Radiotherapy
while administering both hyperbaric oxygen and misonidazole was associated with
improved survival at 1 year in patients with locally advanced squamous cell
carcinoma.
Clinical Bottom Line:
1.
A combination of hyperbaric oxygen and misonidazole during irradiation of
locally advanced SCC was associated with improved survival at 1 year.
2.
The incidence of toxic effects was higher in the hyperbaric /misonidazole
group.
Appraised
by: Mike Bennett, Dept of Diving and
Hyperbaric Medicine, Prince of Wales Hospital, Sydney; Friday, 22 January, 1999
Clinical
Scenario: A patient with locally advanced
SCC of the mouth presented for radiotherapy.
Three-part
Question: In radiotherapeutic treatment of
locally advanced squamous cell carcinoma, does the addition of hyperbaric
oxygenation and misonidazole, compared to conventional air treatment, result in
any improvement in tumour control or mortality?
Search
Terms: Hyperbaric oxygenation,
misonidazole, radiotherapy.
The
Study:
Non-blinded randomised
controlled trial with intention-to-treat.
Patients with primary
presentation of locally advanced squamous cell carcinoma of the mouth or fixed
neck nodes.
Control group (N = 68; 66
analysed): Tumour dose of 63 Gy by external beam in 30 fractions over 38 days.
Experimental group (N = 68; 64
analysed): Tumour dose of 36 Gy by external beam in six fractions over 17 days
while breathing oxygen at 3ATA. Also given 2g/m2 misonidazole orally at time of
each fraction.
The
Evidence:
|
Outcome |
Time
to Outcome |
Air
rate |
Hyperbaric/
Misonidazole rate |
Relative
risk reduction |
Absolute
risk reduction |
NNT |
|
Mortality |
1
year |
0.73 |
0.531 |
27% |
0.196 |
5 |
|
95%
CI: |
|
|
|
5%
to 49% |
0.03
to 0.36 |
3
to 30 |
|
Mortality |
2
years |
0.87 |
0.75 |
13% |
0.114 |
9 |
|
95%
CI: |
|
|
|
-2%
to 29% |
-0.02
to 0.25 |
NNT=4
to INF NNH=49
to INF |
|
Toxic
events |
38
days |
0.11 |
0.469 |
-342% |
-0.363 |
-3 |
|
95%
CI: |
|
|
|
-100%
to -207% |
-0.51
to -0.22 |
-5
to -2 |
Comments:
1. Different irradiation regimes
may be important in considering the incidence of toxic effects.
2. Six patients were withdrawn
after randomisation and not analysed, low follow-up rates at 2 yrs.
4. Some suggestion of greater
benefit in tumours of greater mass.
5. Relative contribution of two
agents remains unknown.
Expiry
date:
January 2004
References:
1. Sealy R, Cridland S, Barry L,
Norris R. Irradiation with misonidazole and hyperbaric oxygen: final report on a
randomised trial in advanced head and neck cancer. International Journal of
Radiation Oncology and Biological Physics 1986; 12:1343-1346.
2. Sealy R. A preliminary clinical study in the use of misonidazole in cancer of the head and neck. British Journal of Cancer 1978; 37 (Suppl III):314-317.
