diarrhea, dry mouth, mucositis, nausea, hypoalbuminemia, and hyponatremia. Frequency and severity of AEs did not increase with increasing dose levels of dacomitinib. All patients completed the full course of radiotherapy on schedule and the median dose of cisplatin was 200 mg/m(2), which is comparable to historical standards. Of the 10 patients evaluable for response, 1 patient relapsed with metastatic disease. Conclusions The triple combination has a tolerable side effect profile and dose levels 15 mg and 30 mg were cleared safely. The addition of dacomitinib did not preclude delivery of standard chemoradiotherapy. Studies testing the addition of other HER-targeted therapies to platinum-based concurrent chemo-radiotherapy in LA-SCCHN have failed to demonstrate improved patient outcomes and have reported trends towards excessive toxicities. These results generated uncertainty regarding the future of these agents in combination with chemo-radiation for the treatment of LA-SCCHN, which ultimately led to the early termination of this study.

Indexed as

ChemoradiotherapyAdultAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCisplatinErbB ReceptorsFemaleHead and Neck NeoplasmsHumansMaleMiddle AgedProtein Kinase InhibitorsQuinazolinonesSquamous Cell Carcinoma of Head and NeckAntineoplastic AgentsCisplatindacomitinibErbB ReceptorsProtein Kinase InhibitorsQuinazolinonesConcurrent cisplatin with radiotherapyDacomitinibSquamous cell carcinoma of the head and neck

Identifiers

PMID27289242
OpenAlexW2415636816

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.