Assessment of bone response to systemic therapy in an EORTC trial: preliminary experience with the use of collagen cross-link excretion

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 meta stases from breast cancer, randomized to receive oral pamidronate or placeb o tablets in addition to anticancer treatment within the context of a multi centre EORTC trial, who were both assessable for radiographic response in b one and had serum and urine samples collected for more than 1 month were st udied. The markers of bone metabolism measured included urinary calcium (uC a), 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 identifi cation of progression, Ntx was the most useful bone marker. All markers beh aved similarly in no change (NC) and partial response (PR) patients. There was a significant difference (P less than or equal to 0.05) in Ntx levels ( compared to baseline) at 1 and 4 months and in CA15-3/CASA at 4 months betw een 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 less than or equal to 7 months. The diagnostic efficiency (DE) for predicti on of PD following a > 50% increase in Ntx or CA15-3 was 78% and 62% respec tively. An algorithm to predict response to therapy has been developed for future prospective evaluation.