Trial Information

Phase III Trial of Surgery Followed by Conventional RT(5fr/Week)Vs.Concurrent Chemo-Radiotherapy Vs.Accelerated RT(6fr/Week)in High Risk, Loco-Regionally Advanced, Stage III&IVA, Resectable, Squamous Cell Carcinomas of Oralcavity

Locally advanced, stage III and IVA, resectable, squamous cell carcinomas of oral cavity are
conventionally treated with surgery, followed by post-operative radiotherapy. Local-regional
recurrence remains the most frequent cause of failure of this treatment. The results of
conventional therapy are dismal with five-year survival of less than 30% and 60-80%
incidence of local-regional failure within 3 years. There are various known histological
prognostic factors. The local-regional control and overall survival are extremely poor in
high risk patients with these poor prognostic factors. In an attempt to improve the outcome
of this high risk group, various alternative treatment policies such as addition of
chemotherapy to radiotherapy or altered fractionation schedules have been tried. But till
date, there is no alternative treatment modality with acceptable toxicity, available for
these patients.

Aims Of Study: To demonstrate whether addition of Concurrent chemotherapy to post-operative
adjuvant radiotherapy OR shortening of duration of post-operative radiotherapy, by
administering 6 fractions / week instead of 5 fractions / week improves local-regional
control and / or overall survival in high risk, locally advanced, resectable, squamous cell
carcinoma of oral cavity.

Eligibility criteria: Locally advanced, stage III and IVA, resectable, squamous cell
carcinomas of oral cavity with one of the following poor prognostic factors extracapsular
nodal extension, involvement of > 2 regional lymph nodes, margin of resection with invasive
cancer Extensive soft tissue and / or skin infiltration requiring major reconstructive
procedure.

Peri-neural invasion with positive lymph node. Lympho-vascular embolisation with positive
lymph node.

Trial Design The eligible patients will be randomly allocated to one of the three arms

1. Arm 1 (Control arm): Surgery followed by conventional radiotherapy

2. Arm 2: Surgery followed by Concurrent chemo-radiotherapy

3. Arm 3: Surgery followed by Accelerated radiotherapy

Surgery: Surgery will be same in all three arms. Wide excision tumour with appropriate nodal
dissection and reconstruction utilizing accepted criteria for the region involved will be
done.

Radiotherapy: Total dose of radiotherapy will be 56 – 60 Gy. Patients in Arms 1 and 2, five
fractions per week for six weeks. Patients in Arm 3, six fractions a week for five weeks.

Chemotherapy: Patients in Arm 2 will get weekly chemotherapy (Inj Cisplatin 30 mg / m2)

Stratification: Patients will be stratified according to following factors Site:
Gingivo-buccal complex cancers Vs Tongue and Floor of mouth cancers. T stage. N stage.
Extra-capsular spread (Peri-nodal extension) Surgical margin Extensive soft tissue
infiltration

End points Primary end point: Local-regional failure. Secondary end point: Overall survival.
Other parameters to be assessed are Treatment related toxicity Protocol compliance Overall
treatment time Quality of life: assessment by EORTC-QLQ-C30 and EORTC-H&N-35 Sample size:
900 pts (300 pts in each arm). Duration of accrual: 7 years. Duration of follow up: 5 years.
With minimum follow up of 2 years. Analysis: Intent to treat analysis will be done. Interim
analysis will be done after 450 patients (150 pts in each arm)