Cisplatin increases the hearing loss produced by radiotherapy

This Singapore study shows that the addition of cisplatin to conventional high dose radiotherapy in the treatment of nasopharyngeal cancer increases the risk of high tone hearing loss.Sensorineural hearing loss is an important adverse effect of irradiation. It may be of early or late onset and the extent of hearing loss is related to the radiotherapy dose. It mostly affects the higher frequencies and can have important effects on speech recognition. There is little data on the synergistic ototoxicity of radiation and cisplatin.The study population was drawn from a randomised trial of chemoradiotherapy in nasopharyngeal cancer. Patients were treated to a dose of 70 Gy in 35 fractions, which gave a mean dose to the inner ear of 47 Gy. Cisplatin was given for four days, three times during radiotherapy, and with 5-fluorouracil for four days for three cycles after radiotherapy.One hundred and fifteen patients from the Singapore General Hospital had bone conduction hearing thresholds performed before treatment and at one week, six months, one and two years after completion of radiotherapy. High frequencies in the speech range were represented by the threshold at 4 kHz and lower frequencies by the average of 0.5, 1, and 2 kHz.In the lower speech frequencies, hearing levels were significantly worse in the 58 patients in the chemoradiotherapy group than in the 57 patients in the radiotherapy alone group one and two years after radiotherapy, but not at one week and six months after radiotherapy. The median hearing levels were still at the upper end of normal.Hearing thresholds at higher frequencies, at 4 kHz, were significantly worse in the chemoradiotherapy group at all times and were much more severely affected than the lower speech frequencies; the median threshold at two years was 25 dB in the radiotherapy and 55 dB in the chemoradiation group. In the radiotherapy group, deterioration of median hearing thresholds started immediately, improved by one year and deteriorated again at two years. In the chemoradiotherapy group, the deterioration started immediately after radiotherapy but stabilised by one year.The authors concluded that those patients who were treated with concurrent or adjuvant cisplatin had greater hearing loss than those treated with radiotherapy alone. The standard normal inner ear tissue tolerance doses (5 and 50% probability of complication within five years from treatment of the inner ear of 60 and 70 Gy respectively) were originally defined for radiotherapy alone, but the authors concluded that these should now be redefined for chemoradiotherapy.Reference...