Randomized trial of oral adjuvant razoxane (ICRF 159) in resectable colorectal cancer: Five-year follow-up

Abstract

Razoxane is one of the few agents which has shown activity in the treatment of advanced colorectal cancer. The drug has therefore been evaluated in a prospective randomized controlled trial as an adjuvant to surgery for resectable colorectal cancer. The results to median follow-up of 5 years are reported here. Accrual has ceased and a total of 272 patients entered the trial (133 control, 139 treatment). Treated patients received razoxane postoperatively on a continuous, long-term basis while control patients received identical clinical care but no adjuvant chemotherapy. Analysis of the results shows a significant prolongation of the time to recurrence for Dukes' C patients. All other groups including the overall analysis show no benefit although there is a consistent trend in favour of the treated patients except in Dukes' group 'D'. Razoxane is tolerated well by patients and causes minimal side-effects. However acute leukaemia occurred in three patients (2.45 per cent) after prolonged exposure to the drug and further evaluation should be in patients who are at high risk of developing recurrent cancer, in whom such a risk may be acceptable. It is concluded that razoxane is suitable for further evaluation in colorectal cancer and for incorporation into combination chemotherapy regimens.

The prognostic impact of the time interval to recurrence for the mortality in recurrent colorectal cancer

“…The relationship between the recurrence interval and the use of adjuvant therapy remained controversial [23,24,26,27]. Intuitively, one would expect adjuvant therapy to suppress the recurrence and prolong the time until a recurrence would be clinically evident.…”

Effect of razoxane on metastases from colorectal cancer

“…The overall results in terms of survival or recurrence of the adjuvant razoxane trial in resectable CRC have been published [2]. In summary the trial produced no evidence of any benefit for patients in Dukes' groups A, B or D, but there was clear evidence of delay in recurrence of Dukes' group C patients (P= 0"05).…”

“…It should be emphasized however that, theoretically at least, while antimetastatic drugs might hinder or prevent development of distant metastasis they might not necessarily prevent or even hinder continued growth of local tumour that remained unresected or distant metastasis already present at the start of treatment with the antimetastatic drug. The overall effect of razoxane on these two parameters has been published [2], but the present report deals more specifically with the development of metastases in the trial patients and the role of razoxane as an antimetastatic drug. Razoxane slows down or prevents the development of metastases, but without influencing the growth rate of the primary tumours in 8/10 spontaneously metastasizing experimental tumours (table 1).…”

Multimodale Therapie des Coloncarcinoms

“…Eine randomisierte Studie konnte bei 272 Patienten eine Verbesserung des 5-Jahres-Überlebens bei langjähriger oraler Einnahme von Razoxane beobachten [16]. Razoxane hemmt den Zellzyklus prämitotisch vor der G2/M-Phase und kann oral verabreicht werden.…”