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BMC Cancer. 2015 Oct 16;15:725. doi: 10.1186/s12885-015-1776-x.

CYP39A1 polymorphism is associated with toxicity during intensive induction chemotherapy in patients with advanced head and neck cancer.

Melchardt T1,2,3, Hufnagl C4,5,6, Magnes T7,8,9, Weiss L10,11,12, Hutarew G13, Neureiter D14, Schlattau A15, Moser G16, Gaggl A17, Tränkenschuh W18, Greil R19,20,21, Egle A22,23,24.

Author information

1
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.melchardt@salk.at.
2
Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.melchardt@salk.at.
3
Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.melchardt@salk.at.
4
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. cl.hufnagl@salk.at.
5
Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. cl.hufnagl@salk.at.
6
Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. cl.hufnagl@salk.at.
7
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.magnes@salk.at.
8
Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.magnes@salk.at.
9
Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. t.magnes@salk.at.
10
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. lu.weiss@salk.at.
11
Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. lu.weiss@salk.at.
12
Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. lu.weiss@salk.at.
13
Institute of Pathology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. g.hutarew@salk.at.
14
Institute of Pathology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. d.neureiter@salk.at.
15
Institute of Radiology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.schlattau@salk.at.
16
Department of Otorhinolaryngology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. g.moser@salk.at.
17
Department of Oral and Maxillofacial Surgery, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.gaggl@salk.at.
18
Institute of Pathology, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. w.traenkenschuh@salk.at.
19
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. r.greil@salk.at.
20
Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. r.greil@salk.at.
21
Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. r.greil@salk.at.
22
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.egle@salk.at.
23
Salzburg Cancer Research Institute (SCRI), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.egle@salk.at.
24
Cancer Cluster Salzburg (CCS), Müllner-Hauptstrasse 48-5020, Salzburg, Austria. a.egle@salk.at.

Abstract

BACKGROUND:

Induction chemotherapy incorporating docetaxel, cisplatin and 5- fluorouracil before radiotherapy may improve the outcome of patients with advanced head and neck cancer. Nevertheless, the addition of docetaxel increases hematological toxicity and infectious complications. Therefore, genetic markers predicting toxicity and efficacy of this treatment regimen may help to identify patients, who would have the most benefit from this intensive treatment.

METHODS:

A cohort of 78 patients with advanced head and neck cancer treated with induction chemotherapy was assessed for clinical outcome and toxicity during treatment with curative intention. Genetic polymorphisms primary associated with treatment efficacy (ERCC2-rs13181, rs1799793, ERCC1-rs3212986, rs11615, XRCC1-rs25487) or with docetaxel caused toxicity (CYP39A1-rs7761731, SLCO1B3-rs11045585) were evaluated in all patients. The results of these analyses were correlated with the clinical outcome of the patients (loco regional control, progression free survival, overall survival) and treatment related toxicity during induction chemotherapy.

RESULTS:

Median progression free survival and overall survival was 20 and 31 months in an intention to treat analysis, respectively. Overall response rate to induction chemotherapy was high with 78.1 % of all patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. Genotype A of the CYP39A1 rs7761731 polymorphism was associated with a higher incidence of leucopenia and infections or death during induction chemotherapy.

CONCLUSIONS:

Intensive induction chemotherapy results in a high response rate in the majority of patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. The CYP39A1 polymorphism rs7761731 may help to identify patients at high risk for treatment related toxicity.

PMID:
26475344
PMCID:
PMC4609094
DOI:
10.1186/s12885-015-1776-x
[Indexed for MEDLINE]
Free PMC Article

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