KETOCONAZOLE FOR PROSTATE CANCER

696

Ciprofloxacin penetrated prostatic tissue well and rapidly (figure). On average, tissue levels exceeded serum concentrations threefold; individual ratios between prostate and serum levels ranged from 125 to 648% (mean±SD 296±180%). In agreement with previous data4serum concentrations fell from the second hour after injection onwards with a half-life of 4-4h. These results confirm that ciprofloxacin is concentrated in the extravasal space. After oral administration ciprofloxacin was concentrated in prostatic tissue twofold and in seminal plasma tenfold as compared with the corresponding serum concentrations.5,6 In contrast, norfloxacin attains, after two oral 400 mg doses, prostatic concentrations not significantly different from serum levels.7 Ciprofloxacin levels in the prostate exceed minimal inhibitory concentrationsl,2 for a wide variety of pathogens which account for a large percentage of prostatic infections.8 Thus, ciprofloxacin may be a promising agent in the treatment of prostatic and urinary-tract infections; preliminary data indicate that ciprofloxacin is very effective in the treatment of acute as well as chronic and complicated

urinary-tract

infections.

Department of Urology, St Radboud University Hospital, 6500 HB Nijmegen, Netherlands

J. B. J. BOEREMA

Bayer Research Centre, Institute of Microbiology, Wuppertal, West Germany

F. M. J. DEBRUYNE AXEL DALHOFF

R, Andrews JM, Edwards LJ. In vitro activity of BAY o 9867, a new quinoline derivative, compared with those of other antimicrobial agents. Antimicrob Ag Chemother 1983; 23: 559-64. Zeiler H-J, Grohe K. In vitro and in vivo activity of ciprofloxacin (BAY o 9867), a new

1. Wise

2.

highly active quinoline carboxylic acid derivative. Eur J Clin Microbiol (in press). Crump B, Wise R, Dent J. Pharmacokinetics and tissue penetration of ciprofloxacin. Antimicrob Ag Chemother 1983; 24: 784-86. 4. Wingender W, Graefe KH, Gau W, Förster D, Beermann D, Schacht P. Pharmacokinetics of ciprofloxacin after oral and intravenous administration in healthy male volunteers. Eur J Clin Microbiol (in press). 5. Boerema JBJ, Dalhoff A. Ciprofloxacin distribution in prostatic tissue and fluid following oral administration Chemotherapy (in press). 6. Dalhoff A, Weidner W. Diffusion of ciprofloxacin into prostatic fluid. Eur J Clin Microbiol (in press). 7. Bologna M, Vaggi L, Forchetti CM, Martini E. Bactericidal intraprostatic concen3.

trations of norfloxacin. Lancet 1983; ii: 280. 8. Editorial. Chronic bacterial prostatitis Lancet 1983;

ii:

393-94.

and vomiting was a major problem associated with high dose ketoconazole. Six of fifteen patients were unable to tolerate 400 mg three times daily and seven patients on a 200 mg dose had persisting nausea throughout the treatment period. Hammersmith

Hospital and Royal Postgraduate Medical School,

1. Chisholm GD, Beynon LL. The response of malignant prostate to endocrine treatment In: Ghanadian R, ed. The endocrinology of prostate tumours. Lancaster: MTP, 1983: 241-62

ADJUVANT CHEMOTHERAPY IN BREAST CANCER SIR,-The trial reported by Dr Howell and colleagues (Aug 11, p 307) further weakens the case for adjuvant chemotherapy in operable breast cancer. An important finding is that chemotherapy delayed local recurrence but had no effect on the development of systemic metastases and, consequently, no effect on survival. Local recurrence is preventable by postoperative radiotherapy, which is a much more acceptable treatment than a year of cyclical combination chemotherapy. We disagree with the conclusion that a "beneficial effect" of chemotherapy has been demonstrated by this study. What was the policy for treatment of the two groups on relapse? Patients previously treated with chemotherapy might be expected to respond less frequently to cytotoxic drugs. Moreover if, as Howell et al suggest, the cytotoxic agents are operating through a hormonal mechanism, chemotherapy treated patients might, in relapse, also respond less frequently to hormone therapy. Survival after relapse might therefore be shorter in the chemotherapy group, and this might constitute a further contraindication to the routine use of postoperative adjuvant chemotherapy. Department of Radiotherapy and Oncology, University College Hospital,

SIR,-The suggestion by Dr Trachtenberg and Dr Pont (Aug 25, p 443) that ketoconazole might be useful as sole therapy for carcinoma of the prostate is not borne out by their findings. On the contrary, their data clearly show that ketoconazole is not at all suitable as sole therapy. At one month testosterone was measured in only twelve patients and was below 3 - 5 nmol/l in only seven (the castrate level being less than 2 nmol/1). The mean serum testosterone then rose steadily, reaching 5 1 nmol/at 180 days. The androgen-lowering effect of ketoconazole lasts about 8 h, after which testosterone rises under the influence of a progressively increasing luteinising hormone (LH). Very few patients will be able to maintain a strict 8-hourly dose regimen necessary to maintain a constant lowering of testosterone. This combination of inadequate testicular and gonadotropin suppression detracts from any value of the drug as sole therapy for carcinoma of the prostate. I and my colleagues have treated twenty patients with relapsed prostatic cancer with high dose ketoconazole, using 200 mg or 400 mg three times daily for up to nine months. They had all been previously castrated or had castrate levels of testosterone as a result of LH releasing hormone therapy. As a result of the ketoconazole therapy, testosterone levels have been further reduced and adrenal androgen production has been suppressed. Five objective and ten subjective responses’ have been seen in this group of patients, who had relapsed after conventional endocrine therapy. This emphasises the importance of the concept of total androgen ablation for the treatment of both new and relapsed cases of prostatic cancer, and I agree with Trachtenberg and Pont that ketoconazole may have a role as part of a combination therapy. However, persistent nausea

R. L. SOUHAMI

J. S. TOBIAS

London WCIE 6AU

EFFECTS OF &ohgr;-3 FATTY ACIDS ON SERUM LIPIDS

SIR,-In our long-term open studyl of the effect ofcu-3 fatty acids the serum lipids, bleeding time, and glyceryl-trinitrate consumption of patients with cardiovascular disease we reported a highly significant fall in mean serum-triglyceride concentration and a significant depression in the total cholesterol fraction after 2 years on

with w-3-rich fish oil. HDL cholesterol rose and significantly this suggests that supplementation of the diet with co-3 fatty acids may confer some long-term benefit by delaying the formation of atheroma and reducing the likelihood of thrombosis. We report here the results of a double-blind cross-over study of 16 male hypertriglyceridaemic subjects. After the fasting lipid baseline had been established over a 4-week period the subjects were given capsules containing either Igw-6-rich corn/olive oil mixture or Ig co-3-rich fish oil (Maxepa, 18% C20:5). The subjects were asked to take 5 capsules twice daily with food for 2 months. This was followed by a 1-month washout period before the subjects took the alternative capsule for a further 2 months. The results demonstrate that oj-3 fatty acids are more effective than oj-6 fatty acids in the modification of serum lipids (see table). This study supports the view that w-3 as well as w-6 fatty acids are essential fatty acids.2,3 The optimum dose of w-3 fatty acids for a beneficial effect on lipoproteins and haemostasis now needs to be of

KETOCONAZOLE FOR PROSTATE CANCER

GORDON WILLIAMS

London W12 0HS

treatment

SERUM LIPIDS AFTER DIETARY SUPPLEMENTATION WITH VEGETABLE OIL AND MAXEPA*

* Dose =5 capsules

twice

daily

with food ie, 10 ml oil

daily (1

8 g essential

fatty acid)