Phase II study of gemcitabine concurrent with radiation in locally advanced squamous cell carcinoma of head and neck: Trial of the Cancer Research Group Pakistan

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.

2017 ◽  
Vol 35 (14) ◽  
pp. 1542-1549 ◽  
Author(s):  
Joshua Bauml ◽  
Tanguy Y. Seiwert ◽  
David G. Pfister ◽  
Francis Worden ◽  
Stephen V. Liu ◽  
...  

Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti–programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. Results Among 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade ≥ 3 event. Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. Conclusion Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  

Abstract Background This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. Results A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). Conclusion CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.


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.


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.


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.


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.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4073-4073
Author(s):  
Jinming Yu ◽  
Xue Meng ◽  
Jian hua Wang ◽  
Xindong Sun ◽  
Lv hua Wang ◽  
...  

4073 Background: In China more than 90% of esophageal malignancies are of squamous cell carcinoma (SCC). We conducted this Chinese multicenter trial to determine the efficacy and safety of the addition of cetuximab with paclitaxel, cisplatin, and concurrent radiation for patients with esophageal SCC and to determine whether KRAS status predicts response. Methods: Patients with unresectable locally advanced cervical, upper or mid-esophageal SCC without distant metastasis were eligible for this open-label phase II trial. All patients received cetuximab (400 mg/m2 day 1 before chemoradiotherapy and 250 mg/m2 q1w × 7 weeks), paclitaxel (45 mg/m2 q1w × 7 weeks) and cisplatin (20 mg/m2 q1w × 7 weeks) with 59.4 Gy of radiation. The primary end point was response rate. Second end points included toxicity, overall survival (OS), progression-free survival (PFS), and KRAS mutation status. Results: Fifty-five patients were enrolled and evaluable to safety. Non-hematological adverse events were generally grade 1 or 2, and were most often rash (94.5%), mucositis (58.2%), fatigue (45.5%), nausea (41.8%) and hepatic dyfunction (40%). Hematologic adverse events included grade 3 neutropenia (32.7%) and grade 3 anemia (1.82%). Ten patients did not complete the protocol therapy (6 for chemotherapy dose delays, 1 for paciltaxel hypersensitivity, 1 by the treating physicians for unstated reasons, 1 for concurrent unrelated infection, and 1 for tracheo-esophageal fistula). The response rate was 97.7%. The 1-year OS and median OS was 87.3% and 16.8 months, the 1-year PFS and median PFS was 30.4% and 13.9 months, respectively. No mutations were detected at KRAS codons 12 or 13 in the 52 available specimens. Conclusions: Cetuximab can be safely administered with chemoradiation for Chinese patients with esophageal cancer and may improve the clinical response rate. KRAS mutations were too rare to be analyzed as a predictor of response.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16055-e16055
Author(s):  
Alexandre Bozec ◽  
Nicolas Fakhry ◽  
Charlotte Dupuis ◽  
Benjamin Lallemant ◽  
Marc Alfonsi ◽  
...  

e16055 Background: Phase III studies have demonstrated that induction chemotherapy with TPF followed by cisplatin-based chemoradiation (CRT) is a valid option for the treatment of advanced unresectable head and neck squamous cell carcinoma. These studies have been done in highly selected patients. The aim of our study is to confirm these data in unselected patients and to identify prognostic factors of tolerance and survival. Methods: Between October 2005 and June 2010, 300 patients from 5 institutions with locally advanced neck and head cancer received at least one induction cycle, followed by locoregional radiotherapy (R) associated or not with platinum (P) or cetuximab (C)-based chemotherapy. Results: Mean age was 56 years old (range 31-76). Performance status was 0 or 1 in 97% of patients and 50 % of them presented current alcohol intoxication. 69% (n=208) received 3 cycles of TPF, and 91% (n=268) underwent R associated or not with P (n=167) or C (n=51). 52% of patients (n=156) received the conform treatment (ie 3TPF + RP or RC). Grade 3-4 toxicities have been reported in 19% (n= 57), including 3% febrile neutropenia (n=9) and 7% kidney failure (n=22). Grade 3-4 toxicity, during TPF induction, led systematically to permanently discontinuation of the chemotherapy. Overall response rate after TPF induction was of 88% with 23% of complete response. After a median follow-up of 21 months, median progression-free survival and cause-specific survival (SS) were not reached. Median overall survival (OS) was 49 months (95% CI 31.2-66.8). SS and OS were significantly improved (p<0.0001) in patients who received the conform treatment. In multivariate analysis the probability of death related to cancer or to toxicities induced by treatment was increased for hemoglobin level ≤ 12.6g/dl or GGT level ≥ 77U/I [HR = 3.45 (95% CI: 1.50-7.93) p=0.0029]. Conclusions: We propose to use a biological index based on baseline hemoglobin and GGT levels to select patient for induction therapy in SCCHN. This simple index, predictive of treatment conformity and specific survival, needs further prospectives investigations.


KYAMC Journal ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 128-132
Author(s):  
Md Nazmul Alam ◽  
Md Abdul Bari ◽  
Sarwar Alam ◽  
Md Shahidul Islam ◽  
Tanvir Ahmed

Background: Radiotherapy and chemotherapy are practiced widely for the treatment of locally advanced squamous cell carcinoma of head and neck Objectives: To compares the effectiveness and toxicities between induction chemotherapy followed by radiotherapy alone and concurrent chemoradiotherapy Materials and Methods: A quasi experimental study was carried out from January 2014 to December 2014. Total sixty patients with locally advanced squamous cell carcinoma of head and neck origin were included and allocated into the arm A and B alternatively. Induction chemotherapy by Cisplatin and 5-Fluorouracil was given to the patient of both arms. Injection Cisplatin was given concurrently during the whole length of radiotherapy period in Arm A while patient in Arm B received radiotherapy alone. The patients were evaluated up to 30 weeks following the completion of the treatment. Results: In this study, male to female ratio was 4:1 and mean age at diagnosis was 60 ± 5 years. Overall complete response was 90% (27/30) and 53.3% (16/30) for the Arm A and Arm B respectively at 30 weeks after completion of treatment. During induction chemotherapy only 5% (3/60) of patients suffered from Grade 3 diarrhoea in both arms. In Arm A Grade 3 and 4 mucositis was observed in 36.66% (11/30) and 3.33% (1/30) of patients respectively whereas in Arm B it was 33.33% (10/30) and 3.33% (1/30) respectively. Conclusion: Induction chemotherapy followed by concurrent chemoradiotherapy is more effective than induction chemotherapy followed by radiotherapy alone in loco-regional control of locally advanced squamous cell carcinoma ofhead and neck origin KYAMC Journal Vol. 10, No.-3, October 2019, Page 128-132


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