Is bortezomib, a proteasome inhibitor, effective in treating cancer-associated weight loss? Preliminary results from the North Central Cancer Treatment Group

Aminah Jatoi, Steven Robert Alberts, Nathan Foster, Roscoe Morton, Patrick Burch, Margaret Block, Phuong L. Nguyen, John Kugler

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Weight loss predicts a poor prognosis for cancer patients, and previous studies have implicated the ubiquitin-proteasome pathway as a major mediator of cancer-associated weight loss. The recent emergence of bortezomib, a proteasome inhibitor, now allows testing on whether proteasome inhibition is effective therapy for cancer-associated weight loss. Methods: This study represents a subanalysis from two prior antineoplastic trials in patients with adenocarcinoma of the pancreas. The first included 46 patients with metastatic pancreatic cancer who were treated with single-agent bortezomib (intravenous doses of 1.5 or 1.3 mg/m 2 on days 1, 4, 8, and 11 of a 21-day cycle). The second included 42 patients with pancreatic cancer treated with single-agent octreotide (200 or 500 μg subcutaneously three times a day). The FACT-C questionnaire provided appetite and related data for bortezomib-treated patients. Serial weight data were available from both trials. Such data from the octreotide trial were utilized for comparative purposes because the latter holds no track record in treating cancer-associated weight loss. Results: Bortezomib- and octreotide-treated patients were roughly comparable at baseline, and neither agent demonstrated notable antineoplastic effects. FACT-C data suggested stable appetite, but high patient dropout rates invite caution in interpretation. For example, in response to "I have a good appetite," mean scores for bortezomib-treated patients were 45 at baseline (n=42), 45 at the end of cycle 1 (n=26), and 44 at the end of cycle 2 (n=9). In contrast, weight data appeared more straightforward to interpret: direct comparisons of mean change in weight from baseline between bortezomib- and octreotide-treated patients showed no significant differences between groups. Conclusions: These preliminary results suggest that bortezomib shows negligible favorable effects on cancer-associated weight loss in patients with metastatic pancreatic cancer. We conclude that further study of bortezomib specifically in this setting and for this indication is not warranted.

Original languageEnglish (US)
Pages (from-to)381-386
Number of pages6
JournalSupportive Care in Cancer
Volume13
Issue number6
DOIs
StatePublished - Jun 2005

Fingerprint

Proteasome Inhibitors
Weight Loss
Octreotide
Neoplasms
Appetite
Pancreatic Neoplasms
Therapeutics
Proteasome Endopeptidase Complex
Weights and Measures
Antineoplastic Agents
Bortezomib
Patient Dropouts
Second Primary Neoplasms
Ubiquitin
Pancreas
Adenocarcinoma

Keywords

  • Bortezomib
  • Cachexia
  • Cancer
  • Proteasome
  • Weight loss

ASJC Scopus subject areas

  • Oncology
  • Nursing(all)

Cite this

Is bortezomib, a proteasome inhibitor, effective in treating cancer-associated weight loss? Preliminary results from the North Central Cancer Treatment Group. / Jatoi, Aminah; Alberts, Steven Robert; Foster, Nathan; Morton, Roscoe; Burch, Patrick; Block, Margaret; Nguyen, Phuong L.; Kugler, John.

In: Supportive Care in Cancer, Vol. 13, No. 6, 06.2005, p. 381-386.

Research output: Contribution to journalArticle

Jatoi, Aminah ; Alberts, Steven Robert ; Foster, Nathan ; Morton, Roscoe ; Burch, Patrick ; Block, Margaret ; Nguyen, Phuong L. ; Kugler, John. / Is bortezomib, a proteasome inhibitor, effective in treating cancer-associated weight loss? Preliminary results from the North Central Cancer Treatment Group. In: Supportive Care in Cancer. 2005 ; Vol. 13, No. 6. pp. 381-386.
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T1 - Is bortezomib, a proteasome inhibitor, effective in treating cancer-associated weight loss? Preliminary results from the North Central Cancer Treatment Group

AU - Jatoi, Aminah

AU - Alberts, Steven Robert

AU - Foster, Nathan

AU - Morton, Roscoe

AU - Burch, Patrick

AU - Block, Margaret

AU - Nguyen, Phuong L.

AU - Kugler, John

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N2 - Background: Weight loss predicts a poor prognosis for cancer patients, and previous studies have implicated the ubiquitin-proteasome pathway as a major mediator of cancer-associated weight loss. The recent emergence of bortezomib, a proteasome inhibitor, now allows testing on whether proteasome inhibition is effective therapy for cancer-associated weight loss. Methods: This study represents a subanalysis from two prior antineoplastic trials in patients with adenocarcinoma of the pancreas. The first included 46 patients with metastatic pancreatic cancer who were treated with single-agent bortezomib (intravenous doses of 1.5 or 1.3 mg/m 2 on days 1, 4, 8, and 11 of a 21-day cycle). The second included 42 patients with pancreatic cancer treated with single-agent octreotide (200 or 500 μg subcutaneously three times a day). The FACT-C questionnaire provided appetite and related data for bortezomib-treated patients. Serial weight data were available from both trials. Such data from the octreotide trial were utilized for comparative purposes because the latter holds no track record in treating cancer-associated weight loss. Results: Bortezomib- and octreotide-treated patients were roughly comparable at baseline, and neither agent demonstrated notable antineoplastic effects. FACT-C data suggested stable appetite, but high patient dropout rates invite caution in interpretation. For example, in response to "I have a good appetite," mean scores for bortezomib-treated patients were 45 at baseline (n=42), 45 at the end of cycle 1 (n=26), and 44 at the end of cycle 2 (n=9). In contrast, weight data appeared more straightforward to interpret: direct comparisons of mean change in weight from baseline between bortezomib- and octreotide-treated patients showed no significant differences between groups. Conclusions: These preliminary results suggest that bortezomib shows negligible favorable effects on cancer-associated weight loss in patients with metastatic pancreatic cancer. We conclude that further study of bortezomib specifically in this setting and for this indication is not warranted.

AB - Background: Weight loss predicts a poor prognosis for cancer patients, and previous studies have implicated the ubiquitin-proteasome pathway as a major mediator of cancer-associated weight loss. The recent emergence of bortezomib, a proteasome inhibitor, now allows testing on whether proteasome inhibition is effective therapy for cancer-associated weight loss. Methods: This study represents a subanalysis from two prior antineoplastic trials in patients with adenocarcinoma of the pancreas. The first included 46 patients with metastatic pancreatic cancer who were treated with single-agent bortezomib (intravenous doses of 1.5 or 1.3 mg/m 2 on days 1, 4, 8, and 11 of a 21-day cycle). The second included 42 patients with pancreatic cancer treated with single-agent octreotide (200 or 500 μg subcutaneously three times a day). The FACT-C questionnaire provided appetite and related data for bortezomib-treated patients. Serial weight data were available from both trials. Such data from the octreotide trial were utilized for comparative purposes because the latter holds no track record in treating cancer-associated weight loss. Results: Bortezomib- and octreotide-treated patients were roughly comparable at baseline, and neither agent demonstrated notable antineoplastic effects. FACT-C data suggested stable appetite, but high patient dropout rates invite caution in interpretation. For example, in response to "I have a good appetite," mean scores for bortezomib-treated patients were 45 at baseline (n=42), 45 at the end of cycle 1 (n=26), and 44 at the end of cycle 2 (n=9). In contrast, weight data appeared more straightforward to interpret: direct comparisons of mean change in weight from baseline between bortezomib- and octreotide-treated patients showed no significant differences between groups. Conclusions: These preliminary results suggest that bortezomib shows negligible favorable effects on cancer-associated weight loss in patients with metastatic pancreatic cancer. We conclude that further study of bortezomib specifically in this setting and for this indication is not warranted.

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