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(188)Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study.

Lam MG, Bosma TB, van Rijk PP, Zonnenberg BA - Eur. J. Nucl. Med. Mol. Imaging (2009)

Bottom Line: Secondary end-points included the effect of capecitabine on the biodistribution and pharmacokinetics of (188)Re-HEDP.Capecitabine had no effect on uptake or excretion of (188)Re-HEDP.Capecitabine may be safely used in combination with (188)Re-HEDP in a dose of 2,500 mg/m(2) per day and 37 MBq/kg, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. M.Lam@umcutrecht.nl

ABSTRACT

Purpose: (188)Re-HEDP is indicated for the treatment of pain in patients with painful osteoblastic bone metastases, including hormone-refractory prostate cancer patients. Efficacy may be improved by adding chemotherapy to the treatment regimen as a radiation sensitizer. The combination of (188)Re-HEDP and capecitabine (Xeloda(R)) was tested in a clinical phase I study.

Methods: Patients with hormone-refractory prostate cancer were treated with capecitabine for 14 days (oral twice daily in a dose escalation regimen with steps of 1/3 of 2,500 mg/m(2) per day in cohorts of three to six patients, depending on toxicity). Two days later patients were treated with 37 MBq/kg (188)Re-HEDP as an intravenous injection. Six hours after treatment post-therapy scintigraphy was performed. Urine was collected for 8 h post-injection. Follow-up was at least 8 weeks. The primary end-point was to establish the maximum tolerable dose (MTD) of capecitabine when combined with (188)Re-HEDP. Secondary end-points included the effect of capecitabine on the biodistribution and pharmacokinetics of (188)Re-HEDP.

Results: Three patients were treated in the first and second cohorts, each without unacceptable toxicity. One of six patients in the highest cohort experienced unacceptable toxicity (grade 4 thrombopaenia). The MTD proved to be the maximum dose of 2,500 mg/m(2) per day capecitabine. No unexpected toxicity occurred. Capecitabine had no effect on uptake or excretion of (188)Re-HEDP.

Conclusion: Capecitabine may be safely used in combination with (188)Re-HEDP in a dose of 2,500 mg/m(2) per day and 37 MBq/kg, respectively. Efficacy will be further studied in a phase II study using these dosages.

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Related in: MedlinePlus

Mean haematological parameters (±1 standard deviation) during the study period of 9 weeks: haemoglobin in mmol/l (a), platelet count × 109/l (b) and white blood cell count × 109/l (c)
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Fig1: Mean haematological parameters (±1 standard deviation) during the study period of 9 weeks: haemoglobin in mmol/l (a), platelet count × 109/l (b) and white blood cell count × 109/l (c)

Mentions: After onset of the study treatment, haematological parameters were measured on a weekly basis (Fig. 1) and serum chemistry on a monthly basis (Table 2). All patients experienced an expected temporary decline in platelet count in week 4 (mean ± 1 SD: −61.8 ± 16.5%), 3 weeks after 188Re-HEDP administration, with subsequent recovery (Fig. 1). Also as expected, there was a temporary decline in white blood cell count in week 4 (mean ± 1 SD: −34.4 ± 17.8%), 3 weeks after 188Re-HEDP administration, with recovery thereafter. The temporary increase in mean white blood cell count in week 5 may be due to inter- and intra-patient variations, typically seen in white blood cell count. It was probably not related to the study treatment. Haemoglobin levels were steady throughout the study course with a mean change compared to baseline of −0.8 ± 12.7% 4 weeks after 188Re-HEDP administration and −5.8 ± 11% at the end of the study (Fig. 1).Fig. 1


(188)Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study.

Lam MG, Bosma TB, van Rijk PP, Zonnenberg BA - Eur. J. Nucl. Med. Mol. Imaging (2009)

Mean haematological parameters (±1 standard deviation) during the study period of 9 weeks: haemoglobin in mmol/l (a), platelet count × 109/l (b) and white blood cell count × 109/l (c)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2724641&req=5

Fig1: Mean haematological parameters (±1 standard deviation) during the study period of 9 weeks: haemoglobin in mmol/l (a), platelet count × 109/l (b) and white blood cell count × 109/l (c)
Mentions: After onset of the study treatment, haematological parameters were measured on a weekly basis (Fig. 1) and serum chemistry on a monthly basis (Table 2). All patients experienced an expected temporary decline in platelet count in week 4 (mean ± 1 SD: −61.8 ± 16.5%), 3 weeks after 188Re-HEDP administration, with subsequent recovery (Fig. 1). Also as expected, there was a temporary decline in white blood cell count in week 4 (mean ± 1 SD: −34.4 ± 17.8%), 3 weeks after 188Re-HEDP administration, with recovery thereafter. The temporary increase in mean white blood cell count in week 5 may be due to inter- and intra-patient variations, typically seen in white blood cell count. It was probably not related to the study treatment. Haemoglobin levels were steady throughout the study course with a mean change compared to baseline of −0.8 ± 12.7% 4 weeks after 188Re-HEDP administration and −5.8 ± 11% at the end of the study (Fig. 1).Fig. 1

Bottom Line: Secondary end-points included the effect of capecitabine on the biodistribution and pharmacokinetics of (188)Re-HEDP.Capecitabine had no effect on uptake or excretion of (188)Re-HEDP.Capecitabine may be safely used in combination with (188)Re-HEDP in a dose of 2,500 mg/m(2) per day and 37 MBq/kg, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. M.Lam@umcutrecht.nl

ABSTRACT

Purpose: (188)Re-HEDP is indicated for the treatment of pain in patients with painful osteoblastic bone metastases, including hormone-refractory prostate cancer patients. Efficacy may be improved by adding chemotherapy to the treatment regimen as a radiation sensitizer. The combination of (188)Re-HEDP and capecitabine (Xeloda(R)) was tested in a clinical phase I study.

Methods: Patients with hormone-refractory prostate cancer were treated with capecitabine for 14 days (oral twice daily in a dose escalation regimen with steps of 1/3 of 2,500 mg/m(2) per day in cohorts of three to six patients, depending on toxicity). Two days later patients were treated with 37 MBq/kg (188)Re-HEDP as an intravenous injection. Six hours after treatment post-therapy scintigraphy was performed. Urine was collected for 8 h post-injection. Follow-up was at least 8 weeks. The primary end-point was to establish the maximum tolerable dose (MTD) of capecitabine when combined with (188)Re-HEDP. Secondary end-points included the effect of capecitabine on the biodistribution and pharmacokinetics of (188)Re-HEDP.

Results: Three patients were treated in the first and second cohorts, each without unacceptable toxicity. One of six patients in the highest cohort experienced unacceptable toxicity (grade 4 thrombopaenia). The MTD proved to be the maximum dose of 2,500 mg/m(2) per day capecitabine. No unexpected toxicity occurred. Capecitabine had no effect on uptake or excretion of (188)Re-HEDP.

Conclusion: Capecitabine may be safely used in combination with (188)Re-HEDP in a dose of 2,500 mg/m(2) per day and 37 MBq/kg, respectively. Efficacy will be further studied in a phase II study using these dosages.

Show MeSH
Related in: MedlinePlus