vitamin-d-2 and Neoplasm-Metastasis

Docetaxel is standard of care for androgen-independent prostate cancer (AIPC). Doxercalciferol (1 alpha-hydroxyvitamin D2) had modest activity in phase I/II trials. Preclinical data support combining vitamin D analogues with docetaxel to treat AIPC.. Chemotherapy-naive men with metastatic AIPC were randomized 1:1 to receive, on a 4-week cycle, docetaxel (35 mg/m2 i.v., days 1, 8, and 15) with or without doxercalciferol (10 microg orally, days 1-28). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were progression-free survival, overall survival, objective response, and toxicity. Survival was analyzed as intent to treat.. Seventy patients were randomized. Median follow-up was 17.6 months (range, 3.3-45.2). PSA response rate was 46.7% [95% confidence interval (95% CI), 30-64] in the doxercalciferol arm and 39.4% (95% CI, 25-56) with placebo (P = 0.560). Median progression-free survival in the doxercalciferol arm was 6.17 months (95% CI, 4.20-10.7) versus 6.20 months (95% CI, 4.83-9.07) with placebo (P = 0.764). Median overall survival in the doxercalciferol arm was 17.8 months (95% CI, 14.9-23.6) versus 16.4 months (95% CI, 11.9-23.8) with placebo (P = 0.383). Twenty-four patients in the doxercalciferol arm and 23 in the placebo arm were evaluable for objective response. No complete responses were observed. Partial objective response rate was 12.5% with doxercalciferol versus 8.7% with placebo (P = 0.672). Rate of grade > or =3 toxicity was 46% with doxercalciferol versus 42% with placebo (P = 0.785).. Daily doxercalciferol with weekly docetaxel did not enhance PSA response rate or survival. Toxicity was similar between arms. Despite the disappointing results of this study, other vitamin D analogues remain under active investigation.

Topics: Aged; Aged, 80 and over; Androgens; Antineoplastic Combined Chemotherapy Protocols; Calcium; Docetaxel; Double-Blind Method; Ergocalciferols; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Taxoids

In this single institution Phase II trial, we evaluated the efficacy of the vitamin D analogue, 1alpha-OH-D(2), in patients with advanced hormone-refractory prostate cancer.. The patients initially received 1alpha-OH-D(2) at 12.5 micro g p.o. every day, which was dose adjusted for hypercalcemia. Given the cytostatic nature of the drug, the primary study end point was progression-free survival for a minimum of 6 months. The secondary end point was further characterization of drug toxicity.. A total of 26 patients was enrolled. Using the intent-to-treat population, stable disease was seen for an average of 19.2 weeks (median 12 weeks, range 3-108 weeks). Twenty patients were evaluable for response. The one patient that achieved disease stabilization for >2 years elected to come off-study because of patient preference. His last disease evaluation showed no evidence of progression. No objective responses were seen. Previous and ongoing clinical observations strongly imply that PSA could be a misleading surrogate marker for clinical effect with this type of drug. Therefore, prostate-specific antigen was not used as a marker for disease response. Toxicity was as expected with mild hypercalcemia and associated symptoms like constipation and prerenal azotemia seen in some patients. Six (30%) evaluable patients experienced stable disease for >6 months, suggesting possible cytostatic activity.. The results of this and other trials suggest further clinical investigation in this disease with vitamin D analogues alone or in combination with other agents, such as chemotherapy, should be pursued.

Topics: Administration, Oral; Aged; Aged, 80 and over; Androgens; Ergocalciferols; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Osteocalcin; Palliative Care; Prostatic Neoplasms; Survival Analysis; Time Factors; Treatment Outcome

A case of hypophosphataemic osteomalacia occurring in association with a carcinoma of prostate is described. Although only palliative treatment to the primary tumour was possible, worthwhile remission of bone symptoms, due to osteomalacia, was achieved with pharmacological doses of vitamin D. The presence of extensive skeletal metastases modified the radiological features of osteomalacia. Major alterations in the distribution of calcium within the skeleton were observed during a period when total body calcium remained unaltered. This observation may be of relevance to other cases in which osteosclerotic metastases develop.

Topics: Acid Phosphatase; Aged; Body Weight; Bone and Bones; Bone Neoplasms; Calcium; Carcinoma; Ergocalciferols; Humans; Male; Neoplasm Metastasis; Osteomalacia; Prostatic Neoplasms; Radiography; Vitamin D

Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Calcinosis; Calcitonin; Cholecalciferol; Cyclophosphamide; Ergocalciferols; Fractures, Spontaneous; Humans; Hypercalcemia; Kidney Calculi; Lung Neoplasms; Male; Neoplasm Metastasis; Osteitis Deformans; Plicamycin; Podophyllin; Quinones; Sarcoma; Vitamin D

Topics: Adolescent; Bone Neoplasms; Calcinosis; Calcium; Calcium Isotopes; Ergocalciferols; Feces; Geriatrics; Humans; Hyperparathyroidism; Hypoparathyroidism; Inositol; Intestinal Absorption; Malabsorption Syndromes; Neoplasm Metastasis; Neoplasms; Osteitis Deformans; Osteomalacia; Pancreatitis; Sarcoidosis; Tetany; Urine