Mitomycin C Versus Estramustine in the Treatment of Hormone Resistant Metastatic Prostate Cancer: Thefinal Analysis of the European Organization Forresearch and Treatment of Cancer, Genitourinarygroup Prospective Randomized Phase III Study (30865)

Abstract

A total of 171 patients with progressive metastatic prostate cancer following hormonal therapy was randomized to receive either 560 to 700 mg. estramustine orally per day or 15 mg./m.2 mitomycin C by intravenous infusion every 6 weeks. The patients were recruited during a 2.5-year period, and 70% had undergone more than 1 previous therapy for prostate cancer, with some having received as many as 5 different previous treatments. The overall results were disappointing. The median time to progression was 5 months and 50% of the patients died within 10 months. There was no difference in efficacy between the 2 treatment arms. Toxicity was severe in both arms but appeared earlier in those patients receiving estramustine, leading to a tendency for earlier deterioration in performance status. In this group of heavily pretreated patients there appears to be no justification for the use of either of these agents at the present time.

Quality of Life of Patients with Newly Diagnosed Poor Prognosis M1 Prostate Cancer Undergoing Orchiectomy without or with Mitomycin C

“…As many as 43% of all patients were ≥70 years of age. A few years after initiation of trial 30893 two other reports described a relatively high level of toxicity in prostate cancer patients receiving MMC: Newling et al [21]reported nausea in 44% and vomiting in 32% of the patients with hormone–resistant prostate cancer receiving MMC, and in the report of Van Poppel et al [22], 17% of the patients had to discontinue treatment due to toxicity.…”

Chemotherapy in Hormone Refractory Prostate Cancer

“…In six randomized NPCP trials, only 6 of 217 HRPC patients (2.8%) achieved an objective response to single-agent estramustine [10,[25][26][27][28][29]. No improvement in mean survival time was seen over patients who received no chemotherapy [10,25,30]. In addition, estramustine was not found to be superior to other single-agent regimens such as cisplatin, methotrexate, mitomycin C or vincristine.…”

“…There is also in vitro and in vivo evidence that estramustine binds to the nuclear matrix and possibly induces cell death via disturbances in macromolecular synthesis [22]. Estramustine has been extensively tested in HRPC patients, and as a single agent its benefits are minimal [10,[23][24][25][26][27][28][29][30][31][32]. The comparison of these studies, mainly from the pre-PSA era, is difficult due to the use of variable tumour response including the controversial category of stable disease as well as variable patient selection criteria [5].…”

Epirubicin combined with estramustine phosphate in hormone-resistant prostate cancer: a phase II study

“…Dependent on selection criteria of the patients and the definition of response criteria, EMP has shown variable response rates (Benson et al, 1986). In the clinical situation it has been difficult to prove the cytotoxic effect of single-drug EMP therapy (Newling et al, 1993;Fossa et al, 1990), whereas the British Joumal of Cancer (1997) 76(1), [93][94][95][96][97][98][99] results of recent trials combining EMP with etoposide and vinblastine are more promising (Hudes et al, 1992;Seidnian et al, 1992;Pienta et al, 1994). The concomitant use of EPR precludes any statement about EMP-induced bone marrow suppression in our trial.…”

“…No consensus exists on the optimum medical treatment of this condition, which conventionally comprises progressive disease in spite of castration levels of serum testosterone. The median survival of symptomatic patients with hormone-resistant prostate cancer (HRPC) is 8-10 months (Foss'a et al, 1992a;Newling et al, 1993). Androgen independence most probably reflects the selection of hormoneresistant cell clones.…”