A randomized trial of tamoxifen alone or combined with octreotide in the treatment of women with metastatic breast carcinoma

James N. Ingle, Vera Jean Suman, Carl G. Kardinal, James E. Krook, James A. Mailliard, Michael H. Veeder, Charles Lawrence Loprinzi, Robert J. Dalton, Lynn C. Hartmann, Cheryl A Conover, Michael N. Pollak

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Abstract

BACKGROUND. Tamoxifen (TAM) is generally considered the hormonal agent of choice for postmenopausal women with hormone receptor positive breast carcinoma. The somatostatin analogues, including octreotide, have demonstrated inhibition of breast carcinoma cell lines and multiple endocrinologic actions, including reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast carcinoma cells. In an attempt to improve the efficacy of TAM, this randomized trial was performed. METHODS. One hundred thirty-five eligible postmenopausal women with metastatic breast carcinoma were randomized to TAM (10 mg twice daily) alone or combined with octreotide 150 μg (administered subcutaneously thrice daily). The two groups were well balanced, except the TAM group had higher proportions of patients with visceral disease (50% vs. 37%) and a disease free interval longer than 5 years (47% vs. 34%). A cohort of 18 patients was evaluated for the impact of treatment on serum IGF-I, free IGF-I, IGF binding protein 3 levels, and total IGF binding capacity. RESULTS. The median time to progression was estimated to be 14.2 months with TAM and 10.3 months with TAM plus octreotide. The distribution of progression free survival times revealed no significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM + octreotide) was 0.81 (95% confidence interval [CI], 0.56-1.17). The distribution of survival times revealed no significant difference (P = 0.92), and the death hazard ratio was 0.98 (95% CI, 0.62-1.55). When the 106 patients with measurable or evaluable disease were considered, the objective response rate was 49% with TAM alone and 43% with TAM plus octreotide (P = 0.70). Patients who received TAM plus octreotide had higher incidences of nausea, diarrhea, and steatorrhea. The percentage of decline in serum IGF-I, from pretreatment levels to those following 3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM plus octreotide than with TAM alone. CONCLUSIONS. There is no indication that the combination of TAM plus octreotide as administered in this study is substantially more efficacious than TAM alone in the treatment of postmenopausal women with metastatic breast carcinoma. The limited cohort included in IGF-I studies suggests that TAM plus octreotide produces a significantly greater reduction in serum IGF- I levels.

Original languageEnglish (US)
Pages (from-to)1284-1292
Number of pages9
JournalCancer
Volume85
Issue number6
DOIs
StatePublished - Mar 15 1999

Fingerprint

Octreotide
Tamoxifen
Breast Neoplasms
Insulin-Like Growth Factor I
Therapeutics
Serum
Confidence Intervals
Steatorrhea
Insulin-Like Growth Factor Binding Protein 3
Somatostatin
Mitogens

Keywords

  • Breast carcinoma
  • Hormonal
  • Insulin- like growth factor I
  • Metastatic
  • Octreotide
  • Postmenopausal
  • Tamoxifen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A randomized trial of tamoxifen alone or combined with octreotide in the treatment of women with metastatic breast carcinoma. / Ingle, James N.; Suman, Vera Jean; Kardinal, Carl G.; Krook, James E.; Mailliard, James A.; Veeder, Michael H.; Loprinzi, Charles Lawrence; Dalton, Robert J.; Hartmann, Lynn C.; Conover, Cheryl A; Pollak, Michael N.

In: Cancer, Vol. 85, No. 6, 15.03.1999, p. 1284-1292.

Research output: Contribution to journalArticle

Ingle, James N. ; Suman, Vera Jean ; Kardinal, Carl G. ; Krook, James E. ; Mailliard, James A. ; Veeder, Michael H. ; Loprinzi, Charles Lawrence ; Dalton, Robert J. ; Hartmann, Lynn C. ; Conover, Cheryl A ; Pollak, Michael N. / A randomized trial of tamoxifen alone or combined with octreotide in the treatment of women with metastatic breast carcinoma. In: Cancer. 1999 ; Vol. 85, No. 6. pp. 1284-1292.
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abstract = "BACKGROUND. Tamoxifen (TAM) is generally considered the hormonal agent of choice for postmenopausal women with hormone receptor positive breast carcinoma. The somatostatin analogues, including octreotide, have demonstrated inhibition of breast carcinoma cell lines and multiple endocrinologic actions, including reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast carcinoma cells. In an attempt to improve the efficacy of TAM, this randomized trial was performed. METHODS. One hundred thirty-five eligible postmenopausal women with metastatic breast carcinoma were randomized to TAM (10 mg twice daily) alone or combined with octreotide 150 μg (administered subcutaneously thrice daily). The two groups were well balanced, except the TAM group had higher proportions of patients with visceral disease (50{\%} vs. 37{\%}) and a disease free interval longer than 5 years (47{\%} vs. 34{\%}). A cohort of 18 patients was evaluated for the impact of treatment on serum IGF-I, free IGF-I, IGF binding protein 3 levels, and total IGF binding capacity. RESULTS. The median time to progression was estimated to be 14.2 months with TAM and 10.3 months with TAM plus octreotide. The distribution of progression free survival times revealed no significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM + octreotide) was 0.81 (95{\%} confidence interval [CI], 0.56-1.17). The distribution of survival times revealed no significant difference (P = 0.92), and the death hazard ratio was 0.98 (95{\%} CI, 0.62-1.55). When the 106 patients with measurable or evaluable disease were considered, the objective response rate was 49{\%} with TAM alone and 43{\%} with TAM plus octreotide (P = 0.70). Patients who received TAM plus octreotide had higher incidences of nausea, diarrhea, and steatorrhea. The percentage of decline in serum IGF-I, from pretreatment levels to those following 3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM plus octreotide than with TAM alone. CONCLUSIONS. There is no indication that the combination of TAM plus octreotide as administered in this study is substantially more efficacious than TAM alone in the treatment of postmenopausal women with metastatic breast carcinoma. The limited cohort included in IGF-I studies suggests that TAM plus octreotide produces a significantly greater reduction in serum IGF- I levels.",
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author = "Ingle, {James N.} and Suman, {Vera Jean} and Kardinal, {Carl G.} and Krook, {James E.} and Mailliard, {James A.} and Veeder, {Michael H.} and Loprinzi, {Charles Lawrence} and Dalton, {Robert J.} and Hartmann, {Lynn C.} and Conover, {Cheryl A} and Pollak, {Michael N.}",
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TY - JOUR

T1 - A randomized trial of tamoxifen alone or combined with octreotide in the treatment of women with metastatic breast carcinoma

AU - Ingle, James N.

AU - Suman, Vera Jean

AU - Kardinal, Carl G.

AU - Krook, James E.

AU - Mailliard, James A.

AU - Veeder, Michael H.

AU - Loprinzi, Charles Lawrence

AU - Dalton, Robert J.

AU - Hartmann, Lynn C.

AU - Conover, Cheryl A

AU - Pollak, Michael N.

PY - 1999/3/15

Y1 - 1999/3/15

N2 - BACKGROUND. Tamoxifen (TAM) is generally considered the hormonal agent of choice for postmenopausal women with hormone receptor positive breast carcinoma. The somatostatin analogues, including octreotide, have demonstrated inhibition of breast carcinoma cell lines and multiple endocrinologic actions, including reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast carcinoma cells. In an attempt to improve the efficacy of TAM, this randomized trial was performed. METHODS. One hundred thirty-five eligible postmenopausal women with metastatic breast carcinoma were randomized to TAM (10 mg twice daily) alone or combined with octreotide 150 μg (administered subcutaneously thrice daily). The two groups were well balanced, except the TAM group had higher proportions of patients with visceral disease (50% vs. 37%) and a disease free interval longer than 5 years (47% vs. 34%). A cohort of 18 patients was evaluated for the impact of treatment on serum IGF-I, free IGF-I, IGF binding protein 3 levels, and total IGF binding capacity. RESULTS. The median time to progression was estimated to be 14.2 months with TAM and 10.3 months with TAM plus octreotide. The distribution of progression free survival times revealed no significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM + octreotide) was 0.81 (95% confidence interval [CI], 0.56-1.17). The distribution of survival times revealed no significant difference (P = 0.92), and the death hazard ratio was 0.98 (95% CI, 0.62-1.55). When the 106 patients with measurable or evaluable disease were considered, the objective response rate was 49% with TAM alone and 43% with TAM plus octreotide (P = 0.70). Patients who received TAM plus octreotide had higher incidences of nausea, diarrhea, and steatorrhea. The percentage of decline in serum IGF-I, from pretreatment levels to those following 3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM plus octreotide than with TAM alone. CONCLUSIONS. There is no indication that the combination of TAM plus octreotide as administered in this study is substantially more efficacious than TAM alone in the treatment of postmenopausal women with metastatic breast carcinoma. The limited cohort included in IGF-I studies suggests that TAM plus octreotide produces a significantly greater reduction in serum IGF- I levels.

AB - BACKGROUND. Tamoxifen (TAM) is generally considered the hormonal agent of choice for postmenopausal women with hormone receptor positive breast carcinoma. The somatostatin analogues, including octreotide, have demonstrated inhibition of breast carcinoma cell lines and multiple endocrinologic actions, including reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast carcinoma cells. In an attempt to improve the efficacy of TAM, this randomized trial was performed. METHODS. One hundred thirty-five eligible postmenopausal women with metastatic breast carcinoma were randomized to TAM (10 mg twice daily) alone or combined with octreotide 150 μg (administered subcutaneously thrice daily). The two groups were well balanced, except the TAM group had higher proportions of patients with visceral disease (50% vs. 37%) and a disease free interval longer than 5 years (47% vs. 34%). A cohort of 18 patients was evaluated for the impact of treatment on serum IGF-I, free IGF-I, IGF binding protein 3 levels, and total IGF binding capacity. RESULTS. The median time to progression was estimated to be 14.2 months with TAM and 10.3 months with TAM plus octreotide. The distribution of progression free survival times revealed no significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM + octreotide) was 0.81 (95% confidence interval [CI], 0.56-1.17). The distribution of survival times revealed no significant difference (P = 0.92), and the death hazard ratio was 0.98 (95% CI, 0.62-1.55). When the 106 patients with measurable or evaluable disease were considered, the objective response rate was 49% with TAM alone and 43% with TAM plus octreotide (P = 0.70). Patients who received TAM plus octreotide had higher incidences of nausea, diarrhea, and steatorrhea. The percentage of decline in serum IGF-I, from pretreatment levels to those following 3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM plus octreotide than with TAM alone. CONCLUSIONS. There is no indication that the combination of TAM plus octreotide as administered in this study is substantially more efficacious than TAM alone in the treatment of postmenopausal women with metastatic breast carcinoma. The limited cohort included in IGF-I studies suggests that TAM plus octreotide produces a significantly greater reduction in serum IGF- I levels.

KW - Breast carcinoma

KW - Hormonal

KW - Insulin- like growth factor I

KW - Metastatic

KW - Octreotide

KW - Postmenopausal

KW - Tamoxifen

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