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, Sabino De Placido

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Abstract

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 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.

Original languageEnglish
Pages (from-to)313-317
Number of pages5
JournalCancer Biology and Therapy
Volume6
Issue number3
Publication statusPublished - Mar 2007

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Clinical Trials, Phase I
Thalidomide
Cyclophosphamide
Prostatic Neoplasms
Hormones
Prostate-Specific Antigen
docetaxel
Peripheral Nervous System Diseases
Constipation
Fatigue

Keywords

  • Angiogenesis inhibitors
  • Hormone refractory prostate cancer
  • Oral chemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer : A phase I clinical trial. / Di Lorenzo, Giuseppe; Autorino, Riccardo; De Laurentiis, Michele; Forestieri, Valeria; Romano, Carmela; Prudente, Antonella; Giugliano, Francesco; Imbimbo, Ciro; Mirone, Vincenzo; De Placido, Sabino.

In: Cancer Biology and Therapy, Vol. 6, No. 3, 03.2007, p. 313-317.

Research output: Contribution to journalArticle

Di Lorenzo, G, Autorino, R, De Laurentiis, M, Forestieri, V, Romano, C, Prudente, A, Giugliano, F, Imbimbo, C, Mirone, V & De Placido, S 2007, 'Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer: A phase I clinical trial', Cancer Biology and Therapy, vol. 6, no. 3, pp. 313-317.
Di Lorenzo, Giuseppe ; Autorino, Riccardo ; De Laurentiis, Michele ; Forestieri, Valeria ; Romano, Carmela ; Prudente, Antonella ; Giugliano, Francesco ; Imbimbo, Ciro ; Mirone, Vincenzo ; De Placido, Sabino. / Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer : A phase I clinical trial. In: Cancer Biology and Therapy. 2007 ; Vol. 6, No. 3. pp. 313-317.
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abstract = "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 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.",
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AU - Di Lorenzo, Giuseppe

AU - Autorino, Riccardo

AU - De Laurentiis, Michele

AU - Forestieri, Valeria

AU - Romano, Carmela

AU - Prudente, Antonella

AU - Giugliano, Francesco

AU - Imbimbo, Ciro

AU - Mirone, Vincenzo

AU - De Placido, Sabino

PY - 2007/3

Y1 - 2007/3

N2 - 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 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.

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