CONCURRENT CHEMORADIATION IN LOCALLY ADVANCED HEAD AND NECK CANCER --CAPECITABINE & CISPLATIN Vs CISPLATIN- A RANDOMISED PROSPECTIVE COMPARATIVE STUDY
Koustav Mazumder *, Shyamal K Sarkar
*Department of Radiotherapy & Oncology, PGIMER, Chandigarh, India
Department of Radiotherapy, Medical College & Hospital , Kolkata, India
CAPECITABINE CISPLATIN CHEMORADIATION
BACKGROUND: Aim of my study is to compare the response and toxicity profile of squamous cell carcinoma of Head & Neck(SCHNC) patients when in concurrent chemoradiation( CTRT) Capectabine is combined with cisplatin vs cisplatin alone.
METHODS: 55 patients of stage III/IV nonmetastatic SCHNC patients were either treated with CTRT with Cisplatin & Capecitabine arm(Arm A, n=29), or with Cisplatin (Arm B, n=26). In both the arm Radiotherapy dose was 66 - 70 Gy in conventional fractionation. Response was assessed by RECIST criteria after 6 wks of completion of treatment and acute toxicities by the RTOG/EORTC guideline. Comparison was done by Chi-Square test, Fisher’s Exact test & Independent T test using SPSS Software.
RESULTS: It was seen that 65.5% patient in Arm A & 34.6% patients in Arm B [p=.022] showed complete response. The grade 2/3 acute toxicities of Skin, Mucous Membrane ,Salivary gland in Arm A & B were 72.4% & 30.8% [p=.005]; 69%&15.4% [p<.001]; 58.6% & 11.5% [p<.001] respectively. Significant acute grade 2/3 toxicities of Esopagus+pharynx [p<.001],Larynx[p=.001] &Upper GI tract[p=.001] were also present in the patients of ArmA.
COLCLUSIONS: In locally advanced nonmetastatic SCHNC during CTRT combining Capecitabine with Cisplatin results in significant response benefit but toxicities are more.
Head Neck carcinoma is one of the prevalent cancers in the Indian scenario. And among all of it Squamous cell carcinoma is mostly occurred. More than fifty thousand head and neck squamous cell carcinomas (HNSCC) are diagnosed worldwide each year, . Among oral cavity and oropharynx, the most common site of involvement is the tongue (32.7%). Male are more affected than females with a ratio of 3:1 . Combined modalities of treatment viz. Surgery, Radiation therapy, Chemotherapy became the standard of care head & neck cancer. But for the organ preservation concurrent chemoradiotherapy(CCRT) is used in a large extent in locally advanced cases. Only radiation therapy can give maximum of 50-70 % of local control rate . So chemotherapy is used concurrently for more local control rate and increasing the survival benefit.
Cisplatin based CCRT became the standard management in locally advanced head & neck squamous cell carcinoma (LAHNSCC) region. The treatment is well tolerated by the patients and having local control increased by 15 – 25% and survival rate more than that of Radiation therapy alone.
5 Flurouracil is also a common agent used in CCRT in head neck cancer from few decades. Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil in the tumor. Capecitabine is an orally-administered chemotherapeutic drug used mainly in the treatment of metastatic breast and colorectal cancers.
While administrating inj 5FU along with cisplatin concurrently with radiation the patient have to get admitted for 4 days. And the concurrent effect of the drugs only present in for those few days. So if we administer capecitabine continuously in place of 5FU then the concurrent effect would remain more than that of the continuous infusion of 5FU.
The aim of my study is to evaluate and compare the local control rate and toxicity profile of locally advanced head & neck squamous cell cancer when in concurrent chemoradiation Capectabine is combined with cisplatin vs cisplatin alone.
Materials and methods
Total 129 patients with head & neck cancer came in our department for management were selected. The inclusion criteria for this study was a)Age more than 20 years up to 65 years b) Histologically confirmed primary squamous cell carcinoma of Head and Neck c) Patient should have stage III or non- metastatic stage IV d) Ecog performance status should have £ 2 e) all patient medically suitable for concurrent chemoradiotherapy f) no history of cancer g) routine blood report e.g. Complete haemogram , LFT(Liver function test), RFT(Renal Function test) were within normal limit h) having proper written consent from the patients.
According to the inclusion criteria among all 129 patients 94 patients were selected for 1:1 randomization. Ultimately 29 patients of Chemoradiation with Cisplatin with Capecitabine ( ARM A) and 26 patients of Chemoradiation with cisplatin(ARM B) only were finally analysed and this selection process is shown in Fig 1.
In Arm A in CCRT, chemotherapy was given with Injection Cisplatin 60mg/m2 I.V 3 weekly with Oral Capecitabine 900mg/m2 BD Day 1 – Day 14 , 3 weekly . In Arm B in CCRT, the chemotherapy part was given with Injection Cisplatin 100mg/m2 I.V, 3 weekly. As tab Capecitabine had given along with Inj cisplatin in the study arm the dose of Inj Cisplatin was reduced(60mg/m2).
In both the arm EBRT dose was 66 – 70 Gy with 2 Gy/fraction, 5 days in a week with single fraction per day. EBRT was given with Theratron 780C (Cobalt60 megavoltage machine).
Pre treatment assessment includes: (a) Detailed history of present illness. (b) Clinical along with ENT examination (c )Biopsy from the primary site (d) Contrast enhanced CT scan of Head and Neck (e) Routine investigations – Complete Haemogram, Biochemistry (urea/creatinine/LFT) (f) Dental evaluation (g) Chest X ray to exclude distal metastasis (Lung is the commonest site).
Evaluation after completion of therapy includes (a) Clinical Examination with ENT examination area (b) Complete Haemogram, Biochemistry (urea/creatinine/LFT) (c) CECT of Head neck region (d) Biopsy from the suspicious clinical and /or radiological residual disease of primary or nodal area.
During treatment weekly toxicity assessment was done using clinical status, laboratory tests and graded according to RTOG/EORTC Acute and chronic Radiation morbidity scheme. Acute toxicity assessment was continued for an additional 8 Weeks from the last date of radiation. And in this study the late toxicity after 3 months of the completion of treatment was taken and analysed. The response assessment was done according to the RECIST criteria and categorised into Complete Response ( CR) , Partial Response (PR),Stable Disease (SD) , Progressive Disease (PD). 
Patients were followed-up thereafter at 1- 3 monthly intervals till the end of study with clinical examination and contrast enhanced CT scan of head and neck done 6-monthly or before in patients with suspicion for recurrence. Recurrence was proven by biopsy.
STATISTIC :Statistical analysis was done using SPSS version 20. For categorical variables, Chi Square and Fisher Exact tests were used, while for continuous variables, the mean and SD were compared using Independent samples t test with 95% CI. All tests were 2-tailed and P less than 0.05 were taken as significant. The Recurrence free survival (RFS) was determined using the Kaplan Meier survival analysis with Log Rank test for comparing the RFS.
Assessed for eligibility (n= 129) )
Excluded (n= 35 )
Not meeting inclusion criteria (n= 23 )
Declined to participate (n= 12 )
Other reasons (n= 0 )
Analysed (n= 29 )
Excluded from analysis (n= 0 )
Lost to follow-up (n= 9 )
Discontinued intervention (Death) (n= 3)
Allocated to intervention (n= 42 )
Received allocated intervention (n=41 )
Did not receive allocated intervention (Socioeconomic condition) (n= 1 )
Lost to follow-up (n= 13 )
Discontinued intervention (Death) (n=1 )
Analysed (n= 26 )
Excluded from analysis (n= 0 )