Serum Osteocalcin Concentration in Patients with Prostatic Cancer

Summary This randomised phase II study was performed in order to evaluate the effectiveness of a weekly chemotherapy regimen in advanced prostatic carcinoma patients (stage D2) refractory to hormonal therapy. Seventy-two cases were studied: they were randomised in a 2:1 ratio to receive either epirubicin (30 mgm 2 weekly) or doxorubicin (25 mg m weekly); 48 patients received epirubicin and 24 received doxorubicin.After 12 courses of chemotherapy, the 45 evaluable patients in the epirubicin arm showed a response rate of 37.7% and the 21 evaluable patients in the doxorubicin arm showed a response rate of 33.3% (P = 0.51) Pain intensity, bone and prostatic tumour markers rapidly and significantly decreased in responders. An improvement in physical symptoms, functional conditions and in emotional well-being was observed in the majority of the treated patients.The histological analysis of bone metastases, performed before and after 12 courses of chemotherapy showed a significant reduction in neoplastic invasion and in new bone formation in responders.Cardiac performance worsened in five out of 45 patients and in ten out of 21 during the first 12 courses of epirubicin or doxorubicin respectively (P = 0.014).The median survival was 12.5 months in the epirubicin arm and 8.0 months in the doxorubicin arm (P = 0.042).Our data indicate that in advanced prostatic carcinoma, a weekly epirubicin regimen may give rapid palliative results, similar to that of doxorubicin, but with less side-effects.

Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Weekly chemotherapy in advanced prostatic cancer

Francini

Petrioli²,

Manganelli³

et al. 1993

“…In NC, FLARE, CR and IMP, bone formation and resorption were essentially balanced even though bone formation was slightly greater than bone resorption. (Francini et al, 1988;Shin et al, 1990;Arai et al, 1992;Sano et al, 1994;Koizumi et al, 1995). The phenotypic developmental sequence of osteoblasts has been divided into three consecutive phases: proliferation, extracellular matrix maturation and mineralization (Stein et al, 1990; Risteli and Risteli, 1993;Zhou et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

Dissociation of bone formation markers in bone metastasis of prostate cancer

Koizumi

Maéda²,

Yoshimura³

et al. 1997

Summary To clarify the meaning and clinical value of bone formation markers in bone metastasis from prostate cancer, we investigated the bone formation markers carboxy-terminal propeptide of type procollagen (PICP), bone-specific alkaline phosphatase (BAl-p) and osteocalcin, so-called bone gla protein (BGP) in 43 prostate cancer patients with and 46 patients without overt bone metastasis. Patients with bone metastasis were evaluated repeatedly by bone scan at intervals of 3-6 months. The expression patterns of bone formation markers in patients with progression of bone metastasis became dissociated; BAl -p and PICP were elevated in patients with progression of bone metastasis but BGP was not. Instead, BGP showed slight elevation in patients with improvement and complete remission of bone metastasis. PICP, BAl-p and BGP are all bone formation markers, but each marker appears in a different phase of bone formation: PICP appears in proliferation phase, BAl -p appears in matrix maturation phase and BGP appears in late bone formation phase. Our findings that BGP was not elevated in progression of bone metastasis and that it increased slightly with improvement and complete remission of bone metastasis may imply that the bone formation that occurs in blastic bone metastasis is different from normal bone formation.Keywords: prostate cancer; bone metastasis; carboxy-terminal propeptide of type procollagen; bone-specific alkaline phosphatase; bone gla protein Bone metastasis from prostate cancer is frequently osteoblastic in nature, and it often shows up as osteoplastic changes on plain radiography. Recently, various bone metabolic markers of both formation and resorption have been identified. Bone resorption markers have been proven to be useful in the bone metastasis of prostate cancer (Kylmala et al, 1995; Maeda et al, 1996). However, the meaning of bone formation markers is not fully understood in bone metastasis of prostate cancer. Various bone formation markers have been found to be associated with certain phases of bone formation. The carboxy-terminal propeptide of type I procollagen (PICP) is believed to be a marker of early bone formation and it generally appears during osteoblast proliferation. Bone-specific alkaline phosphatase (BAl-p) is a marker of the middle stage of bone formation and it appears in the matrix maturation phase. Osteocalcin, so-called bone gla protein (BGP), is a marker of late bone formation and it appears in the mineralization phase (Stein et al, 1990;Risteli and Risteli, 1993;Zhou et al, 1994;Calvo et al, 1996). To clarify the meaning of bone formation markers, we investigated these three markers in prostate cancer patients with and without overt bone metastasis. PATIENTS AND METHODSBetween October 1994 and April 1996, 43 prostate cancer patients with and 46 patients without overt bone metastasis were studied with respect to bone formation markers. Of the 46 patients without Institute Hospital, 1-37-1 Kami-lkebukuro, Toshima-ku, Tokyo 170, Japan overt bone metastasis, 29 had a history of r...

“…The number of bone metastases was evaluated by bone scan and the nature of the sclerotic or lytic component by radiography. Skeletal metastases can also be investigated with biochemical markers (Francini et al, 1988;Mulders et al, 1989Mulders et al, , 1992 (Charhon et al, 1985;Urwin et al, 1985). Another possibility is that the osteolysis may be due to circulating tumour-generated factors such as epidermal growth factor (EGF), transforming growth factor alpha (TGF-a) and platelet-derived growth factor (PDGF), which could promote osteoclast overactivity (Mundy, 1988;Vaes, 1988;Morris and Dodd, 1990 …”

Section: Survivalmentioning

confidence: 99%

Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer

Kylmälä

Tammela²,

Risteli³

et al. 1995

(Klein, 1979; Elder and Catalona, 1984). Bone metastases occur in approximately 85% of patients who die of the disease (McCrea et al., 1958;Jacobs et al., 1983). Although bone-forming metast are charactenrstic of prostate cancer, bone resorption is also accelerated, as evidenced by an increase in the urinary hydroxyproline excretion and by the presence of lytic bone lesions in radiographs (Hopkins et al., 1983;Urwin et al., 1985;Percival et al., 1987;Shimazaki et al., 1990). Also, histomorphometnrc examination of skeletal biopsies has confirmed an enhanced osteolysis (Charhon et al., 1983;Urwin et al., 1985; Clarke et al., 1992;Taube et al., 1994). The main symptom of bone metastases is pain, but lytic lesions may sometimes also lead to pathological fractures and hypercalcaemia. Although most patients with bony metastases respond to the first-line hormonal therapy, the median survival is between 2 and 3 years, and only 30% are alive after 5 years (Murphy et al., 1983).The major structural protein in bone is type I collagen, which is synthesised by osteoblasts and accounts for about 90% of the organic matrix of bone (Risteli et al., 1993 (1988). The types of metastases were evaluated by radiographs, which showed sclerotic metastases without a visible lytic component (S) in 23 patients (58%) and mixed metastases with sclerotic and lytic components (S + L) in 17 patients (42%). Intermittent or constant bone pain had led to