Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Apr;80(1-2):221–228. doi: 10.1038/sj.bjc.6690506

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

J Vinholes 1, R Coleman 1, D Lacombe 2, C Rose 1, M Tubiana-Hulin 1, P Bastit 1, J Wildiers 1, J Michel 1, R Leonard 1, J Nortier 1, F Mignolet 2, J Ford 3
PMCID: PMC2362989  PMID: 10390000

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 ≤ 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 ≤ 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. © 1999 Cancer Research Campaign

Keywords: bone metastases, assessment of response, breast cancer, bone resorption markers, tumour markers

Full Text

The Full Text of this article is available as a PDF (108.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blomqvist C., Risteli L., Risteli J., Virkkunen P., Sarna S., Elomaa I. Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma. Br J Cancer. 1996 May;73(9):1074–1079. doi: 10.1038/bjc.1996.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blumsohn A., Herrington K., Hannon R. A., Shao P., Eyre D. R., Eastell R. The effect of calcium supplementation on the circadian rhythm of bone resorption. J Clin Endocrinol Metab. 1994 Sep;79(3):730–735. doi: 10.1210/jcem.79.3.8077353. [DOI] [PubMed] [Google Scholar]
  3. Bonde M., Qvist P., Fledelius C., Riis B. J., Christiansen C. Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment. J Clin Endocrinol Metab. 1995 Mar;80(3):864–868. doi: 10.1210/jcem.80.3.7883844. [DOI] [PubMed] [Google Scholar]
  4. Campbell F. C., Blamey R. W., Woolfson A. M., Elston C. W., Hosking D. J. Calcium excretion (CaE) in metastatic breast cancer. Br J Surg. 1983 Apr;70(4):202–204. doi: 10.1002/bjs.1800700405. [DOI] [PubMed] [Google Scholar]
  5. Coleman R. E. Monitoring of bone metastases. Eur J Cancer. 1998 Feb;34(2):252–259. doi: 10.1016/s0959-8049(97)10134-4. [DOI] [PubMed] [Google Scholar]
  6. Coleman R. E., Rubens R. D. Bone metastases and breast cancer. Cancer Treat Rev. 1985 Dec;12(4):251–270. doi: 10.1016/0305-7372(85)90008-8. [DOI] [PubMed] [Google Scholar]
  7. Coleman R. E., Whitaker K. B., Moss D. W., Mashiter G., Fogelman I., Rubens R. D. Biochemical prediction of response of bone metastases to treatment. Br J Cancer. 1988 Aug;58(2):205–210. doi: 10.1038/bjc.1988.194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hanson D. A., Weis M. A., Bollen A. M., Maslan S. L., Singer F. R., Eyre D. R. A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine. J Bone Miner Res. 1992 Nov;7(11):1251–1258. doi: 10.1002/jbmr.5650071119. [DOI] [PubMed] [Google Scholar]
  9. Howell A., Mackintosh J., Jones M., Redford J., Wagstaff J., Sellwood R. A. The definition of the 'no change' category in patients treated with endocrine therapy and chemotherapy for advanced carcinoma of the breast. Eur J Cancer Clin Oncol. 1988 Oct;24(10):1567–1572. doi: 10.1016/0277-5379(88)90046-6. [DOI] [PubMed] [Google Scholar]
  10. Robertson J. F., Pearson D., Price M. R., Selby C., Blamey R. W., Howell A. Objective measurement of therapeutic response in breast cancer using tumour markers. Br J Cancer. 1991 Oct;64(4):757–763. doi: 10.1038/bjc.1991.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Vinholes J. J., Purohit O. P., Abbey M. E., Eastell R., Coleman R. E. Relationships between biochemical and symptomatic response in a double-blind randomised trial of pamidronate for metastatic bone disease. Ann Oncol. 1997 Dec;8(12):1243–1250. doi: 10.1023/a:1008238422151. [DOI] [PubMed] [Google Scholar]
  12. Vinholes J., Guo C. Y., Purohit O. P., Eastell R., Coleman R. E. Evaluation of new bone resorption markers in a randomized comparison of pamidronate or clodronate for hypercalcemia of malignancy. J Clin Oncol. 1997 Jan;15(1):131–138. doi: 10.1200/JCO.1997.15.1.131. [DOI] [PubMed] [Google Scholar]
  13. Vinholes J., Guo C. Y., Purohit O. P., Eastell R., Coleman R. E. Metabolic effects of pamidronate in patients with metastatic bone disease. Br J Cancer. 1996 May;73(9):1089–1095. doi: 10.1038/bjc.1996.210. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES