Glutathione-S-transferase genes polymorphisms predict response and progression free survival in head and neck cancer patients treated with cisplatin based chemoradiotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21127-21127
Author(s):  
M. H. Federico ◽  
K. C. Brunialti ◽  
G. Castro ◽  
F. S. Pasini ◽  
S. Maistro ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Progression Free Survival ◽  
Polymorphic Variant ◽  
Wild Type ◽  
Glutathione S Transferase ◽  
Free Survival ◽  
Gstp1 Ile105val

21127 Background: Alterations in the function of DNA repair genes and detoxification genes may influence response to cisplatin based chemoradiotherapy in patients (pts) with head and neck cancer. Our purpose was to evaluate the prognostic ability of polymorphisms of three genes glutathione S-transferase (GST), ERCC1 and XPD in patients with head and neck squamous cell carcinoma (HNSCC). Methods: A polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) or multiplex PCR approach was used to determine the frequency of the XPD Lys751Gln (n=29), ERCC1 Asn118 (n=50), GSTP1 Ile105Val (n=22) and GSTT1/GSTM1 (n=66), in DNA of peripheral lymphocytes. A total of 50 pts were treated with platinum based chemoradiotherapy exclusively and 16 pts received the same regimen in the adjuvant setting. Median follow-up was 6.4 months and 17 pts had tumor progression and 2 died, with a progression free survival (PFS) of 18 months. Results: The frequencies (%) of the distinct genotypes were, respectively, for the homozygous common allele and heterozygous plus homozygous polymorphic variant: 40 and 60 for ERCC1; 48 and 52 for XPD; 36 and 64 for GSTT/GSTM1, 41 and 59 for GSTP1. We did not observe any association between ERCC1, XPD, GSTM1/GSTT1 polymorphisms and response, but for GSTP1, the polymorphic variant was associated with tumor response, as compared to wild type (p=0.069 χ2 test). In relation to PFS, no associations were found between XPD, ERCC1 and GSTP1, however, for GSTM1/GSTT1, the null or heterozygous genotype (median survival: not reached, n=43) was associated with a better PFS, as compared to the wild type (18 months, n=23; p=0.087, Log-rank). Conclusions: Among the polymorphic variants studied here, our impression is that GST is the most powerful prognostic factor of favorable response and PFS to cisplatin based chemoradiotherapy in HNSCC. Supported by CAPES. No significant financial relationships to disclose.

scholarly journals Effectiveness of nivolumab affected by prior cetuximab use and neck dissection in Japanese patients with recurrent or metastatic head and neck cancer: results from a retrospective observational study in a real-world setting

2021 ◽  
Author(s):  
Shin Kariya ◽  
Yasushi Shimizu ◽  
Nobuhiro Hanai ◽  
Ryuji Yasumatsu ◽  
Tomoya Yokota ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Dissection ◽  
Neck Cancer ◽  
Median Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Free Survival

Abstract Background To examine the effect of prior use of cetuximab and neck dissection on the effectiveness of nivolumab, we conducted a large-scale subgroup analysis in Japanese patients with recurrent/metastatic head and neck cancer. Methods Data on the effectiveness of nivolumab were extracted from patient medical records. All patients were analyzed for effectiveness by prior cetuximab use. In the analyses for prior neck dissection, only patients with locally advanced disease were included. Results Of 256 patients analyzed, 155 had received prior cetuximab. Nineteen of 50 patients with local recurrence underwent neck dissection. The objective response rate was 14.7 vs 17.2% (p = 0.6116), median progression-free survival was 2.0 vs 3.1 months (p = 0.0261), and median overall survival was 8.4 vs 12 months (p = 0.0548) with vs without prior cetuximab use, respectively. The objective response rate was 23.1 vs 25.9% (p = 0.8455), median progression-free survival was 1.8 vs 3.0 months (p = 0.6650), and median overall survival was 9.1 vs 9.9 months (p = 0.5289) with vs without neck dissection, respectively. Conclusions These findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck dissection history. Trial registration number UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

scholarly journals Cisplatin, Docetaxel and Cetuximab (TPEx) as First-line Treatment for Patients With Recurrent or Metastatic Head and Neck Cancer: A Multicenter Real-World Study

2020 ◽  
Author(s):  
Agustín Falco ◽  
Mariano Leiva ◽  
Albano Blanco ◽  
Guido Cefarelli ◽  
Andrés Rodriguez ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Real World ◽  
Progression Free Survival ◽  
First Line ◽  
Multicenter Cohort Study ◽  
Free Survival ◽  
Overall Response ◽  
Median Progression Free Survival

Abstract BACKGROUNDThe association of platinum, taxanes, and cetuximab has proven to be an effective and safe strategy for head and neck cancer treatment. Here we present a multi-institutional real-world experience of the TPEx schema as first-line therapy in advanced squamous cell carcinoma of the head and neck (SCCHN).METHODS This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx regimen at five medical centers in Argentina between January 1, 2017, and April 31, 2020. Chemotherapy consisted of four cycles of docetaxel, cisplatin, and cetuximab, followed by cetuximab maintenance. Clinical outcomes and toxicity profiles were evaluated. RESULTSTwenty-four patients were included. Median age at diagnosis was 58 years (range 36-77). The majority of patients (83.3%) received at least four chemotherapy cycles in the initial part. In the included group, overall response rate was 62.5%, and three patients achieved a complete response (12.5%). The median time to response was 2.4 months (95% CI 1.3-3.5). With a median follow-up of 12.7 months (95% CI 8.8-16.6), the median progression-free survival was 6.9 months (95% CI: 6.5-7.3), and the overall survival rate at 12 months was 82.4%. Two-thirds of patients reported at least one treatment-related adverse event, and 25% presented grade 3-4 toxicities.CONCLUSIONSTPEx was an adequately tolerated regimen in our population. Median progression-free survival and overall response rates were consistent with recent reports in clinical trials evaluating this treatment combination.

scholarly journals Association between severe treatment-related lymphopenia and progression-free survival in patients with newly diagnosed squamous cell head and neck cancer

Head & Neck ◽  
2014 ◽  
Vol 36 (12) ◽  
pp. 1747-1753 ◽  
Author(s):  
Jian L. Campian ◽  
Guneet Sarai ◽  
Xiaobu Ye ◽  
Shanthi Marur ◽  
Stuart A. Grossman
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival

Recombinant adenoviral human p53 gene combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16011-e16011 ◽  
Author(s):  
Jihong Shu
Keyword(s):  
Overall Survival ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Progression Free Survival ◽  
P53 Gene ◽  
Intratumoral Injection ◽  
Comprehensive Treatment ◽  
Local Progression

e16011 Background: In head and neck cancer, p53 mutations are present in up 60% of head and neck cancers. Studies indicated p53 gene could increase both radio- and chemo-sensitivities. In this study, we investigate the effectiveness of recombinant adenoviral human p53 gene (rAd-p53) combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer. Methods: From May 2008 to Dec. 2011, 48 patients with an advanced unresectable head and neck cancer, 29 males and 18 females with an average of 61.3 years old, were included this study. Those patients were treated with intratumoral injection of rAd-p53 at a dose 1-3 ×1012 viral particles (VP) , once every 3 days for 6 times. Chemotherapy regimen consisted of cisplatin 60 mg/m2 on d1 and 5-Fu 600 mg/m2 on d1-5, given intravenously every 3 weeks for 3 cycles. Radiation were given at a dose of 2Gy/f, five fractions a week for a total dose 50~70Gy. Patients were monitored for response, long-term efficacy and adverse events. Results: The median follow-up time was 21.2 months (6~39 months). Overall response rate was 91.7% (44/48), 47.9% (23/48) of complete responses and 43.8% (23/48) of partial responses. One-year overall survival was 79.2% and local progression-free survival was 70.8%. At the last follow-up, the overall survival was 72.9%. Forty-six patients experienced self-limited fever after administration of p53. Conclusions: rAd-p53 gene therapy as a component of comprehensive treatment for advanced unresectable head and neck cancer showed significant beneficial effects.

Intensity-modulated radiation therapy for head and neck cancer of unknown primary

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5565-5565 ◽  
Author(s):  
M. L. Klem ◽  
S. L. Wolden ◽  
M. J. Zelefsky ◽  
Y. B. Su ◽  
B. Singh ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Intensity Modulated Radiation Therapy ◽  
Distant Metastases ◽  
Unknown Primary ◽  
Free Survival ◽  
Esophageal Strictures ◽  
Peg Tube

5565 Background: Unknown primary head and neck cancers often require comprehensive mucosal and bilateral neck irradiation. With conventional techniques, significant toxicity can develop. Intensity modulated radiation therapy (IMRT) has the potential to minimize toxicity. Methods: From 2000–2005, 21 patients received IMRT for unknown primary head and neck cancer at our center. Median age was 57. Clinical stages were: TxN1: 43%; TxN2b:38%; TxN2c:5%; TxN3:14%. Five patients received IMRT with primary intent and 16 as postoperative therapy. Fourteen received concurrent chemotherapy, most with cisplatin (100mg/m2/cycle) or carboplatin (70mg/m2)/ 5FU (600mg/m2) every 3 weeks for 2–3 cycles. Seven received IMRT alone. Median dose was 66 Gy. PEG tube was placed in 13 patients. Toxicities were evaluated. Regional progression free survival (RPFS), distant metastases free survival (DMFS) and overall survival (OS) were calculated with Kaplan Meier curves. Results: Grade 1 and 2 xerostomia was seen in 57% and 43%. Salivary function improved with time. By 6 months, no patient had greater than grade 1 xerostomia. Grade 1, 2, and 3 acute skin toxicity and mucositis were seen in 67%, 29%, 5% and in 33%, 52%, 14%, respectively. PEG tube was required in 72% who had combined modality and 43% with IMRT alone. Of the 13 with PEG tubes, only 3 required PEG support at the time of last follow up. For those who had PEG removed, median time with PEG was 3.8 months from the end of RT. Two patients treated with combined modality and 1 treated with IMRT alone developed esophageal strictures, but all had improvement or resolution with dilation. Two patients had persistent disease after RT and 1 had late regional failure at 39 months. Two patients developed distant metastases and died. With a median follow up of 14.3 months (5.4–73.4), 2 year RPFS, DMFS, and OS were 88.9%, 89.4%, and 84.0%. Conclusions: Preliminary analysis of IMRT for unknown primary head and neck cancer shows acceptable toxicity and encouraging efficacy. Xerostomia was a common acute complication but patients had marked improvement by 6 months. Esophageal strictures were seen but effectively treated with dilation. Techniques to limit esophageal dose may help further minimize this complication. No significant financial relationships to disclose.

Optimal cumulative cisplatin dose for radio-sensitization in locally advanced head and neck cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18553-e18553
Author(s):  
Atanu Bhattacharjee ◽  
Vanita Noronha ◽  
Vijay Maruti Patil ◽  
Anuja Abhayankar ◽  
Amit Joshi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Cumulative Dose ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival

e18553 Background: Evidence to choose the optimum chemotherapy between weekly and 3 weekly cisplatin for prolonging the duration of progression free survival in head and neck squamous cell carcinoma (HNSCC) is equivocal. This urged us to look into the cumulative dose of chemotherapy rather than the frequency of administration i.e. weekly or 3 weekly. The aim of this study was to determine the optimal cumulative dose of cisplatin to improve the progression-free survival (PFS). Methods: Between January 2011 and January 2018, a total of 836 consecutive patients with histologically proven primary squamous cell carcinoma of the oral cavity, larynx, hypopharynx, and oropharynx were included. The effect of the cumulative dose on progression-free survival was studied to obtain the optimal cumulative dose of cisplatin. Results: A total of 11 cohorts were generated to represent the cumulative doses. The cumulative doses were measured at 30, 60, 90,120,150,180,200,210,240 and 300 mg/m2 respectively. The maximum duration of progression-free survival (PFS) was considered to define the best effective cumulative dose. Conclusions: This study confirms that a cumulative cisplatin dose of ~ 210 mg/m2 is optimum for increasing PFS in patients with head and neck cancer. Therefore, doses with weekly 30 mg/m2 for seven cycles or 3-weekly 70 mg/m2 for 3 cycles could be equally effective to prolong the PFS. Clinical trial information: CTRI/2012/10/003062, CTRI/2014/09/004980.

Comparison of triweekly cisplatin regimens in definitive chemoradiotherapy for locally advanced head and neck cancer: A propensity score matching analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18007-e18007
Author(s):  
Yu Fujiwara ◽  
Yasuyoshi Sato ◽  
Naoki Fukuda ◽  
Naomi Hayashi ◽  
Xiaofei Wang ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Propensity Score ◽  
Head And Neck ◽  
Propensity Score Matching ◽  
Neck Cancer ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Group A ◽  
Group B

e18007 Background: Concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. Three cycles of 100 mg/m2 CDDP for every three weeks (Q3W) are now recommended but compliance with CCRT is relatively low due to its severe toxicity. Therefore, the potential de-escalation strategies for LAHNC have been discussed to decrease the therapeutic toxicity. Methods: Patients with LAHNC who underwent definitive CCRT with CDDP between 2012 and 2018 at The Cancer Institute Hospital of Japanese Foundation for Cancer Research were analyzed. Patients were classified into two groups based on the planned CDDP dose: (A) 100 mg/m2 and (B) 80 mg/m2 Q3W for three times. One-to-one propensity score matching was performed to minimize bias between two groups. After patients in two groups were matched by using propensity score, the overall survival (OS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), and metastatic recurrence-free survival (MRFS) were analyzed by the Kaplan-Meier method with the Cox proportional hazards model. The follow-up term was set as two years to evaluate the early survival benefit. The dose and density of CDDP and the objective adverse events were also assessed. Results: A total of 304 patients were included with the median age of 62 (Interquartile range [IQR]: 54-67) years. Among them, 249 patients (82%) were male. Patients were treated with 100 mg/m2 CDDP (n = 145) and 80 mg/m2 CDDP (n = 159) regimens. After the propensity score matching, 119 patients were included in each group, respectively. There were no significant differences in baseline characteristics between two propensity-matched cohorts. The median follow-up time was 24 months in each group. Two-year OS was 93.0% (95% confidence interval [CI]: 88.4-97.8) in group A and 94.9% (91.0-99.0) in group B. Two-year RFS was 86.5% (80.6-92.9) in group A and 83.1% (76.6-90.1) in group B, respectively. No significant difference was observed in OS (Hazard ratio [HR] = 1.42, 95% CI: 0.49-4.08, p = 0.52), RFS (HR = 0.81, 95% CI: 0.42-1.57, p = 0.54), LRFS (HR = 0.57, 95% CI: 0.24-1.36, p = 0.20), and MFS (HR = 1.32, 95% CI: 0.52-3.35, p = 0.56). The median cumulative dose of CDDP was significantly higher in group A (300 mg, interquartile range [IQR]: 240-300) than in group B (240 mg, IQR:160-240) but the frequency of hematological, hepatic, renal, electrolytic, and grade 3-5 any adverse events was not significantly different between two groups. Conclusions: Our study showed no survival difference at 2-year follow-up between 100 mg/m2 and 80 mg/m2 CDDP regimens of definitive CCRT for LAHNC. This result could support the tide of the de-escalation strategy in head and neck cancer treatment. Longer follow-up is necessary and further prospective trials comparing CDDP dosage are warranted.

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