Reduced-dose Radiotherapy for Low-risk Stage III Patients With Nasopharyngeal Carcinoma
- Conditions
- Nasopharyngeal Carcinoma
- Interventions
- Radiation: Intensity-modulated radiation therapy
- Registration Number
- NCT03668730
- Lead Sponsor
- Sun Yat-sen University
- Brief Summary
To study the 2-year PFS (progression-free survival) of patients with stage III nasopharyngeal carcinoma of pretreatment EBV DNA\<4000 copy/ml treated with induction chemotherapy followed by two different doses of intensity-modulated radiation therapy and cisplatin.
- Detailed Description
To explore the 2 year PFS of patients with stage III nasopharyngeal carcinoma of pretreatment EBV DNA\<4000 copy/ml treated with induction chemotherapy followed by reduced-dose radiation and cisplatin. The enrolled patients will receive 2 cycles of TPF regimen induction chemotherapy, if radiographic CR/PR and EBV DNA=0 after induction chemotherapy, the patients will be delivered by 60 Gy IMRT combined with 3 cycles of cisplatin concurrent chemotherapy. If radiographic SD/PD or EBV DNA\>0 after induction chemotherapy, the patients will receive a total of 70 Gy IMRT combined with 3 cycles of cisplatin concurrent chemotherapy.
The included patients will be treated with 2 cycles of TPF regimen induction chemotherapy and 60Gy IMRT combined with cisplatin concurrent chemotherapy. The TPF regimen is consist of paclitaxel liposome 135mg/m2 d1, cisplatin 25mg/m2d1-d3 and 5-Fu 3750mg/m2 civ120h, with a total of two cycles. Concurrent cisplatin chemotherapy is delivered with dose of 100mg/m2, a total of three cycles. The third cycle of cisplatin concurrent chemotherapy is allowed to be delivered within one week after IMRT finished.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 215
- Pathological diagnosis of NPC(WHO II or III).
- Stage III（8thAJCC/UICC staging system) and pretreatment EBVDNA<4000opies/ml.
- Aged 18-70 years。
- ECOG = 0-1。
- HGB≥90 g/L，WBC≥4×109 /L，PLT≥100×109 /L.
- ALT,AST<2.5 fold of ULN；TBIL<2.0×ULN。
- CCR≥60ml/min or Cr<1.5×ULN。
- Signed informed consent
- WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
- Age <18 or >70years.
- Treatment with palliative intent.
- Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
- Pregnancy or lactation.
- History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume).
- Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
- Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose >1.5×ULN), and emotional disturbance.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Reduced dose group Intensity-modulated radiation therapy After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles. Reduced dose group Paclitaxel liposome After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles. Standard dose group Intensity-modulated radiation therapy After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles. Standard dose group Paclitaxel liposome After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles. Standard dose group 5-Fluorouracil After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles. Reduced dose group Cisplatin After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles. Reduced dose group 5-Fluorouracil After 2 cycles of induction chemotherapy with Paclitaxel Liposome, Cisplatin and 5-Fluorouracil, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive cisplatin once per three week for 3 cycles. Standard dose group Cisplatin After 2 cycles of induction chemotherapy with Paclitaxel Liposome,Cisplatin and 5-Fluorouracil, patients undergo standard-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cisplatin once per three week for 3 cycles.
- Primary Outcome Measures
Name Time Method PFS(progression free survival) 2 years Defined from date of registration to date of first documentation of progression and/or distant metastasis,or death due to any cause. The primary study population for this endpoint is patients who were confirmed post-induction CR /PR and EBV DNA=0 and subsequently received 60Gy radiation therapy.
- Secondary Outcome Measures
Name Time Method Overall response rate 2 years Tumour response rate was classified according to RECIST, version 1.1
Incidence of acute toxicity 2 years Numbers of patients of treatment-related adverse events as assessed by CTCAE v4.0.
Overall Survival(OS) 2 years Defined from date of registration to date of first documentation of death from any cause or censored at the date of the last follow-up.
Locoregional relapse-free survival(LRFS) 2 years Defined from date of registration to date of first documentation of locoregional relapse or until the date of the last follow-up visit.
Incidence of late toxicity 2 years Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.
Change of ADC( apparent diffusion coefficient ) value of DWI(Diffusion-Weighted MRI) of patients predictive of failure 2 years The ADC value of each patient of Diffusion-Weighted MRI at pretreatment and after induction chemotherapy was calculated were evaluated independently on a work station.
Change of QoL 1 years QoL scores were assessed for each scale by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy.
Change of EORTC quality of life questionnaire(QLQ) Head and Neck score 1 years QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H\&N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva, coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.
Plasma EBV DNA copy number 2 years Plasma EBV DNA copy number with either reduced or standard dose radiotherapy was assessed by qRT-PCR at pretreatment. The predictive value of plasma EBV DNA copy number was assessed by survival analysis.
Distant metastasis-free survival(DMFS) 2 years Defined from date of registration to date of first documentation of distant metastases or until the date of the last follow-up visit.
Trial Locations
- Locations (1)
Hai Qiang Mai
🇨🇳Guangzhou, Guangdong, China