scholarly journals Induction Chemotherapy with Docetaxel, Cisplatin and 5-Fluorouracil (TPF) Followed by Chemoradiotherapy for Locally Advanced Head and Neck Cancer: Can It Achieve Its Potential?

2020 ◽  
pp. 1-10
Author(s):  
Nicholas P Rowell ◽  
Nicholas P Rowell

Objective: In view of concerns about toxicity and deliverability of induction chemotherapy and its impact on subsequent chemoradiotherapy, a retrospective review was carried out with patients treated for locally advanced head and neck cancer (LAHNC) in a single centre between 2007-2017. Patients and Interventions: Patients with LAHNC and good performance status receiving induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) followed by chemoradiotherapy to 70Gy in 35 daily fractions with platinum-based chemotherapy. Main Outcome Measures: Overall and cause-specific survival, rates of locoregional recurrence or distant metastasis, treatment-related toxicity. Results: One hundred and eight patients with LAHNC were treated with 1-4 cycles of TPF (95 receiving two cycles) followed by chemoradiotherapy. The mean delivered dose intensity was 97.6% for all TPF cycles. Median interval from the start of the final cycle of TPF to the start of radiotherapy was 24 days, with 92/103 (89%) starting radiotherapy within 28 days. Median radiation treatment time was 47 days. The mean delivered dose intensity for chemotherapy delivered concurrently with radiotherapy was 97%. There were significantly fewer dose reductions in those receiving platinum/5FU combinations than platinum only regimes (P < 0.0001). For those receiving two cycles of TPF, 90% of patients completed the whole course of treatment within 14 weeks (median overall treatment time 13.1 weeks). There were four treatment-related deaths during induction chemotherapy and none during radiotherapy. Twenty-five developed locoregional failure and 13 distant metastases (both in eight). Actuarial overall survival was 60.7% at five years, with progression-free survival of 77.9% at two years and 74.1% at five years. For oropharynx cancers, overall survival was 70.4% and progression-free survival 80.8% at five years. Conclusion: Although significant toxicity from TPF was observed, with appropriate support, it is possible to complete treatment without undue compromise of subsequent treatment.

2018 ◽  
Vol 36 (11) ◽  
pp. 1064-1072 ◽  
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vijay Maruti Patil ◽  
Jaiprakash Agarwal ◽  
Sarbani Ghosh-Laskar ◽  
...  

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.


2005 ◽  
Vol 23 (10) ◽  
pp. 2310-2317 ◽  
Author(s):  
Michael Stahl ◽  
Martin Stuschke ◽  
Nils Lehmann ◽  
Hans-Joachim Meyer ◽  
Martin K. Walz ◽  
...  

Purpose Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy is unknown. Patients and Methods Patients with locally advanced squamous cell carcinoma (SCC) of the esophagus were randomly allocated to either induction chemotherapy followed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery (arm B). Primary outcome was overall survival time. Results The median observation time was 6 years. The analysis of 172 eligible, randomized patients (86 patients per arm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in the surgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) than in the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI, 28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003). Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001). Conclusion Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC. Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients, regardless of the treatment group.


2021 ◽  
pp. 38-38
Author(s):  
Bojan Radojicic ◽  
Marija Radojicic ◽  
Miroslav Misovic ◽  
Dejan Kostic

Background/Aim. About 1.8 million new lung cancer cases are diagnosed in the world every year, and about 1.6 million cases are with fatal outcome. Despite improvements in treatment in previous decades, the survival of patients with lung cancer is still poor. The five-year survival rate is about 50% for patients with localized disease, 20% for patients with regionally advanced disease, 2% for patients with metastatic disease, and about 14% for all stages. The median survival of patients with untreated NSCLC in the advanced stage is four to five months and the annual survival rate is only 10%. The main goal of the research is to obtain and analyze the results of treatment with concomitant chemotherapy in terms of its efficacy and toxicity in selected patients with locally advanced inoperable non-small cell lung cancer. Methods. The study included data analysis of 31 patients of both sexes who were diagnosed and pathohistologically verified with NSCLC in inoperable stage III and were referred by the Council for Malignant Lung Diseases to the Radiotherapy Department of the Military Medical Academy for concomitant chemoradiotherapy treatment. Upon expiry of the three-month period from the performed radiation treatment, the tumor resonance was assessed on the basis of MSCT examination of the chest and upper abdomen according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). According to the same criteria, progression-free survival (PFS) was also assessed every three months during the first two years, then every 6 months or until the onset of disease symptoms, as well as overall survival (OS). Result. The median progression-free survival is 13 months, and the median overall survival is 20 months. During and immediately after RT, 9 (29%) patients had a grade 2 or higher adverse event. Conclusion. The use of concomitant chemoradiotherapy in patients in the third stage of locally advanced inoperable non-small cell lung cancer provides a good opportunity for a favorable therapeutic outcome, with an acceptable degree of acute and late toxicity, and represents the standard therapeutic approach for selected patients in this stage of the disease.


2018 ◽  
Vol 25 (6) ◽  
pp. 1301-1304 ◽  
Author(s):  
Mário L de Lemos ◽  
Isabell Kang ◽  
Kimberly Schaff

Background Patients with locally advanced, recurrent or metastatic solitary fibrous tumour are often treated with bevacizumab and temozolomide based on the clinical efficacy reported in a case series of 14 patients. Given the rarity of solitary fibrous tumour, large trials are not feasible. We report the efficacy of this regimen based on a population-based analysis. Methods This was a population-based retrospective, multi-centre analysis using patient data from a provincial cancer registry and treatment database. Cases from June 2006 through October 2016 were identified for patients receiving bevacizumab and temozolomide for locally advanced, recurrent or metastatic solitary fibrous tumour or hemangiopericytoma, which is sometimes used to describe tumours arising from the meninges. The primary outcome was overall response rate. Secondary outcomes included time to response, progression free survival and overall survival estimated using the Kaplan–Meier method. Results Fourteen patients were identified: median age 59 (range 44–70), male 78.6%. Diagnoses were solitary fibrous tumour in 10 (71.4%) and hemangiopericytoma in four (28.6%), with metastatic disease in 10 (72.7%) patients. The most common primary sites were meninges in four (28.6%) and pelvis in three (21.4%) patients. The median follow-up was 15.5 months, with median treatment of four months. Overall response rate was 21.4% (no complete response, 3 partial response), with median time to response of four months. Median progression free survival, six-month progression free survival and overall survival were 17 months, 65.0%, and 45 months, respectively. Conclusions Efficacy of bevacizumab and temozolomide in solitary fibrous tumour appeared to be similar to that previously reported. Our findings confirmed that bevacizumab and temozolomide is an effective and tolerated treatment for this patient population.


2017 ◽  
Vol 17 (1) ◽  
pp. 124-130
Author(s):  
Ekkasit Tharavichitkul ◽  
Panupat Rugpong ◽  
Nisa Chawapun ◽  
Razvan M. Galalae

AbstractPurposeThis study aims to clarify the influence of overall treatment time (OTT) on the efficiency of combined chemo-radiotherapy in cervical cancer.Material and methodsThis retrospective study enrolled 122 cervical cancer patients who had squamous cell carcinoma and had undergone definitive chemo-radiotherapy from 2009 to 2013. All patients received whole pelvic radiotherapy (WPRT) with the dose of 50 Gy in 25 fractions (with central shielding after 44 Gy) plus intracavitary brachytherapy with the dose of 28 Gy in four fractions. During WPRT, all patients received concurrent chemotherapy with weekly platinum-based regimen. The data of patient characteristics, OTT, treatment results and toxicities were collected and evaluated.ResultsThe mean follow-up time was 36 months. The mean age of patients was 52 years old; 68% of patients were stage IIB related to International Federation of Gynaecology and Obstetrics staging. Pelvic control (PC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) rates did not differ significantly in the data-derived cut points of 55·8 and 53 days. No statistically significant difference in treatment results between the two groups of OTT<49 and OTT≥62 days was observed.ConclusionsIn our data-derived cut point, OTT did not influence to PC, DMFS, DFS and OS. The influence of OTT on treatment results may be found in longer periods.


2021 ◽  
pp. 030089162110390
Author(s):  
Che-Wei Su ◽  
Jehn-Chuan Lee ◽  
Yi-Fang Chang ◽  
Nai-Wen Su ◽  
Pei-Hsuan Lee ◽  
...  

Introduction: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC. Methods: From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score). Results: A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<–0.16) was associated with improved PFS ( p < 0.05). Conclusions: The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Dr/Khaled Abdel Karim ◽  
Dr/Khaled Nagib ◽  
Dr/Ahmed Hassan Abd El Aziz ◽  
Christina Gamil Garas

Abstract Background Lung cancer is the leading cause of cancer death worldwide, but little is known about how patients with this disease are managed. Aim of the Work We aim to study patterns of care and treatment pathways of non- surgically managed early and locally advanced NSCLC patients from January 2015 to December 2018 in Ain Shams University Clinical Oncology Department. Patients and Methods In this retrospective analysis we included patients the met the following criteria; age &gt;18, histologically confirmed NSCLC patients whom didn’t undergo surgical resection with at least 6 months of follow up data. We collected data from Clinical Oncology department archive in Ain Shams university hospital. Our primary objective is to identify the patterns of care and treatment pathway for non surgically managed NSCLC patients in ASUCOD from January 2015 to December 2018. Results 86 patients finally met our inclusion criteria. Median age at diagnosis of 61 years with a range of (38-85), 95.3% were male. Most of the patients were stage III; 40.7% were stage IIIA, 41.9% were stage IIIB, and 9.3% were stage IIIC. 41 were treated radically, 37 received palliative treatment and only 8 patients received supportive care. Overall median progression free survival in our patients was 9.23 (7.4-13.5) and overall survival duration was13.4 (9.5-18.0). In radically treated patients, 68.3% received sequential chemoradiotherapy (sCRT), 29.2% received concurrent chemoradiotherapy (cCRT) or 2.4% received definitive radiotherapy alone (RT). In palliative treated patients, 73% received chemotherapy alone (CTX), 8.1% received palliative RT and 18.9% received both chemotherapy and palliative dose of radiotherapy (CRT). All treatment modalities were similar regarding median progression free survival and overall survival durations, 17.5 (3.6–19.6) and 20.6 (3.6–31.6) in cCRT, 17.5 (3.6–19.6) and 23.3 (17.7–31.2) in sCRT, 12.9 and 13.4 RT group, P value=0.57 and 0.16 receptively. Similarly, progression free survival and overall survival durations were 8.8 (3.0–15.8) and 16.2 (3.6–18.7) in CRT, 5.3 (0.4–7.6) and 8.6 (6.2–10.2) in CTX, 8.5 (0.4–8.5) and 8.5 (0.4–8.5) in palliative RT group, P value=0.64 and 0.15 receptively. In our study, first-line chemotherapy were Gemcitabine plus Cisplatin (41.9%) or Carboplatin (35.1%).The Second -line chemotherapy were Docetaxel (63.1%) or Paclitaxel plus Carboplatin (26.3%). Paclitaxel plus Carboplatin were the most regimen given with RT. Most of the patients received radiation dose of 60Gy/30Fr (73.2%). Regarding the incidence of toxicity, there were significant high rates of esophagitis in cCRT in grade 3 or more compared to sCRT. Conclusion We have found that less than half of this study population were treated radically while the other half received palliative treatment. And only few patients received best supportive care. Radically treated patients had higher progression free survival and overall survival durations compared to palliative and supportive treatment.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sylvie Lorenzen ◽  
Alexander Biederstädt ◽  
Ulrich Ronellenfitsch ◽  
Christoph Reißfelder ◽  
Stefan Mönig ◽  
...  

Abstract Background Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted. Methods The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life. Discussion The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone. Trial registration ClinicalTrials.gov; NCT04375605; Registered 4th May 2020;


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