A randomized, double-blind, placebo-controlled trial of a β-hydroxyl β-methyl butyrate, glutamine, and arginine mixture for the treatment of cancer cachexia (RTOG 0122)

Lawrence Berk, Jennifer James, Anna Schwartz, Eugen Hug, Anand Mahadevan, Michael A Samuels, Lisa Kachnic

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Purpose: Cancer cachexia is a common problem among advanced cancer patients. A mixture of β-hydroxyl β-methyl butyrate, glutamine, and arginine (HMB/Arg/Gln) previously showed activity for increasing lean body mass (LBM) among patients with cancer cachexia. Therefore a phase III trial was implemented to confirm this activity. Materials and methods: Four hundred seventy-two advanced cancer patients with between 2% and 10% weight loss were randomized to a mixture of β-hydroxyl β-methyl butyrate, glutamine, and arginine or an isonitrogenous, isocaloric control mixture taken twice a day for 8 weeks. Lean body mass was estimated by bioimpedance and skin-fold measurements. Body plethysmography was used when available. Weight, the Schwartz Fatigue Scale, and the Spitzer Quality of Life Scale were also measured. Results: Only 37% of the patients completed protocol treatment. The majority of the patient loss was because of patient preference (45% of enrolled patients). However, loss of power was not an issue because of the planned large target sample size. Based on an intention to treat analysis, there was no statistically significant difference in the 8-week lean body mass between the two arms. The secondary endpoints were also not significantly different between the arms. Based on the results of the area under the curve (AUC) analysis, patients receiving HMB/Arg/Gln had a strong trend higher LBM throughout the study as measured by both bioimpedance (p=0.08) and skin-fold measurements (p=0.08). Among the subset of patients receiving concurrent chemotherapy, there were again no significant differences in the endpoints. The secondary endpoints were also not significantly different between the arms. Conclusion: This trial was unable to adequately test the ability of β-hydroxy β-methylbutyrate, glutamine, and arginine to reverse or prevent lean body mass wasting among cancer patients. Possible contributing factors beyond the efficacy of the intervention were the inability of patients to complete an 8-week course of treatment and return in a timely fashion for follow-up assessment, and because the patients may have only had weight loss possible not related to cachexia, but other causes of weight loss, such as decreased appetite. However, there was a strong trend towards an increased body mass among patients taking the Juven® compound using the secondary endpoint of AUC.

Original languageEnglish
Pages (from-to)1179-1188
Number of pages10
JournalSupportive Care in Cancer
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2008

Fingerprint

Cachexia
Glutamine
Hydroxyl Radical
Arginine
Placebos
Neoplasms
Therapeutics
Weight Loss
Area Under Curve
methyl butyrate
Skin
Intention to Treat Analysis
Aptitude
Plethysmography
Patient Preference
Appetite
Clinical Protocols
Sample Size
Fatigue

Keywords

  • Cachexia
  • Cancer
  • Quality of life
  • Randomized trial
  • Weight loss

ASJC Scopus subject areas

  • Oncology
  • Nursing(all)

Cite this

A randomized, double-blind, placebo-controlled trial of a β-hydroxyl β-methyl butyrate, glutamine, and arginine mixture for the treatment of cancer cachexia (RTOG 0122). / Berk, Lawrence; James, Jennifer; Schwartz, Anna; Hug, Eugen; Mahadevan, Anand; Samuels, Michael A; Kachnic, Lisa.

In: Supportive Care in Cancer, Vol. 16, No. 10, 01.10.2008, p. 1179-1188.

Research output: Contribution to journalArticle

Berk, Lawrence ; James, Jennifer ; Schwartz, Anna ; Hug, Eugen ; Mahadevan, Anand ; Samuels, Michael A ; Kachnic, Lisa. / A randomized, double-blind, placebo-controlled trial of a β-hydroxyl β-methyl butyrate, glutamine, and arginine mixture for the treatment of cancer cachexia (RTOG 0122). In: Supportive Care in Cancer. 2008 ; Vol. 16, No. 10. pp. 1179-1188.
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abstract = "Purpose: Cancer cachexia is a common problem among advanced cancer patients. A mixture of β-hydroxyl β-methyl butyrate, glutamine, and arginine (HMB/Arg/Gln) previously showed activity for increasing lean body mass (LBM) among patients with cancer cachexia. Therefore a phase III trial was implemented to confirm this activity. Materials and methods: Four hundred seventy-two advanced cancer patients with between 2{\%} and 10{\%} weight loss were randomized to a mixture of β-hydroxyl β-methyl butyrate, glutamine, and arginine or an isonitrogenous, isocaloric control mixture taken twice a day for 8 weeks. Lean body mass was estimated by bioimpedance and skin-fold measurements. Body plethysmography was used when available. Weight, the Schwartz Fatigue Scale, and the Spitzer Quality of Life Scale were also measured. Results: Only 37{\%} of the patients completed protocol treatment. The majority of the patient loss was because of patient preference (45{\%} of enrolled patients). However, loss of power was not an issue because of the planned large target sample size. Based on an intention to treat analysis, there was no statistically significant difference in the 8-week lean body mass between the two arms. The secondary endpoints were also not significantly different between the arms. Based on the results of the area under the curve (AUC) analysis, patients receiving HMB/Arg/Gln had a strong trend higher LBM throughout the study as measured by both bioimpedance (p=0.08) and skin-fold measurements (p=0.08). Among the subset of patients receiving concurrent chemotherapy, there were again no significant differences in the endpoints. The secondary endpoints were also not significantly different between the arms. Conclusion: This trial was unable to adequately test the ability of β-hydroxy β-methylbutyrate, glutamine, and arginine to reverse or prevent lean body mass wasting among cancer patients. Possible contributing factors beyond the efficacy of the intervention were the inability of patients to complete an 8-week course of treatment and return in a timely fashion for follow-up assessment, and because the patients may have only had weight loss possible not related to cachexia, but other causes of weight loss, such as decreased appetite. However, there was a strong trend towards an increased body mass among patients taking the Juven{\circledR} compound using the secondary endpoint of AUC.",
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AU - James, Jennifer

AU - Schwartz, Anna

AU - Hug, Eugen

AU - Mahadevan, Anand

AU - Samuels, Michael A

AU - Kachnic, Lisa

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N2 - Purpose: Cancer cachexia is a common problem among advanced cancer patients. A mixture of β-hydroxyl β-methyl butyrate, glutamine, and arginine (HMB/Arg/Gln) previously showed activity for increasing lean body mass (LBM) among patients with cancer cachexia. Therefore a phase III trial was implemented to confirm this activity. Materials and methods: Four hundred seventy-two advanced cancer patients with between 2% and 10% weight loss were randomized to a mixture of β-hydroxyl β-methyl butyrate, glutamine, and arginine or an isonitrogenous, isocaloric control mixture taken twice a day for 8 weeks. Lean body mass was estimated by bioimpedance and skin-fold measurements. Body plethysmography was used when available. Weight, the Schwartz Fatigue Scale, and the Spitzer Quality of Life Scale were also measured. Results: Only 37% of the patients completed protocol treatment. The majority of the patient loss was because of patient preference (45% of enrolled patients). However, loss of power was not an issue because of the planned large target sample size. Based on an intention to treat analysis, there was no statistically significant difference in the 8-week lean body mass between the two arms. The secondary endpoints were also not significantly different between the arms. Based on the results of the area under the curve (AUC) analysis, patients receiving HMB/Arg/Gln had a strong trend higher LBM throughout the study as measured by both bioimpedance (p=0.08) and skin-fold measurements (p=0.08). Among the subset of patients receiving concurrent chemotherapy, there were again no significant differences in the endpoints. The secondary endpoints were also not significantly different between the arms. Conclusion: This trial was unable to adequately test the ability of β-hydroxy β-methylbutyrate, glutamine, and arginine to reverse or prevent lean body mass wasting among cancer patients. Possible contributing factors beyond the efficacy of the intervention were the inability of patients to complete an 8-week course of treatment and return in a timely fashion for follow-up assessment, and because the patients may have only had weight loss possible not related to cachexia, but other causes of weight loss, such as decreased appetite. However, there was a strong trend towards an increased body mass among patients taking the Juven® compound using the secondary endpoint of AUC.

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KW - Cancer

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