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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)

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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® compound using the secondary endpoint of AUC.

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Authors and Affiliations

  1. Moffitt Cancer Center at Tampa General Hospital, 2 Columbia Dr., Tampa, FL, 33606, USA

    Lawrence Berk

  2. Radiation Therapy Oncology Group Statistics Branch, 1818 Market St. Suite 1600, Philadelphia, PA, 19103, USA

    Jennifer James

  3. Scottsdale Health Care Research, Arizona State University, P.O. Box 1708, Cave Creek, AZ, 85237, USA

    Anna Schwartz

  4. Norris Cotton Cancer Center, 1 Medical Center Dr., Lebanon, NH, 03756, USA

    Eugen Hug

  5. Taussig Cancer Center, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    Anand Mahadevan

  6. Mt. Sinai CCOP, Mt. Sinai Medical Center, 4300 Alton Rd., Miami Beach, FL, 33140, USA

    Michael Samuels

  7. Radiation Oncology, Boston Medical Center, One Boston Medical Center Place, Boston, MA, 02118, USA

    Lisa Kachnic

Authors
  1. Lawrence Berk
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  2. Jennifer James
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  3. Anna Schwartz
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  4. Eugen Hug
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  5. Anand Mahadevan
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  6. Michael Samuels
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  7. Lisa Kachnic
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Correspondence to Lawrence Berk.

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Berk, L., James, J., Schwartz, A. et al. 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). Support Care Cancer 16, 1179–1188 (2008). https://doi.org/10.1007/s00520-008-0403-7

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  • DOI: https://doi.org/10.1007/s00520-008-0403-7

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