scholarly journals Genetic Variants as Predictive Markers for Ototoxicity and Nephrotoxicity in Patients with Locally Advanced Head and Neck Cancer Treated with Cisplatin-Containing Chemoradiotherapy (The PRONE Study)

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 551 ◽  
Author(s):  
Chantal M. Driessen ◽  
Janneke C. Ham ◽  
Maroeska te Loo ◽  
Esther van Meerten ◽  
Maurits van Lamoen ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Side Effects ◽  
Creatinine Clearance ◽  
Head And Neck ◽  
Neck Cancer ◽  
Genetic Variants ◽  
Locally Advanced ◽  
Added Value ◽  
Advanced Head ◽  
Patient Reported

Ototoxicity and nephrotoxicity are potentially irreversible side effects of chemoradiotherapy with cisplatin in locally advanced head and neck cancer (LAHNC) patients. Several predictive genetic variants have been described, but as yet none in LAHNC patients. The aim of this study is to investigate genetic variants as predictors for ototoxicity and nephrotoxicity in LAHNC patients treated with cisplatin-containing chemoradiotherapy. Our prospective cohort of 92 patients was genotyped for 10 genetic variants and evaluated for their association with cisplatin-induced ototoxicity (ACYP2, COMT, TPMT and WFS1) and nephrotoxicity (OCT2, MATE and XPD). Ototoxicity was determined by patient-reported complaints as well as tone audiometrical assessments. Nephrotoxicity was defined as a decrease of ≥25% in creatinine clearance during treatment compared to baseline. A significant association was observed between carriership of the A allele for rs1872328 in the ACYP2 gene and cisplatin-induced clinically determined ototoxicity (p = 0.019), and not for ototoxicity measured by tone audiometrical assessments (p = 0.449). Carriership of a T allele for rs316019 in the OCT2 gene was significantly associated with nephrotoxicity at any time during chemoradiotherapy (p = 0.022), but not with nephrotoxicity at the end of the chemoradiotherapy. In conclusion, we showed prospectively that in LAHNC patients genetic variants in ACYP2 are significantly associated with clinically determined ototoxicity. Validation studies are necessary to prove the added value for individualized treatments plans in these patients.

A phase I/II trial of induction chemotherapy followed by concomitant docetaxel with concomitant boost radiotherapy (CBR) and amifostine for advanced head and neck cancer (HNC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15525-15525 ◽  
Author(s):  
C. Saurel ◽  
R. Meredith ◽  
J. A. Bonner ◽  
G. Peters ◽  
W. Carroll ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Side Effects ◽  
Phase I ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Neck Cancer ◽  
Distant Metastasis ◽  
Locally Advanced ◽  
Primary Chemotherapy ◽  
Advanced Head

15525 Background: Concomitant chemo-radiation for head and neck cancer has emerged as the optimal method of treating advanced head and neck cancers, although the acute and late toxicities can be formidable. The addition of induction chemotherapy to concomitant chemo-radiation for head and neck cancer is designed to impact the incidence of distant metastasis while delivering aggressive local treatment. This trial evaluates the tolerability and effectiveness of induction chemotherapy followed by CBR with concurrent docetaxel and subcutaneous (SC) amifostine in locally advanced squamous cell carcinoma of the head and neck (SCCHN). Methods: Patients with stage III/IV nonmetastatic SCCHN received 3 cycles of primary chemotherapy with docetaxel and cisplatin, each at 75 mg/m2. Patients then received 4 weekly doses of docetaxel at 20 mg/m2 with concurrent CBR. SC amifostine was given at a dose of 500 mg in divided doses during each day of XRT. Results: The phase I component defined the MTD of concurrent docetaxel as 20 mg/m2 for 4 cycles during CBR. 18 patients are evaluated for response. No patient developed progressive disease during primary chemotherapy. Grade 3–4 mucositis was common, but all patients completed the planned concomitant docetaxel. At 6 months after treatment, 7/18 patients still used a feeding tube, though most have had them subsequently removed. Amifostine given by SC was well tolerated; 7 patients developed transient hypotension not requiring any intervention, with grade1 dermatitis and nausea reported. 2 patients discontinued amifostine due to rash or persistent hypotension. Conclusions: Response to induction chemotherapy was greater then 75% by radiological assessment, with no patient developing distant metastasis thus far. Local control has been excellent but side effects from docetaxel and CBR have necessitated prolonged use of feeding tubes for up to 6 months. SC amifostine has been well tolerated without significant side effects. This aggressive therapy is effective treatment for locally advanced SCCHN. No significant financial relationships to disclose.

Long-Term Outcomes after Double Free Flap Reconstruction for Locally Advanced Head and Neck Cancer

2018 ◽  
Vol 35 (01) ◽  
pp. 066-073 ◽  
Author(s):  
J. Brinkman ◽  
Shoista Kambiz ◽  
Tim de Jong ◽  
Marc Mureau
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Free Flap ◽  
Patient Survival ◽  
Locally Advanced ◽  
Free Flaps ◽  
Advanced Head ◽  
Patient Reported

Background The use of simultaneous, multiple free flaps has become a reliable reconstructive option in patients with extensive composite defects after resection of locally advanced head and neck cancer. However, some reluctance remains among reconstructive surgeons with concerns regarding flap outcomes and limited patient survival. Therefore, we evaluated complications, long-term patient survival, and patient-reported outcomes following these extensive head and neck reconstructions. Methods All consecutive patients treated with multiple free flaps for reconstruction of extensive composite defects after resection of locally advanced head and neck cancer between 1999 and 2014 were retrospectively reviewed. Patient charts were evaluated for demographics, treatment details, complications, and patient survival. In addition, all patients alive at the start of the study were asked to complete the 10-item Eat Assessment Tool (EAT-10) and the Intelligibility Rating Scale (IRS). Results Eighty-four simultaneous, multiple free flaps were performed in 42 patients. The predominant free flap combination consisted of a fibula with either an anterolateral thigh (n = 22) or a radial forearm flap (n = 14). Complete flap survival was 95%. Nineteen patients were still alive with a mean follow-up of 55 months. Five-year patient survival was 46.3%. Mean EAT-10 score was 8.4 (range: 0–29), with only one patient reporting problematic swallowing. Ninety percent of the patients had moderate to good speech intelligibility with the IRS. Conclusion Multiple, simultaneous free flaps can be performed safely, leading to acceptable long-term patient survival and patient-reported functional outcomes. Our study demonstrates that it is worthwhile to perform these challenging microvascular reconstructions in patients with locally advanced head and neck cancer.

Toxicity induced by radiochemotherapy with weekly paclitaxel versus weekly cisplatin in patients with advanced head and neck cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16534-16534
Author(s):  
D. L. Stanculeanu ◽  
A. Tache ◽  
A. Cringeanu ◽  
D. Mitulescu ◽  
R. Scheusan ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Side Effects ◽  
Head And Neck ◽  
Neck Cancer ◽  
Locally Advanced ◽  
External Beam Radiation ◽  
Weekly Paclitaxel ◽  
Severe Side Effect ◽  
Advanced Head ◽  
Grade 3

16534 Background: Head and neck cancers represent about 8 % of the total solid cancer cases. For advanced head and neck cancer (HNC) patients, the effects of disease and the side effects of aggressive treatments have the potential to severely affect quality of life. Combined chemoradiotherapy increase rates of locoregional control, but it may cause severe side effects, mainly painful mucositis. In our study we evaluated the chemoradiotherapy induced toxicities in patients treated with concomitant radiochemotherapy using weekly paclitaxel or cisplatin for advanced head and neck cancer. Methods: From April 2003 to December 2005 46 patients with locally advanced head and neck cancer were enrolled onto this study. Patients characteristics: 35 male and 11 female; mean age 62,5; performance status ECOG 0–1, carcinoma histological confirmed. All patients received external beam radiation using DT= 45 Gy, 1,8 Gy/fr, 5 fr/week in combination with chemotherapy: arm A (20 pts) - Paclitaxel 35 mg/mp days 1,8,15,22,29; arm B (26 pts)- Cisplatin 20 mg/mp days 1,8,15,22,29. Results: 40 patients have completed the planed treatment; 4 patients have interrupted treatment because of toxicity; there were 2 toxic death due to neutropenic sepsis and metabolic disorders in arm A. Toxicity grade 3–4 was hematological - neutropenia - 14, 6 % pts in arm A vs. 7, 8 % pts in arm B; gastrointestinal - nausea 6,7 % pts in arm A vs. 5,6% pts in arm B; neurological - neuropathy 5,4 % pts in arm A vs. 0 pts in arm B; dermatological - radic dermitis 4,3% in arm A vs. 4,1% in arm B; oral mucositis 33,6% in arm A vs 27,8% in arm B. All this patients received analgesics and anti-inflammatory drugs, systemic and/or topical. Other toxicities were not significantly related. Conclusions: This study confirmed that radiochemotherapy has shown to provide clinical benefit response and disease stabilization in patients with locally advanced head and neck cancer. Unfortunately, this concomitant therapy was significantly associated with hematological toxicities and oral mycosis. The most severe side effect was oral mycositis grade 3–4, especially in the paclitaxel arm. No significant financial relationships to disclose.

Phase II trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and intensity moduled radiation therapy (IMRT) for locally advanced head and neck cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6014-6014
Author(s):  
J. Kao ◽  
L. Policarpio ◽  
M. Teng ◽  
R. Burri ◽  
E. Genden ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Phase Ii ◽  
Neck Cancer ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Locally Advanced ◽  
Radiation Dermatitis ◽  
Advanced Head ◽  
Patient Reported

6014 Background: This phase II study was conducted to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated boost intensity modulated radiation (SIB-IMRT) into a well-described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Endpoints included overall survival (OS), locoregional (LRC) and (DC), quality of life and toxicity. Methods: Patients with stage IVa-IVb or high-risk stage III squamous cell carcinomas were enrolled on a phase II trial. Prior organ-conserving surgical therapy or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low (43.2 to 48 Gy) and intermediate (54 to 63 Gy) risk volumes. A separate IMRT conedown plan was targeted to gross disease (72 Gy). The median radiation dose was 72 Gy (range 60 to 72 Gy) administered in 1.5 Gy fractions BID on weeks 1, 3, 5, 7 ± 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg BID) and cetuximab (250 mg/m2). Results: From January 2007 to April 2008, 33 subjects enrolled. Characteristics included 24 males; median age 59; ECOG performance status was 0 in 12. Disease was stage IVa-b disease in 31 (94%), T3–4 in 16 (48%), N2–3 in 23 (70%), and oropharynx primary in 15 (45%). Median follow-up in surviving patients is 15 months (range 6 to 22 months). The 1 year LRC, DC and OS is 91%, 82%, and 92%, respectively. Grade 3 toxicity consisted of mucositis (33%), radiation dermatitis (15%), anemia (15%), and leukopenia (15%), and neutropenia (9%). There were no grade 4–5 events. The majority of patients (64%) were able to tolerate treatment without a feeding tube. Median patient reported University of Washington QOL-R scores before, immediately after, 3 months and 8 months after chemoradiation were 85.5 (±14), 65 (±13), 76.5 (±15), and 84.5 (±9), respectively. Conclusions: Concurrent 5-FU, HU, cetuximab, and SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy in the curative therapy of locally advanced head and neck cancer. [Table: see text]

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