A Prospective Randomised Trial Comparing Neoadjuvant Chemotherapy Followed by Concomitant Chemoradiation versus Concomitant Chemoradiation Alone in Locally Advanced Inoperable Head and Neck Squamous Cell Carcinoma (original) (raw)
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Radiotherapy and Oncology, 2011
We retrospectively reviewed acute toxicity with cetuximab and radiotherapy, comparing it with a matched cisplatin group. The cetuximab group experienced significantly more toxicity -grade P3 oral mucositis (p = 0.014), skin dermatitis (p = 0.0004), P10% weight loss (p = 0.03), and enteral feeding requirement (p = 0.05). This finding of enhanced toxicity is similar to recent publications. Ó This is the first large community experience comparing tolerability and toxicity of cetuximab (CTX) and radiotherapy (RT), with the hitherto conventional approach of RT and cisplatin (CDDP).
International Journal of Radiation Oncology*Biology*Physics, 2007
To assess the feasibility and efficacy of accelerated weekly 6 fractionated 66-Gy postoperative radiation therapy (PORT) using a single fraction regimen from Monday to Thursday and a concomitant boost in the Friday afternoon sessions combined with concomitant cisplatin chemotherapy (CT) in patients with locally-advanced head and neck cancer (LAHNC). Materials/Methods: Between March 2001 and April 2006, 40 (male to female ratio: 35/5; median age: 60 years [range: 36-81]) patients with pT1-pT4 and/or pN0-pN3 LAHNC (15 oral cavity, 8 oropharynx, 8 hypopharynx, 7 larynx, and 2 unknown primary) were included in this pilot study. Indications of PORT/CT were positive surgical margins (n = 9; all R1), T4 R0 tumors (n = 5), 3 or more positive lymph nodes without extranodal infiltration (all R0; n = 2) in 16 (40%) patients; or extranodal infiltration with (all R1; n = 13) or without (n = 11) positive surgical margins in 24 (60%) patients. Median interval between surgery and RT was 46 days (range: 24-112). RT consisted of 66 Gy (2 Gy/fr) in 5.5 weeks. Median RT duration was 39 days (range: 35-62). Five-field 3D conformal or intensity-modulated RT was performed in all patients according to the GORTEC/EORTC/RTOG guidelines. Concomitant cisplatin chemotherapy was planned at 100 mg/m 2 in days 1, 22, and 43 in all but one patient where carboplatin was chosen due to impaired renal function. Prophylactic percutaneous endoscopic gastrostomy was performed in 18 (45%) patients, and 3 (8%) patients required nasogastric feeding tube. Median follow-up was 37 months (range: 5-66). Results: All but two patients received the planned total dose without unplanned interruption (66 Gy in 38, 64 Gy in 1, and 58 Gy in 1). According to the CTC/NCI v3.0 toxicity criteria, acute morbidity was acceptable: grade 3 mucositis in 10 (25%), grade 3 dysphagia in 9 (23%), grade 3 skin erythema in 5 (13%) patients. CT-related anemia was observed in 2 patients (grade 3 in 1, and grade 4 in 1), leukopenia in 4 patients (grade 3 in 2, and grade 4 in 2), and no grade 3 or 4 thrombocytopenia was observed. Grade 3 renal-function impairment was observed only in one patient. Median weight loss was 3.5 kg (range: 0-14.5). No treatmentrelated mortality was observed. Considering the late effects, grade 0, 1, or 2 xerostomia was observed in 9 (23%), 22 (55%), and 9 (23%) patients, respectively; grade 0, 1, and 2 edema in 25 (63%), 14 (35%), and 1 (3%) patients, respectively. Locoregional relapse was observed in 8 (20%) patients, and only 7 (18%) patients developed distant metastases. Median time to locoregional relapse was 6 months (range: 1-40). The 3-year overall, cause-specific, disease-free survival, and locoregional control rates were 65%, 69%, 64%, and 82%, respectively. Distant metastasis probability at 3 and 5 years was 19%. Univariate and multivariate analyses revealed that the only prognostic factor influencing the outcome was nodal status. Conclusions: We conclude that reducing the overall treatment time using accelerated PORT/CT by weekly concomitant boost (6 fractions per week) combined to concomitant cisplatin chemotherapy is easily feasible with good locoregional and distant metastases control for patients operated with curative intent for LAHNC. Acute and late RT/CT-related morbidity is acceptable.
Radiotherapy and Oncology, 2010
Background and purpose: Induction chemotherapy prior to definitive concurrent chemoradiotherapy (CCRT) is a promising treatment option for unresectable head and neck cancer (HNC). In the postoperative setting, the efficacy of such an approach with adjuvant chemotherapy (AdjCT) followed by postoperative CCRT is unclear. Materials and methods: Forty-one postoperative patients with stage III-IV (M0) HNC enrolled on 3 consecutive phase II clinical trials were retrospectively analyzed. Twenty-five of the patients were treated on a protocol which included AdjCT with carboplatin and paclitaxel prior to postoperative CCRT (AdjCT group). Sixteen were treated on protocols with similar postoperative CCRT but without AdjCT (control group). CCRT consisted of paclitaxel, 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy. Results: After a median follow-up of 72 months, there were no locoregional failures (LRF) or distant metastases (DM) in the AdjCT group. In the control group, there were 2 LRF and 2 DM. The 5-year risk of disease recurrence was 0% in the AdjCT group, compared to 28.9% in the control group (p = 0.0074). No patients had disease progression during AdjCT, and all proceeded to postoperative CCRT without delay. Conclusions: Adjuvant chemotherapy after surgery followed by CCRT may be a treatment strategy associated with favorable disease outcomes in locoregionally advanced HNC. These results pose a hypothesis which warrants further investigation. Ó
Journal of Xiangya Medicine, 2021
Background: Concurrent chemoradiotherapy is the mainstay of treatment in locally advanced head and neck cancer (LAHNC). Several studies have shown better outcome with altered fractionation radiation schedules, especially with hyperfractionation (HF-RT). For the last few decades attempts are being done to combine altered fractionation regimens with concurrent chemotherapy to achieve higher therapeutic gain. This study was done to evaluate the efficacy and toxicity of hyperfractionated concurrent chemoradiation (HF-CRT) in comparison to conventional concurrent chemoradiotherapy (CF-CRT). Methods: This was a prospective trial registered with Clinical Trials Registry-India (REF/2022/01/050552), randomizing LAHNC patients into control group (CF-CRT) (70 Gy/35 fractions/5 fractions per week, 2 Gy/fraction/day) or study group (HF-CRT) (81.6 Gy/68 fractions/10 fractions per week, 1.2 Gy/fraction, twice daily at 6 hours interval). Concurrent chemotherapy consisted of weekly cisplatin (40 mg/m 2). The primary and secondary endpoints were response to therapy and treatment-induced toxicity respectively. Results: A total of 214 eligible patients were recruited: 106 patients in control group & 108 patients in study group. Median follow-up was 7 months. Median overall treatment time was 59 & 63 days in control & study groups respectively. Complete response rates at primary and nodal sites were statistically similar (64% vs. 74%; P=0.1 and 54% vs. 61%; P=0.3 for CF-CRT & HF-CRT respectively). For objective response rate (ORR) and late toxicity rate, again there was no significant difference between the two radiation protocols. However, HF-CRT was associated with significantly higher rate of severe acute mucositis. Conclusions: Combining HF-RT with concurrent chemotherapy did not provide any significant gain in response rate, rather it was associated with higher acute toxicity, inconvenience and logistic issues giving CF-CRT a practical advantage over this protocol especially in resource-restrained settings.
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.
International Journal of Research in Medical Sciences, 2014
varying degree of functional and cosmetic deformity that are often exacerbated by cancer treatment. Larynx preservation trial 1991, 1 the non-surgical organ preservation through the radiation and chemotherapy entered the main stream. Since then the most significant advances in the treatment of head and neck tumours have been the development of altered fractionation schedules ABSTRACT Background: Objective of current study was to observe the local control, progression free survival and organ preservation for locally advanced head and neck cancer by using induction Chemotherapy followed by concurrent chemoradiotherapy. Methods: 102 patients enrolled in this study with stage III-IVB of head & neck cancer. Patients were assessed and treated by faculty of the department as per NCCN guidelines. Group A patients received three courses of cisplatin (100mg/m 2) and paclitaxel (175mg/m 2) at every 21 days interval followed by concurrent chemoradiothearpy with cisplatin 30mg/m 2 on weekly basis while group B received only concurrent chemoradiothearpy. Radiotherapy consisted of total dose up to 66-70 Gy. by conventional fractionation schedule. Results: From August 2011 to July 2013, total 102 patients have completed 14 months of follow up after completing definitive treatment group A : 48 and group B: 54 patients. Response evaluation was done after one and half months of completion of chemoradiotherapy in both arms. Complete response rate was 60.42% and 38.88 % in study and control arm respectively while partial response was 72.92% and 55.56%. Most common grade III or IV toxicity was mucositis in group A and skin reaction in control arm. At a median follow-up 13 months the median progression free survival in group A was 11.5 months and 9 months in group B. Conclusion: Response to induction chemotherapy was useful as predictive factor for ultimate outcome and progression free survival. But our study shows statistically significant improvement in complete response rate in group A as compared to group B (p<0.05). Our induction chemotherapy with two-drug regimen followed by concurrent chemoradiotherapy was well tolerated with manageable toxicity and good locoregional control.
Cancer, 2000
BACKGROUND. Combined modality therapy plays a central role in the management of advanced head and neck tumors. The objective of our Phase II study was to determine the feasibility, toxicity, and clinical and pathologic response of preoperative induction chemotherapy, followed by concurrent chemoradiotherapy in patients with Stage III or IV squamous cell carcinoma according to the American Joint Committee on Cancer Staging of the oral cavity and oropharynx with no distant metastases. METHODS. After staging, 62 patients with locally advanced carcinoma of the oral cavity and oropharynx were treated preoperatively with chemotherapy (1 cycle of cisplatin and 5-fluorouracil [P-5FU]) followed by concurrent chemoradiotherapy (3 cycles of P-5FU combined with radiotherapy, 60 grays [Gy] given in 33 fractions of 1.8 Gy). After evaluation, patients underwent surgery either as a diagnostic (biopsy) or therapeutic procedure (resection of the primary tumor and/or the neck). Surgery was performed with the intent to spare organ function. RESULTS. Grade 3-4 mucositis was observed in 37 patients (59%). Overall clinical response was obtained in 87%, and the complete clinical response rate was 50%. Surgery was performed in 53 patients, 50 at the primary tumor site (11 biopsies, 14 marginal excisions, and 25 wide excision) and 46 patients had neck dissection. Pathologic complete remission was observed in 29 patients (46%). After a median follow-up of 39 months, locoregional control rate was 76%, estimated 3-year disease free survival rate was 73% (Ϯ 4%), and estimated 3-year overall survival rate was 76% (Ϯ 4%). CONCLUSIONS. This intensive multimodality treatment is feasible, and toxicity is significant but tolerable. The treatment results appear promising and durable. Organ-preserving surgery can be performed in many patients. Cancer 2000;89: 939-45.