Purpose: AK-2123, a nitrotriazole hypoxic cell sensitizer, has reportedly improved results in head and neck cancers, uterine cervical cancers and other solid tumours when added to radical radiotherapy. A prospectively randomised trial was initiated by the International Atomic Energy Agency (IAEA) evaluating AK-2123 and radiotherapy in treatment of uterine cervical cancer stage III and IV.
Patients and methods: A total of 462 patients were randomised from 8 centres. Patients from four centres were excluded due to lack of accrual, closing of the centre and insufficient documentation and reporting. The final study population consisted of 333 patients who were randomised between May 1995 and December 1998. Patients were randomised to either standard radical treatment (radiation therapy alone, RT) or standard radical radiotherapy and additional administration of AK-2123 (RT+AK-2123). The total dose of 45-50.8 Gy was delivered by 20-28 fractions in an overall time of 4-5 1/2 weeks, with further dose escalation by brachytherapy or external beam. In the study arm, patients received 0.6 g/sqm AK-2123 by intravenous administration before external beam radiotherapy, treating with AK-2123 on alternate days (e.g. Monday-Wednesday-Friday) during the entire course of external beam therapy. Following exclusion of 7 patients who did not undergo treatment, a total of 326 patients remained for evaluation.
Results: The rate of local tumour control was significantly higher in the group after radiotherapy and additional administration of AK-2123. Local tumour control was 61% (95/155) after AK-2123 and 46% (79/171) after radiotherapy alone (p=0.006). The actuarial survival at 60 months was 57% after RT+AK-2123, compared to 41% after RT (Log Rank p=0.01). AK-2123 did neither increase gastro-intestinal toxicity nor was it attributed to any haematological toxicity. A mild peripheral toxicity (Grade 1: 13% and Grade 2: 2%) usually completely reversible was infrequently seen after AK-2123 administration.
Conclusion: We conclude that the addition of AK-2123 to radical radiotherapy significantly increases local tumour control and survival in advanced squamous cell cancer of the uterine cervix without the addition of any major toxicity.