Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers.

PURPOSE: Based on in vitro and on clinical evidence of protection against acute side effects of radiation, a prospective randomized, open study was performed to determine the efficacy of an oral proteolytic enzyme preparation in patients with head and neck cancer receiving conventional fractionated radiation therapy. METHODS: Patients with stage T3/T4 head and neck cancer were eligible. One hundred patients from two centres were entered into the study. 60Co gamma-radiation was delivered at a standard daily radiation dose of 2 Gy in 25-35 fractions over a period of 6-7 weeks. Two lateral parallel opposing fields were used with a portal area of 10 x 15 cm. Patients assigned to the test group arm additionally received enzyme tablets orally t.i.d. starting 3 days prior to radiation therapy, and continuing up to 5 days after completion of the course of radiation therapy. Patients in the control arm were not given any drug or placebo. Acute radiation side effects were described as mucositis, skin reaction, dysphagia, and were graded at each visit during and after radiation therapy, following RTOG/EORTC criteria. RESULTS: The severity (maximum extent) of acute radiation therapy side effects was significantly less in enzyme-treated patients than in control patients: mucositis (mean: 1.3 vs 2.2, P < 0.001), skin reaction (1.2 vs 2.4, P < 0.001) and dysphagia (1.4 vs 2.2, P < 0.001). The duration of these side effects as well as the sum scores of side effects were also less in the study arm. CONCLUSIONS: Combination of enzyme therapy with conventional fractionated radiation therapy was feasible and well-tolerated. There was significant protection against acute side effects of radiation therapy in the study arm. Not only was the severity of acute side effects less but the duration was shorter and the time to onset was also delayed. Prospective randomized double-blind studies would verify this role of an oral enzyme therapy as standard co-medication with radiation therapy to the head and neck region.

The role of Wobe-Mugos in reducing acute sequele of radiation in head and neck cancers--a clinical phase-III randomized trial.

Oral enzymes act as a potent antiinflammatory, antiedematous agents thereby decreasing acute toxigenic effect of radiation and increasing compliance, quality of life of our patients. Fifty patients were randomized 25 allocated in enzyme and radiotherapy arm, 25 in radiotherapy alone. Pre RT and post RT biopsies were taken from both arms. In our study it was found that there was clinical, histopathological as well as statistical significant difference in both arms. The enzyme arm patients had mucostis of grade I in 76%, grade II in 12%, grade III in 8% while as 8% had grade I, 68% grade II, 24% had grade III in RT arm alone. In enzyme patients skin reactions of grade I in 72%, 20% had grade II, 8% had grade III. In control arm 12% had grade I, 76% had grade II, 8% had grade III skin reaction.

Hyperfractionation in advanced head and neck cancer.

This preliminary study was undertaken to observe tumour response and normal tissue tolerance to hyperfractionation. This study showed encouraging locoregional control rate in advanced head and neck cancer. Responses T4 tumors are poor and are prone to recur. This indicates that probably greater dose is needed to control T4 disease. We used 7920 cGy for T4 and late T3 status tumour. This dose is well tolerated by patients. Control of T4 tumours may further be increased by increasing total dose, but in view of inadequate clear cut numerical data of tissue tolerance derived by L-Q = Linear Quadratic formula which is still under clinical trial, further increase in total dose cannot be overemphasized. Longer follow up is necessary to assess the long term control rate and late tissue reaction. There is a need of randomized controlled clinical trial to compare hyperfractionation and conventional fractionation. In next phase we are undertaking randomized study of twice daily, daily and weekly fractionation in advanced head and neck cancer.