Thalidomide in Combination with Oral Daily Cyclophosphamide in Patients with Pretreated Hormone Refractory Prostate Cancer: A Phase I Clinical Trial

Giuseppe Di Lorenzo, Riccardo Autorino, Michele De Laurentiis, Valeria Forestieri, Carmela Romano, Antonella Prudente, Francesco Giugliano, Ciro Imbimbo, Vincenzo Mirone and Sabino De Placido

volume 6 | issue 3

March 2007
Pages: 313 - 317

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Aim. 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 4 consecutive weeks; oral cyclophosphamide (50 mg for day) was given for 4 consecutive weeks (1 cycle) starting on the same day initiating thalidomide. Toxicity was evaluated every 2 weeks; changes in prostate-specific antigen (PSA) levels were evaluated every cycle. Treatment was planned for 4 cycles.

Results. 16 men were treated. 10 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 7 (44%), 6 (37.5%) and 3 (19%) patients, respectively. 3 patients stopped the treatment at level 2, during the first cycle, for toxicity. Those 3 patients were evaluable only for toxicity. The MTD was 100 mg thalidomide. 13 patients completed 2 cycles. 2 patients (15%) had a > 50% decrease in PSA, while in 1 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.