Intensive concomitant chemoradiotherapy in locally advanced unresectable squamous cell carcinoma of the head and neck: a phase II study of radiotherapy with cisplatin and 7-week continuous infusional fluorouracil.

1996 ◽  
Vol 14 (4) ◽  
pp. 1192-1200 ◽  
Author(s):  
P Wibault ◽  
M A Bensmaine ◽  
M de Forni ◽  
J P Armand ◽  
E Tellez Bernal ◽  
...  

PURPOSE To evaluate an intensive concomitant chemoradiotherapy protocol of conventional radiotherapy with intermittent cisplatin (CDDP) and continuous-infusion fluorouracil (5-FU) in unresectable, locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Fifty-seven patients with unresectable stage IV MO disease (International Union Against Cancer [UICC]/American Joint Committee on Cancer [AJCC], 1987) received radiotherapy 70 Gy followed by CDDP 80 mg/m2 and 5-FU 300 mg/m2/d. Response was assessed 2 months after treatment completion. RESULTS Thirty patients (52%) received the full treatment schedule; 53 (93%) received full-dose radiotherapy, while 48 (84%) were given at least 75% of the planned chemotherapy doses. Severe mucositis (World Health Organization [WHO]) grade 3 to 4 was the limiting toxicity and was seen in 79% of patients. The median time for mucositis resolution was 8 weeks. Other toxicities were generally manageable, but there were four treatment related deaths (7%). Fifty patients were assessable for activity, with an overall response rate of 70% (95% confidence interval [CI], 58% to 82%). Complete response (CR) and partial response (PR) rates were 42% and 28%, respectively. CONCLUSION This simultaneous combined-modality regimen was feasible at the cost of severe mucosal toxicity, which required hospitalization with nutritional, parenteral, and hydroelectrolytic support. The high response rate achieved (70%) did not translate into improved survival, probably due to patient eligibility. The likelihood of cure of this high-tumoral-volume patient population remains low (approximately 10%), despite the association of two therapeutic modalities at full standard therapeutic intensity.

2016 ◽  
Vol 130 (9) ◽  
pp. 833-842 ◽  
Author(s):  
V Noronha ◽  
C Goswami ◽  
S Patil ◽  
A Joshi ◽  
V M Patil ◽  
...  

AbstractBackground:Docetaxel, cisplatin plus 5-fluorouracil is an efficacious induction regimen but is more toxic than cisplatin plus 5-fluorouracil. This study aimed to determine whether docetaxel and cisplatin without 5-fluorouracil maintains efficacy while decreasing toxicity.Methods:A multicenter non-comparative pilot study of locally advanced squamous cell carcinoma of the head and neck was performed. Patients received primary therapy comprising three cycles of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin followed by concurrent chemoradiotherapy. The primary endpoint was the response rate to the docetaxel and cisplatin induction regimen.Results:A total of 26 patients were enrolled: of these, 23 (88.5 per cent) received all three docetaxel and cisplatin cycles. Common grade 3–4 adverse events were febrile neutropenia (19.2 per cent of patients), diarrhoea (19.2 per cent) and non-neutropenic infection (15.4 per cent). The overall response rate to docetaxel and cisplatin induction chemotherapy was 65.4 per cent. A total of 23 patients (88.5 per cent) subsequently received chemoradiotherapy with a median radiotherapy dose of 70 Gy. The response rate to chemoradiotherapy was 73 per cent. At a median follow up of 44 months, the 3-year progression-free survival and overall survival rates were 62 per cent and 69 per cent, respectively.Conclusion:Docetaxel and cisplatin induction chemotherapy is a feasible induction regimen with comparable efficacy to docetaxel, cisplatin and 5-fluorouracil induction chemotherapy.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15520-15520 ◽  
Author(s):  
A. A. Javed ◽  
A. Shaharyar ◽  
I. H. Shah ◽  
M. A. Shah ◽  
T. N. Ansari ◽  
...  

15520 Background: The optimum radiosensitizing dose and schedule of gemcitabine for squamous cell carcinoma of head and neck are not known. The objectives of this study were to evaluate the efficacy and toxicity of weekly gemcitabine as a radiosensitizer concurrent with radical radiotherapy in locally advanced head and neck cancer. Method: Thirty-nine patients with stage III or IV B inoperable carcinoma of head and neck were enrolled. Eligible patients had histopathologically confirmed squamous cell carcinoma with age between 18–70 years. Patients had a KPS >70 with an adequate marrow, hepatic and renal function. No prior chemotherapy or radiotherapy was allowed. Patients with nasopharyngeal, glottic or sub-glottic cancer were excluded. Gemcitabine 150 mg/m2 or a total dose not exceeding 200 mg was given on day 1,8,15,22,29, and 36 during radiation treatment. Gemcitabine was infused in 200 ml of normal saline in 2 hours and radiation was delivered two hours after the completion of gemcitabine infusion. Conventional fractionation was used to deliver a total dose of 66 Gy. CTC version 2.0 of NCI and RTOG/EORTC Late Radiation Morbidity Scoring Scheme were used for evaluation of toxicity and RECIST was used for response evaluation. Results: Only 35 patients were considered evaluable for response. Complete response was seen in 8 (22.9%) (95% CI; 10.4–40.1%), partial response in 25 (71.4%), with an overall response rate of 94.3% (95% CI; 80.8–99.3%). All the thirty-nine patients were evaluable for toxicity. Grade 3 and 4 mucositis was seen in 28 (71.8%) and 2 (5.1%) patients respectively. Grade 3 pharyngeal toxicity was seen in 6 (15.4%). One patient developed pharyngo-cutaneous fistula. Despite vigorous symptomatic and supportive care acute toxicities led to treatment interruption in 16 (41%) of patients. Conclusion: Weekly gemcitabine at a dose of 150mg/m2 concurrent with radiation therapy gives a high overall response rate and a high rate of acute toxicity. No significant financial relationships to disclose.


2014 ◽  
Vol 03 (03) ◽  
pp. 154-158 ◽  
Author(s):  
Sayan Paul ◽  
Tamojit Chaudhuri ◽  
M. C. Pant ◽  
D. Parmar ◽  
Kirti Srivastava

Abstract Aims: The aim of the present study is to investigate the association between polymorphism of cytochrome P450 2C9 (CYP2C9) enzyme with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving cisplatin-based radical chemoradiation (CT-RT). Materials and Methods: Four hundred and sixty patients suffering from locally advanced HNSCC and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs) by polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). Each case was assessed thoroughly for treatment response as per the World Health Organization (WHO) criteria. Results and Analysis: The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.8%) and CYP2C9FNx013 (25%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several folds increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (n = 436) carrying variant alleles of CYP2C9FNx012 (69.6%) or CYP2C9FNx013 (65.2%) were found to respond poorly to cisplatin-based radical CT-RT. Conclusion: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment protocol.


2018 ◽  
Vol 07 (03) ◽  
pp. 188-192 ◽  
Author(s):  
Sundaram Subramanian ◽  
Nithya Sridharan ◽  
V. Balasundaram ◽  
Sameer Chaudhari

Abstract Context: Role of nimotuzumab in locally advanced head and neck cancer (HNC) is well established in India; however, no clinical evidence is available for its role in recurrent and/or metastatic HNC. Aims: The aim of this study is to evaluate the efficacy and safety of nimotuzumab when added to standard treatment in unresectable, recurrent, and metastatic squamous cell carcinoma of the head and neck (SCCHN) Settings and Design: Hospital records of 14 patients diagnosed with recurrent and/or metastatic HNC with histologically confirmed squamous cell carcinoma and being treated with nimotuzumab along with standard treatments from December 2010 to December 2016 were retrospectively evaluated. Subjects and Methods: The tumor response rate and overall survival (OS) were analyzed. Toxicity and adverse events (AEs) were assessed as per common terminology criteria for adverse events (CTCAE) v 4. Results: Oral cavity was most commonly involved region followed by hypopharynx and oropharynx. At 24 weeks after completion of treatment, overall response rate (complete response (CR) + partial response (PR)) was 75%. Survival rate at 1, 2, and 3 years was 77.80%, 64.81%, and 64.81%, respectively. At a median follow-up of 15.17 months, median OS was not reached. All AEs were either Grade I (66.7%) or Grade II (33.3%). No Grade III or Grade IV AEs were observed. No added toxicity was observed due to nimotuzumab. Conclusions: In the first of its kind study, the addition of nimotuzumab to standard treatment showed promising response rate as well as survival outcomes in recurrent and/or metastatic SCCHN patients without producing additional toxicity.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17045-e17045
Author(s):  
S. Billan ◽  
R. Abdah-Bortnyak ◽  
F. Mezid ◽  
Z. Bernstein ◽  
E. Gez ◽  
...  

e17045 Background: Encouraging results have recently been reported in patients with locally advanced squamous cell carcinoma of the head and neck. The present study assessed the feasibility of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CHT-RT) or concurrent cetuximab-radiotherapy. Methods: Induction chemotherapy consisted of TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), 5-fluorouracil 750 mg/m(2)/d continuous infusion for 96 h) every three weeks, followed by CHT-RT regimen (radiotherapy 70 Gy total dose fractionated at 2Gy per day, 5 days a week concurrently with weekly cisplatin 40 mg/m(2) or cetuximab with loading dose of 400 one week before starting radiotherapy and 250 weekly during the radiotherapy) 4–7 weeks later. Percutaneus endoscopic gastrectomy inserted before the combined treatment. The National Cancer Institute Common Toxicity Criteria (version 2) were used for classification of adverse events. Results: Between march 2007 and november 2008, 29 previously untreated patients (19 male and 4 female) with stage III-IV squamous cell carcinoma of the oral cavity, larynx, oropharynx, or hypopharynx were included to the study. The median age was 60 years (range, 56–75 years). The stage distribution was as follows: stage II, 1 patient; stage III, 14 patients; and stage IV, 14 patients. 16 patients had a performance status of 0 and 11 had a performance status of 1. The response rate (RR) after IC was: complete response (CR) for 10 pts (34%), partial response (PR) for 13 pts (57%) and no response (NR) for 3 pts (13%). Toxicity from IC included neutropenia Gr III,IV 25%,neutropenic fever 9%, mucositis and diarrhrea Gr III, IV 22% . 60% of patients completed 3 cycles, 20% received 2 cycles and 20% received only one cycle of TPF. The toxicity from the concurrent phase included mucositis Gr III-IV in 70% of patients,dermatitis Gr III-IV in 43% and no case of neutropenia Gr III-IV. The combined treatment was interrupted only in 4 patients for one week. Conclusions: TPF was well tolerated with high response rate and low rate of acute toxicity. Three cycles of TPF followed by combined treatment are feasible. No significant financial relationships to disclose.


2019 ◽  
Vol 20 (21) ◽  
pp. 5399 ◽  
Author(s):  
Valerie Cristina ◽  
Ruth Gabriela Herrera-Gómez ◽  
Petr Szturz ◽  
Vittoria Espeli ◽  
Marco Siano

Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Nearly 10 years after the approval of cetuximab, anti-PD1/PD-L1 checkpoint inhibitors are the first drugs that have shown any survival benefit for the treatment on platinum-refractory recurrent/metastatic (R/M) HNSCC. Furthermore, checkpoint inhibitors are better tolerated than chemotherapy. The state of the art in the treatment of R/M HNSCC is changing, thanks to improved results for checkpoint inhibitors. Results for these treatments are also awaited in curative settings and for locally advanced HNSCC. Unfortunately, the response rate of immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit the most from immunotherapy. Furthermore, the combination of checkpoint inhibitors with various agents is being currently evaluated to improve the response rate, prolong response duration, and even increase the chances for a cure. In this review, we summarize the most important results regarding immune targeting agents for HNSCC, predictive biomarkers for resistance to immune therapies, and future perspectives.


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