A randomized phase II pilot trial of adjuvant marimastat in patients with early-stage breast cancer

K. D. Miller, W. Gradishar, L. Schuchter, Joseph A. Sparano, M. Cobleigh, N. Robert, H. Rasmussen, G. W. Sledge

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background: This pilot trial was performed to evaluate the safety, toxicity and pharmacokinetics of chronic therapy with the matrix metalloproteinase inhibitor marimastat in the adjuvant treatment of breast cancer. Patients and methods: Patients with high-risk node negative or node positive breast cancer received marimastat either 5 or 10 mg p.o. b.i.d. for 12 months. Marimastat was given either as a single agent following completion of adjuvant chemotherapy or concurrently with tamoxifen. Results: Sixty-three patients were enrolled from June 1997 to May 1998. All patients have completed 12 months of treatment or have discontinued therapy due to toxicity, relapse or intercurrent illness. Moderate (WHO criteria) arthralgia/arthritis was reported by 34% of patients receiving 5 mg b.i.d. and 45% of patients receiving 10 mg b.i.d.; severe arthralgia/arthritis was reported by 6% and 23% of patients, respectively. Six patients (19%) receiving 5 mg b.i.d. and 11 (35%) receiving 10 mg b.i.d. discontinued marimastat therapy due to toxicity. Trough plasma levels were rarely within the target range for biological activity (40-200 ng/ml) with mean concentration for patients receiving: 5 mg b.i.d. = 7.5; 5 mg b.i.d. plus tamoxifen = 6.9; 10 mg b.i.d. = 11.9; 10 mg b.i.d. plus tamoxifen = 12.8. Conclusions: A randomized adjuvant trial with marimastat is not warranted as chronic administration cannot maintain plasma levels with the target range.

Original languageEnglish (US)
Pages (from-to)1220-1224
Number of pages5
JournalAnnals of Oncology
Volume13
Issue number8
DOIs
StatePublished - Aug 2002

Fingerprint

Breast Neoplasms
Tamoxifen
Arthralgia
Arthritis
Glycyrrhetinic Acid
Therapeutics
marimastat
Matrix Metalloproteinase Inhibitors
Adjuvant Chemotherapy
Pharmacokinetics
Safety
Recurrence

Keywords

  • Angiogenesis
  • Breast cancer
  • Metalloproteinase
  • Metalloproteinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Miller, K. D., Gradishar, W., Schuchter, L., Sparano, J. A., Cobleigh, M., Robert, N., ... Sledge, G. W. (2002). A randomized phase II pilot trial of adjuvant marimastat in patients with early-stage breast cancer. Annals of Oncology, 13(8), 1220-1224. https://doi.org/10.1093/annonc/mdf199

A randomized phase II pilot trial of adjuvant marimastat in patients with early-stage breast cancer. / Miller, K. D.; Gradishar, W.; Schuchter, L.; Sparano, Joseph A.; Cobleigh, M.; Robert, N.; Rasmussen, H.; Sledge, G. W.

In: Annals of Oncology, Vol. 13, No. 8, 08.2002, p. 1220-1224.

Research output: Contribution to journalArticle

Miller, KD, Gradishar, W, Schuchter, L, Sparano, JA, Cobleigh, M, Robert, N, Rasmussen, H & Sledge, GW 2002, 'A randomized phase II pilot trial of adjuvant marimastat in patients with early-stage breast cancer', Annals of Oncology, vol. 13, no. 8, pp. 1220-1224. https://doi.org/10.1093/annonc/mdf199
Miller, K. D. ; Gradishar, W. ; Schuchter, L. ; Sparano, Joseph A. ; Cobleigh, M. ; Robert, N. ; Rasmussen, H. ; Sledge, G. W. / A randomized phase II pilot trial of adjuvant marimastat in patients with early-stage breast cancer. In: Annals of Oncology. 2002 ; Vol. 13, No. 8. pp. 1220-1224.
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abstract = "Background: This pilot trial was performed to evaluate the safety, toxicity and pharmacokinetics of chronic therapy with the matrix metalloproteinase inhibitor marimastat in the adjuvant treatment of breast cancer. Patients and methods: Patients with high-risk node negative or node positive breast cancer received marimastat either 5 or 10 mg p.o. b.i.d. for 12 months. Marimastat was given either as a single agent following completion of adjuvant chemotherapy or concurrently with tamoxifen. Results: Sixty-three patients were enrolled from June 1997 to May 1998. All patients have completed 12 months of treatment or have discontinued therapy due to toxicity, relapse or intercurrent illness. Moderate (WHO criteria) arthralgia/arthritis was reported by 34{\%} of patients receiving 5 mg b.i.d. and 45{\%} of patients receiving 10 mg b.i.d.; severe arthralgia/arthritis was reported by 6{\%} and 23{\%} of patients, respectively. Six patients (19{\%}) receiving 5 mg b.i.d. and 11 (35{\%}) receiving 10 mg b.i.d. discontinued marimastat therapy due to toxicity. Trough plasma levels were rarely within the target range for biological activity (40-200 ng/ml) with mean concentration for patients receiving: 5 mg b.i.d. = 7.5; 5 mg b.i.d. plus tamoxifen = 6.9; 10 mg b.i.d. = 11.9; 10 mg b.i.d. plus tamoxifen = 12.8. Conclusions: A randomized adjuvant trial with marimastat is not warranted as chronic administration cannot maintain plasma levels with the target range.",
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AU - Cobleigh, M.

AU - Robert, N.

AU - Rasmussen, H.

AU - Sledge, G. W.

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N2 - Background: This pilot trial was performed to evaluate the safety, toxicity and pharmacokinetics of chronic therapy with the matrix metalloproteinase inhibitor marimastat in the adjuvant treatment of breast cancer. Patients and methods: Patients with high-risk node negative or node positive breast cancer received marimastat either 5 or 10 mg p.o. b.i.d. for 12 months. Marimastat was given either as a single agent following completion of adjuvant chemotherapy or concurrently with tamoxifen. Results: Sixty-three patients were enrolled from June 1997 to May 1998. All patients have completed 12 months of treatment or have discontinued therapy due to toxicity, relapse or intercurrent illness. Moderate (WHO criteria) arthralgia/arthritis was reported by 34% of patients receiving 5 mg b.i.d. and 45% of patients receiving 10 mg b.i.d.; severe arthralgia/arthritis was reported by 6% and 23% of patients, respectively. Six patients (19%) receiving 5 mg b.i.d. and 11 (35%) receiving 10 mg b.i.d. discontinued marimastat therapy due to toxicity. Trough plasma levels were rarely within the target range for biological activity (40-200 ng/ml) with mean concentration for patients receiving: 5 mg b.i.d. = 7.5; 5 mg b.i.d. plus tamoxifen = 6.9; 10 mg b.i.d. = 11.9; 10 mg b.i.d. plus tamoxifen = 12.8. Conclusions: A randomized adjuvant trial with marimastat is not warranted as chronic administration cannot maintain plasma levels with the target range.

AB - Background: This pilot trial was performed to evaluate the safety, toxicity and pharmacokinetics of chronic therapy with the matrix metalloproteinase inhibitor marimastat in the adjuvant treatment of breast cancer. Patients and methods: Patients with high-risk node negative or node positive breast cancer received marimastat either 5 or 10 mg p.o. b.i.d. for 12 months. Marimastat was given either as a single agent following completion of adjuvant chemotherapy or concurrently with tamoxifen. Results: Sixty-three patients were enrolled from June 1997 to May 1998. All patients have completed 12 months of treatment or have discontinued therapy due to toxicity, relapse or intercurrent illness. Moderate (WHO criteria) arthralgia/arthritis was reported by 34% of patients receiving 5 mg b.i.d. and 45% of patients receiving 10 mg b.i.d.; severe arthralgia/arthritis was reported by 6% and 23% of patients, respectively. Six patients (19%) receiving 5 mg b.i.d. and 11 (35%) receiving 10 mg b.i.d. discontinued marimastat therapy due to toxicity. Trough plasma levels were rarely within the target range for biological activity (40-200 ng/ml) with mean concentration for patients receiving: 5 mg b.i.d. = 7.5; 5 mg b.i.d. plus tamoxifen = 6.9; 10 mg b.i.d. = 11.9; 10 mg b.i.d. plus tamoxifen = 12.8. Conclusions: A randomized adjuvant trial with marimastat is not warranted as chronic administration cannot maintain plasma levels with the target range.

KW - Angiogenesis

KW - Breast cancer

KW - Metalloproteinase

KW - Metalloproteinase inhibitor

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