title: A phase I/II study of high-dose tamoxifen in combination with vinblastine in patients with androgen-independent prostate cancer.
abstract: In this phase I/II clinical trial the antitumor activity of high-dose tamoxifen when administered in combination with vinblastine was assessed and the toxicity profile of this combination characterized. All 25 patients enrolled in this study were required to have androgen-independent prostate cancer and to maintain androgen ablation during treatment. Vinblastine was given by continuous infusion over 5 days. Doses were increased from 0.9 mg/m2/day to 1.5 mg/m2/day in successive cohorts of at least 3 patients, with no further escalation even in the absence of dose-limiting toxicity. Intra-patient dose escalation was permitted. Tamoxifen was administered at a dose of 200 mg/kg on day 1, then 120 mg/kg/day on day 2. Standard response criteria were utilized to assess antitumor activity and CTC toxicity criteria were used. Quality of life (QOL) pain assessments were evaluated at each visit to the clinic. Most patients tolerated the highest dose of vinblastine at 1.5 mg/m2/day by continuous infusion over 5 days with 200 mg/kg/day of tamoxifen on day 1 and day 2. One patient had a greater than 50% decline in prostate-specific antigen that lasted for 170 days. Two patients received dose reductions because of toxicity. The most common serious toxicities included neutropenia, and fatigue. Reversible neurosensory, neuromotor, neurocortical and neurocerebellar toxicities were reported. Six of the 25 patients enrolled in the study (24%) experienced reversible neurologic toxicity of at least grade III. No statistically significant differences between precycle assessment of QOL and subsequent cycles were observed. It is concluded that vinblastine at 1.5 mg/m2/day continuous i.v. infusion combined with tamoxifen 200 mg/kg/day on day 1 and day 2 is inactive, and not without toxicity in the treatment of advanced metastatic androgen-independent prostate cancer.
authors.affiliation: Medicine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hamilton
authors.forename: William
authors.initials: W
authors.lastname: Dahut
authors.forename: Otis
authors.initials: O
authors.lastname: Brawley
authors.forename: Patricia
authors.initials: P
authors.lastname: Davis
authors.forename: Toni
authors.initials: T
authors.lastname: Wells-Jones
authors.forename: David
authors.initials: D
authors.lastname: Kohler
authors.forename: Paul
authors.initials: P
authors.lastname: Duray
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: Nehal
authors.initials: N
authors.lastname: Lakhani
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Eddie
authors.initials: E
authors.lastname: Reed
mesh_terms: D000368:Aged; D000728:Androgens / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010146:Pain; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000728:Androgens; D013629:Tamoxifen; D014747:Vinblastine