A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer (original) (raw)
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Annals of Oncology, 2010
Background: Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. Patients and methods: Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m 2 , days1-4, plus 5-fluorouracil 800 mg/m 2 /day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m 2 and cisplatin 80 mg/m 2 , day 1, and 5-fluorouracil 800 mg/m 2 /day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. Results: A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. Conclusion: Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.
https://www.ijrrjournal.com/IJRR\_Vol.6\_Issue.11\_Nov2019/Abstract\_IJRR0058.html, 2019
Introduction: Concurrent chemoradiation is currently the standard of care in LAHNSCC. Neoadjuvant Chemotherapy (NACT) causes tumour down staging, facilitating organ preservation and has potential to prevent distant metastasis albeit at the cost of increased toxicities. However potential benefit of adding NACT before CTRT in LAHNSCC still remains unclear. Aims and Objectives: This study compared NACT followed by CTRT versus CTRT alone in LAHNSCC in terms of Locoregional response (LRR), Toxicities and Progression Free Survival (PFS). Materials and method: Patients with LAHNSCC of oral cavity, oropharynx, larynx & hypopharynx (AJCC Stage III-IVB), recruited from January 2013 to January 2015 were randomised into two arms (90 each) to receive either NACT (Paclitaxel 175mg/m 2 and Carboplatin AUC 5 q 3 weeks 3 cycles) followed by CTRT (Arm A) or CTRT alone (Arm B). EBRT dose was 66-70 Gy in conventional fractionation with three weekly Inj. Cisplatin 100 mg/m 2. Results: Median follow up period was 37 months. After NACT, 58.9% of patients achieved PR and CR 7.8%. Response 4 months after treatment showed LRR 56/65 in arm A vs. 53/71 in arm B. Median PFS was 48 months in Arm A vs. 42 months in Arm B; log rank p=0.176. Grade ≥ 3 acute toxicities included myalgia (10%), neutropenia (4.4 %), thrombocytopenia(3.3%) and anemia (3.3%) during NACT. During CTRT more haematotoxicities and mucositis in arm A whereas dermatitis and dysphagia were more in arm B. Regarding late toxicities, grade ≥ 3 neuropathy seen in Arm A. Conclusion: NACT before CTRT is feasible and may be used in LAHNSCC to downstage tumour with no significantly added toxicity.
Lancet Oncology, 2010
Background Between 1990 and 2000, we examined the eff ect of timing of non-platinum chemotherapy when combined with radiotherapy. We aimed to determine whether giving chemotherapy concurrently with radiotherapy or as maintenance therapy, or both, aff ected clinical outcome. Here we report survival and recurrence after 10 years of follow-up. Methods Between Jan 15, 1990, and June 20, 2000, 966 patients were recruited from 34 centres in the UK and two centres from Malta and Turkey. Patients with locally advanced head and neck cancer, and who had not previously undergone surgery, were randomly assigned to one of four groups in a 3:2:2:2 ratio, stratifi ed by centre and chemotherapy regimen: radical radiotherapy alone (n=233); radiotherapy with two courses of chemotherapy given simultaneously on days 1 and 14 of radiotherapy (SIM alone; n=166); or 14 and 28 days after completing radiotherapy (SUB alone, n=160); or both (SIM+SUB; n=154). Chemotherapy was either methotrexate alone, or vincristine, bleomycin, methotrexate, and fl uorouracil. Patients who had previously undergone radical surgery to remove their tumour were only randomised to radiotherapy alone (n=135) or SIM alone (n=118), in a 3:2 ratio. The primary endpoints were overall survival (from randomisation), and event-free survival (EFS; recurrence, new tumour, or death; whichever occurred fi rst) among patients who were disease-free 6 months after randomisation. Analyses were by intention to treat. This trial is registered at www.Clinicaltrials.gov, number NCT00002476. Findings All 966 patients were included in the analyses. Among patients who did not undergo surgery, the median overall survival was 2•6 years (99% CI 1•9-4•2) in the radiotherapy alone group, 4•7 (2•6-7•8) years in the SIM alone group, 2•3 (1•6-3•5) years in the SUB alone group, and 2•7 (1•6-4•7) years in the SIM+SUB group (p=0•10). The corresponding median EFS were 1•0 (0•7-1•4), 2•2 (1•1-6•0), 1•0 (0•6-1•5), and 1•0 (0•6-2•0) years (p=0•005), respectively. For every 100 patients given SIM alone, there are 11 fewer EFS events (99% CI 1-21), compared with 100 given radiotherapy, 10 years after treatment. Among the patients who had previously undergone surgery, median overall survival was 5•0 (99% CI 1•8-8•0) and 4•6 (2•2-7•6) years in the radiotherapy alone and SIM alone groups (p=0•70), respectively, with corresponding median EFS of 3•7 (99% CI 1•1-5•9) and 3•0 (1•2-5•6) years (p=0•85), respectively. The percentage of patients who had a signifi cant toxicity during treatment were: 11% (radiotherapy alone, n=25), 28% (SIM alone, n=47), 12% (SUB alone, n=19), and 36% (SIM+SUB, n=55) among patients without previous surgery; and 9% (radiotherapy alone, n=12) and 20% (SIM alone, n=24) among those who had undergone previous surgery. The most common toxicity during treatment was mucositis. The percentage of patients who had a signifi cant toxicity at least 6 months after randomisation were: 6% (radiotherapy alone, n=13), 6% (SIM alone, n=10), 4% (SUB alone, n=7), and 6% (SIM+SUB, n=9) among patients who had no previous surgery; and 7% (radiotherapy alone, n=10) and 11% (SIM alone, n=13) among those who had undergone previous surgery. The most common toxicity 6 months after treatment was xerostomia, but this occurred in 3% or less of patients in each group. Interpretation Concurrent non-platinum chemoradiotherapy reduces recurrences, new tumours, and deaths in patients who have not undergone previous surgery, even 10 years after starting treatment. Chemotherapy given after radiotherapy (with or without concurrent chemotherapy) is ineff ective. Patients who have undergone previous surgery for head and neck cancer do not benefi t from non-platinum chemotherapy.
Oral oncology, 2016
To compare chemoradiation with 100mg/m(2) cisplatin every three weeks to 20mg/m(2) on five days every four weeks for locally advanced squamous cell carcinoma of the head-and-neck (LASCCHN). In 230 patients receiving chemoradiation for LASCCHN, 100mg/m(2) cisplatin every three weeks (N=126) and 20mg/m(2) cisplatin on five days every four weeks (N=104) were retrospectively compared. Chemoradiation plus eleven characteristics (T-/N-classification, performance score, gender, age, tumor site, grading, surgery, radiation technique, pre-chemoradiation hemoglobin, cumulative cisplatin dose) were analyzed for locoregional control (LRC), metastases-free survival (MFS) and overall survival (OS). Chemoradiation groups were compared for adverse events. On univariate analyses, chemoradiation had no impact on LRC (p=0.53), MFS (p=0.67) and OS (p=0.14). On multivariate analysis of LRC, T-classification (p=0.045) and hemoglobin (p<0.001) were significant. On multivariate analysis of MFS, performa...
World Academy of Sciences Journal, 2020
The standard-of-care in locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) remains concurrent chemoradiotherapy. The present study compared the disease response and safety profile of induction chemotherapy followed by concomitant chemoradiotherapy (CRT) vs. CRT alone in patients with LA SCCHN. The present prospective randomized study was conducted between July, 2014 and July, 2015 on 52 patients with SCCHN of the oropharynx, hypopharynx and larynx. Patients were randomly divided into the induction chemotherapy [docetaxel, cisplatin and 5-FU (TPF)] followed by CRT arm (TPF + CRT arm, n=25) or the CRT alone arm (CRT arm, n=27). The disease response, and acute and late toxicities were assessed. At the first follow-up (6 weeks), the overall response rate (ORR) was 82.6% for the TPF + CRT arm and 72% for the CRT arm; the difference was not significant. In addition, no statistically significant differences were observed in the nodal response between the treatment arms. Acute toxicities were significantly higher in the TPF + CRT arm, with respect to mucositis and hematological toxicities. No differences were observed in late-onset toxicities observed following 3 months of radiotherapy. Triple drug-based sequential therapy was tolerable in the population in the present study and may thus hold promise for the treatment of SCCHN; however, larger prospective studies are required to confirm these results.
Medical Oncology, 2017
Many concerns are related to the idea that the acute toxicity of induction chemotherapy (IC) performed with TPF (docetaxel, cisplatin, 5-fluorouracil) could reduce the ability to deliver the subsequent standard concurrent chemoradiotherapy (CRT) in head and neck cancer patients. We performed a critical review of the literature on the toxicity profile of the standard CRT administered after the IC with TPF. A total of 13 papers (including 950 patients) were selected. Results showed that most patients were treated with an adequate radiation total dose although a significant proportion of them (from 15 to 30%) completed the planned treatment with a delay of more than 5 days. A minority of patients were able to be treated with three cycles of concurrent cisplatin, but only few papers reported how many of patients reached the cumulative total dose of almost 200 mg/m 2 cisplatin. The rate of deaths due to treatment-related toxicity varied from 0 to 9% (median and mean 2%). Two prospective trials stopped patient enrollment due to acute treatment-related toxicity and because a low number of patients were able to undergo the planned full schedule of cisplatin during the CRT, respectively. Retrospective analysis of 45 patients treated at our institute showed that this schedule was feasible with manageable side effects. In conclusion, the literature data did not provide homogeneous information on the feasibility of the standard CRT after induction TPF. A more uniform data collection of treatment-related toxicity will be helpful in better selecting the patients who might adequately tolerate this multimodality strategy.