title: Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer: a phase I clinical trial.
abstract: OBJECTIVE
  This is a phase I study investigating the toxicity and the potential efficacy of thalidomide and oral cyclophosphamide in patients with hormone refractory prostate cancer (HRPC), previously treated with docetaxel-based regimens.
  
  
  METHODS
  Two dose levels of thalidomide (100 and 200 mg every day) were studied. Patients were accrued to each dose level in cohorts of 3 starting from dose 1 level (100 mg). Thalidomide was started on day 1 at the assigned dose and continued for four consecutive weeks; oral cyclophosphamide (50 mg for day) was given for four consecutive weeks (1 cycle) starting on the same day initiating thalidomide. Toxicity was evaluated every two weeks; changes in prostate-specific antigen (PSA) levels were evaluated every cycle. Treatment was planned for four cycles.
  
  
  RESULTS
  Sixteen men were treated. Ten patients in cohort 1, and 6 in cohort 2 were enrolled respectively. Grade 1-2 constipation, peripheral neuropathy and fatigue were the most common side effects, noted in 6 (37.5%), 5 (31.25%) and 3 (19%) patients, respectively. Three patients stopped the treatment at level 2, during the first cycle, for toxicity. Those three patients were evaluable only for toxicity. The MTD was 100 mg thalidomide. Thirteen patients completed two cycles. Two patients (15%) had a >50% decrease in PSA, while in one patient (8%) the PSA decrease was less of 50%. Overall PSA decrease was of 23%.
  
  
  CONCLUSIONS
  The oral combination of thalidomide and cyclophosphamide is well tolerated and appears to be associated with biochemical response in this population. Future phase II trials, in pre-treated and untreated patients, are needed to evaluate clinical efficacy of this regimen in HRPC.
authors.affiliation: Cattedra di Oncologia Medica, Dipartimento di Endocrinologia e Oncologia molecolare e clinica, Università degli Studi di Napoli Federico II, Napoli, Italy. giuseppedilorenzoncol@hotmail.com
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Autorino
authors.forename: Michele
authors.initials: M
authors.lastname: De Laurentiis
authors.forename: Valeria
authors.initials: V
authors.lastname: Forestieri
authors.forename: Carmela
authors.initials: C
authors.lastname: Romano
authors.forename: Antonella
authors.initials: A
authors.lastname: Prudente
authors.forename: Francesco
authors.initials: F
authors.lastname: Giugliano
authors.forename: Ciro
authors.initials: C
authors.lastname: Imbimbo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mirone
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000728:Androgens / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000627:therapeutic use; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D043823:Taxoids; D000077143:Docetaxel; D013792:Thalidomide; D003520:Cyclophosphamide; D017430:Prostate-Specific Antigen