Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00201383
Status:
COMPLETED
Last Update Posted:
2005-09-20
First Post:
2005-09-13
Brief Title:
Post-Operative Adjuvant Concurrent Chemoradiotherapy For High Risk Oral Cavity Squamous Cell Carcinoma Patients
Sponsor:
National Health Research Institutes Taiwan
Organization:
National Health Research Institutes Taiwan
Study Overview
Official Title:
Phase III Study Of Post-Operative Adjuvant Concurrent Chemoradiotherapy For High Risk Oral Cavity Squamous Cell Carcinoma Patients
Status:
COMPLETED
Status Verified Date:
2005-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to confirm the value of concurrent chemoradiotherapy in improving the locoregional control and survival of patients with resected locally advanced HNSCC a phase III randomized study is proposed The population studied in this trial is limited to patients of oral cavity cancer this could reduce the confounding factor of varying prognosis in patients of different primary sites of HNSCC
Detailed Description:
Potentially resectable Stage III or IV squamous cell carcinomas of the head and neck HNSCC are treated by operation and adjuvant radiotherapy The 5-year survival rate is approximating 30 Recurrence typically occurs within 3 years 60-80 in locoregional sites and 20-30 systemically Patients who are found to have tumors at the margins of surgical specimens far particularly poorly
Chemotherapy has been added in the hope to improve this situation Induction and adjuvant chemotherapy has resulted in a decrease in the appearance of systemic metastases in most trials but has not improved locoregional control and survival
For cases with unresectable head and neck cancers concurrent chemoradiotherapy appears to have improved locoregional control disease-free survival and possibly overall survival as compared to radiotherapy alone Bachaud et al reported a randomized trial of postoperative cisplatin and radiotherapy vs radiotherapy alone for patients with Stage III or IV head and neck cancer Cisplatin was administered 50 mg weekly during radiotherapy There was a significant improvement in locoregional control 70 vs 55 as well as overall survival median 36m vs 20m in patients who received concurrent chemoradiotherapy Al-Sarraf et al also reported a phase II concurrent chemoradiotherapy trial using cisplatin 100 mgm2 every three weeks Based on comparison with similar patients treated in a prior RTOG trial they conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates10 The superiority of adjuvant concurrent chemoradiotherapy CCRT to RT alone or sequential adjuvant RT and chemotherapy has been further confirmed in an analysis of data of RTOG 85-03 and RTOG 88-24 Comparing high-risk patients of RTOG 85-03 with prognostically similar patients from RTOG 88-24 the data suggest that sequential surgery RT and chemotherapy produced better locoregional control than surgery plus RT but that surgery followed by CCRT produced even higher locoregional control Independent of the differences in the amount of RT delivered the Cox proportional hazards model suggests that the addition of CCRT resulted in a 50 decrease in locoregional relapse rates compared with surgery plus postoperative RT with no chemotherapy The reduction in mortality was 18
Although CCRT may be better than RT alone or sequential treatment the 3 year survival in both adjuvant CCRT studies were only around 50 Is more aggressive treatment warranted Tolerance to CCRT is a major concern In the French study severe acute toxicity occurred in 18 of RT only patients and 41 of patients received CCRT In the RTOG 88-24 trial severe and life-threatening toxicities occurred in 20 and 12 of patients respectively the most common drug-related toxicities were leukopenia anemia nausea and vomiting Theoretically to optimize CCRT continuous presence of chemotherapeutic drug or drug effect is necessary to maximize the effect of radiosensitization For radiosensitization purpose daily chemotherapy may be better than weekly and weekly may be better than tri-weekly French study used weekly cisplatin with a dose of 30 mgm2 RTOG 88-24 used different treatment dose and schedule 100 mgm2 of cisplatin on radiotherapy days 1 23 and 43 We choose weekly for convenience and hope this can increase the recruitment of patients In the pilot study we observed a remarkable toxicity with this treatment schedule Considering the remarkable toxicity reported and our preliminary experience more drugs higher dosage or extended schedule may not be justified
Chemotherapy has been added in the hope to improve this situation Induction and adjuvant chemotherapy has resulted in a decrease in the appearance of systemic metastases in most trials but has not improved locoregional control and survival
For cases with unresectable head and neck cancers concurrent chemoradiotherapy appears to have improved locoregional control disease-free survival and possibly overall survival as compared to radiotherapy alone Bachaud et al reported a randomized trial of postoperative cisplatin and radiotherapy vs radiotherapy alone for patients with Stage III or IV head and neck cancer Cisplatin was administered 50 mg weekly during radiotherapy There was a significant improvement in locoregional control 70 vs 55 as well as overall survival median 36m vs 20m in patients who received concurrent chemoradiotherapy Al-Sarraf et al also reported a phase II concurrent chemoradiotherapy trial using cisplatin 100 mgm2 every three weeks Based on comparison with similar patients treated in a prior RTOG trial they conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates10 The superiority of adjuvant concurrent chemoradiotherapy CCRT to RT alone or sequential adjuvant RT and chemotherapy has been further confirmed in an analysis of data of RTOG 85-03 and RTOG 88-24 Comparing high-risk patients of RTOG 85-03 with prognostically similar patients from RTOG 88-24 the data suggest that sequential surgery RT and chemotherapy produced better locoregional control than surgery plus RT but that surgery followed by CCRT produced even higher locoregional control Independent of the differences in the amount of RT delivered the Cox proportional hazards model suggests that the addition of CCRT resulted in a 50 decrease in locoregional relapse rates compared with surgery plus postoperative RT with no chemotherapy The reduction in mortality was 18
Although CCRT may be better than RT alone or sequential treatment the 3 year survival in both adjuvant CCRT studies were only around 50 Is more aggressive treatment warranted Tolerance to CCRT is a major concern In the French study severe acute toxicity occurred in 18 of RT only patients and 41 of patients received CCRT In the RTOG 88-24 trial severe and life-threatening toxicities occurred in 20 and 12 of patients respectively the most common drug-related toxicities were leukopenia anemia nausea and vomiting Theoretically to optimize CCRT continuous presence of chemotherapeutic drug or drug effect is necessary to maximize the effect of radiosensitization For radiosensitization purpose daily chemotherapy may be better than weekly and weekly may be better than tri-weekly French study used weekly cisplatin with a dose of 30 mgm2 RTOG 88-24 used different treatment dose and schedule 100 mgm2 of cisplatin on radiotherapy days 1 23 and 43 We choose weekly for convenience and hope this can increase the recruitment of patients In the pilot study we observed a remarkable toxicity with this treatment schedule Considering the remarkable toxicity reported and our preliminary experience more drugs higher dosage or extended schedule may not be justified
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None