title: Assessment of bone response to systemic therapy in an EORTC trial: preliminary experience with the use of collagen cross-link excretion. European Organization for Research and Treatment of Cancer.
abstract: This study was designed to evaluate new bone resorption and tumour markers as possible alternatives to serial plain radiographs for the assessment of response to treatment. Thirty-seven patients with newly diagnosed bone metastases from breast cancer, randomized to receive oral pamidronate or placebo tablets in addition to anticancer treatment within the context of a multicentre EORTC trial, who were both assessable for radiographic response in bone and had serum and urine samples collected for more than 1 month were studied. The markers of bone metabolism measured included urinary calcium (uCa), hydroxyproline (hyp), the N-telopeptide cross-links of type I collagen (NTx) and total alkaline phosphatase. The tumour markers measured were CA15-3 and cancer-associated serum antigen (CASA). Before treatment, levels of Ntx, uCa and Hyp were elevated in 41%, 24% and 28% respectively, and CA15-3 and CASA increased in 69% and 50%. For assessment of response and identification of progression, Ntx was the most useful bone marker. All markers behaved similarly in no change (NC) and partial response (PR) patients. There was a significant difference (P < or = 0.05) in Ntx levels (compared to baseline) at 1 and 4 months and in CA15-3/CASA at 4 months between patients with PR or NC and those with progressive disease (PD), and at 4 months between those with time to progression (TP) > 7 and those with TP < or = 7 months. The diagnostic efficiency (DE) for prediction of PD following a > 50% increase in Ntx or CA15-3 was 78% and 62% respectively. An algorithm to predict response to therapy has been developed for future prospective evaluation.
authors.affiliation: EORTC, Breast Cancer Cooperative Group, Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vinholes
authors.forename: R
authors.initials: R
authors.lastname: Coleman
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: C
authors.initials: C
authors.lastname: Rose
authors.forename: M
authors.initials: M
authors.lastname: Tubiana-Hulin
authors.forename: P
authors.initials: P
authors.lastname: Bastit
authors.forename: J
authors.initials: J
authors.lastname: Wildiers
authors.forename: J
authors.initials: J
authors.lastname: Michel
authors.forename: R
authors.initials: R
authors.lastname: Leonard
authors.forename: J
authors.initials: J
authors.lastname: Nortier
authors.forename: F
authors.initials: F
authors.lastname: Mignolet
authors.forename: J
authors.initials: J
authors.lastname: Ford
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D001862:Bone Resorption; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D000077268:Pamidronate; D010455:Peptides / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D024042:Collagen Type I; D004164:Diphosphonates; D018396:Mucin-1; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000077268:Pamidronate