Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma

James B. Berenson, Sundar Jagannath, Bart Barlogie, David T. Siegel, Raymond Alexanian, Paul G. Richardson, David Irwin, Melissa Alsina, S Vincent Rajkumar, Gordon Srkalovic, Seema Singhal, Steven Limenitani, Ruben Niesvizky, Dixie L. Esseltine, Elizabeth Trehu, David P. Schenkein, Kenneth Anderson

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Abstract

BACKGROUND. Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma. METHODS. Bortezomib 1.0 or 1.3 mg/m2 was administered Days 1, 4, 8, and 11 every 21 days for up to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone could be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment. RESULTS. Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89%. Overall, 75% of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension and parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29%), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11%), anemia (11%), and neutropenia (10%). Neuropathy was reported less frequently. CONCLUSIONS. Retreatment with or continuation of bortezomib ± dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma.

Original languageEnglish (US)
Pages (from-to)2141-2148
Number of pages8
JournalCancer
Volume104
Issue number10
DOIs
StatePublished - Nov 15 2005

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Multiple Myeloma
Safety
Dexamethasone
Retreatment
Therapeutics
Proteasome Inhibitors
Neutropenia
Thrombocytopenia
Bortezomib
Anemia
Diarrhea
Appointments and Schedules
Research Personnel

Keywords

  • Bortezomib
  • CREST
  • Extension
  • Myelomas
  • Proteasome
  • SUMMIT

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Berenson, J. B., Jagannath, S., Barlogie, B., Siegel, D. T., Alexanian, R., Richardson, P. G., ... Anderson, K. (2005). Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma. Cancer, 104(10), 2141-2148. https://doi.org/10.1002/cncr.21427

Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma. / Berenson, James B.; Jagannath, Sundar; Barlogie, Bart; Siegel, David T.; Alexanian, Raymond; Richardson, Paul G.; Irwin, David; Alsina, Melissa; Rajkumar, S Vincent; Srkalovic, Gordon; Singhal, Seema; Limenitani, Steven; Niesvizky, Ruben; Esseltine, Dixie L.; Trehu, Elizabeth; Schenkein, David P.; Anderson, Kenneth.

In: Cancer, Vol. 104, No. 10, 15.11.2005, p. 2141-2148.

Research output: Contribution to journalArticle

Berenson, JB, Jagannath, S, Barlogie, B, Siegel, DT, Alexanian, R, Richardson, PG, Irwin, D, Alsina, M, Rajkumar, SV, Srkalovic, G, Singhal, S, Limenitani, S, Niesvizky, R, Esseltine, DL, Trehu, E, Schenkein, DP & Anderson, K 2005, 'Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma', Cancer, vol. 104, no. 10, pp. 2141-2148. https://doi.org/10.1002/cncr.21427
Berenson JB, Jagannath S, Barlogie B, Siegel DT, Alexanian R, Richardson PG et al. Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma. Cancer. 2005 Nov 15;104(10):2141-2148. https://doi.org/10.1002/cncr.21427
Berenson, James B. ; Jagannath, Sundar ; Barlogie, Bart ; Siegel, David T. ; Alexanian, Raymond ; Richardson, Paul G. ; Irwin, David ; Alsina, Melissa ; Rajkumar, S Vincent ; Srkalovic, Gordon ; Singhal, Seema ; Limenitani, Steven ; Niesvizky, Ruben ; Esseltine, Dixie L. ; Trehu, Elizabeth ; Schenkein, David P. ; Anderson, Kenneth. / Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma. In: Cancer. 2005 ; Vol. 104, No. 10. pp. 2141-2148.
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abstract = "BACKGROUND. Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma. METHODS. Bortezomib 1.0 or 1.3 mg/m2 was administered Days 1, 4, 8, and 11 every 21 days for up to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone could be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment. RESULTS. Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89{\%}. Overall, 75{\%} of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension and parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29{\%}), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11{\%}), anemia (11{\%}), and neutropenia (10{\%}). Neuropathy was reported less frequently. CONCLUSIONS. Retreatment with or continuation of bortezomib ± dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma.",
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T1 - Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma

AU - Berenson, James B.

AU - Jagannath, Sundar

AU - Barlogie, Bart

AU - Siegel, David T.

AU - Alexanian, Raymond

AU - Richardson, Paul G.

AU - Irwin, David

AU - Alsina, Melissa

AU - Rajkumar, S Vincent

AU - Srkalovic, Gordon

AU - Singhal, Seema

AU - Limenitani, Steven

AU - Niesvizky, Ruben

AU - Esseltine, Dixie L.

AU - Trehu, Elizabeth

AU - Schenkein, David P.

AU - Anderson, Kenneth

PY - 2005/11/15

Y1 - 2005/11/15

N2 - BACKGROUND. Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma. METHODS. Bortezomib 1.0 or 1.3 mg/m2 was administered Days 1, 4, 8, and 11 every 21 days for up to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone could be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment. RESULTS. Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89%. Overall, 75% of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension and parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29%), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11%), anemia (11%), and neutropenia (10%). Neuropathy was reported less frequently. CONCLUSIONS. Retreatment with or continuation of bortezomib ± dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma.

AB - BACKGROUND. Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma. METHODS. Bortezomib 1.0 or 1.3 mg/m2 was administered Days 1, 4, 8, and 11 every 21 days for up to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone could be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment. RESULTS. Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89%. Overall, 75% of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension and parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29%), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11%), anemia (11%), and neutropenia (10%). Neuropathy was reported less frequently. CONCLUSIONS. Retreatment with or continuation of bortezomib ± dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma.

KW - Bortezomib

KW - CREST

KW - Extension

KW - Myelomas

KW - Proteasome

KW - SUMMIT

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