Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.

Thirty-seven men with symptomatic bone metastases from prostate cancer that had progressed following earlier treatment with estrogens and/or orchidectomy were treated with low-dose prednisone (7.5 to 10 mg daily). The rationale for this treatment was that some patients might still have hormone-sensitive disease that was stimulated by weak androgens of adrenal origin, and that these androgens could be suppressed by prednisone through its negative feedback on secretion of adrenocorticotrophic hormone (ACTH). Response to treatment was assessed by requirement for analgesics, by the McGill-Melzack pain questionnaire, and by a series of 17 linear analog self-assessment (LASA) scales relating to pain and to various aspects of quality of life. Fourteen patients (38%) had improvement in indices used to assess pain at 1 month after starting prednisone, and seven patients (19%) maintained this improvement for 3 to 30 months (median, 4 months). Reduction in pain was associated with improvement in other dimensions of quality of life, and in the scale for overall well-being. Prednisone treatment led to a decrease in the concentration of serum testosterone in seven of nine patients where it was not initially suppressed below 2 nmol/L, and caused a decrease in serum levels of androstenedione and dehydroepiandrosterone sulfate in more than 50% of patients. Symptomatic response was associated with a decrease in serum concentration of adrenal androgens. We conclude that (1) low-dose prednisone may cause useful relief of pain in some patients with advanced prostatic cancer; (2) relief of pain was associated with suppression of adrenal androgens; and (3) measures of pain and quality of life can be used to assess possible benefits of systemic therapy in patients with metastatic prostate cancer.

Summary Solid tumours develop an acidic extracellular environment with high concentration of lactic acid, and lactic acid produced by glycolysis has been assumed to be the major cause of tumour acidity. Experiments using lactate dehydrogenase (LDH)-deficient rastransfected Chinese hamster ovarian cells have been undertaken to address directly the hypothesis that lactic acid production is responsible for tumour acidification. The variant cells produce negligible quantities of lactic acid and consume minimal amounts of glucose compared with parental cells. Lactate-producing parental cells acidified lightly-buffered medium but variant cells did not. Tumours derived from parental and variant cells implanted into nude mice were found to have mean values of extracellular pH (pHe) of 7.03 ± 0.03 and 7.03 ± 0.05, respectively, both of which were significantly lower than that of normal muscle (pHe = 7.43 ± 0.03; P < 0.001). Lactic acid concentration in variant tumours (450 ± 90 ,ug g-1 wet weight) was much lower than that in parental tumours (1880 ± 140 gg/g-1) and similar to that in serum (400 ± 35 ,ug/g-1).These data show discordance between mean levels of pHe and lactate content in tumours; the results support those of Newell et al (1993) and suggest that the production of lactic acid via glycolysis causes acidification of culture medium, but is not the only mechanism, and is probably not the major mechanism responsible for the development of an acidic environment within solid tumours.

5005 Background: The TAX-327 study compared 3 weekly docetaxel (D3), weekly docetaxel (D1) or mitoxantrone (M), each with prednisone (P) for 1006 patients (pts) with metastatic hormone resistant prostate cancer (mHRPC). The original analysis, undertaken in August 2003 when 557 deaths had occurred, showed significantly better survival and response rates for pain, PSA and quality of life for D3 when compared with M (Tannock et al, NEJM 2004;351:1502–12). Here we present the updated survival analysis. Methods: Investigators were asked to provide date of death or last follow up for all patients alive in August 2003. Results: By December 2007 data on 276 additional deaths were obtained (total 833 deaths, see Table ). The survival benefit of D3 as compared with M has persisted with extended follow up while D1 continues to show no significant survival advantage. More patients (17.9% and 16.7%) survived =3 years in the D3 and D1 arms compared to M (13.7%). Similar trends in survival between treatment arms were seen for pts above and below 65 years of age, for those with and without pain at baseline, and for those with baseline PSA above and below median value of 115ng/ml. Conclusions: The present analysis confirms previous findings that survival is significantly longer with D3 than with M. Survival update is ongoing. [Table: see text] No significant financial relationships to disclose.