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A phase II, randomized, double blind trial of calcium aluminosilicate clay versus placebo for the prevention of diarrhea in patients with metastatic colorectal cancer treated with irinotecan

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Abstract

Purpose

Calcium aluminosilicate clay (CASAD) is a naturally occurring clay that serves as a cation exchange absorbent. We hypothesized that oral administration of CASAD would reduce the rate of grade 3/4 diarrhea associated with irinotecan use for metastatic colorectal cancer (CRC) by adsorbing the SN-38 metabolite.

Methods

Patients receiving irinotecan-based chemotherapy were randomized equally between CASAD and placebo arms in this multicenter trial in order to assess differences in the proportions of patients with grade 3/4 diarrhea within 6 weeks. Additionally, we compared symptom severity between the two arms using the M.D. Anderson Symptom Inventory.

Results

Between May 2009 and May 2012, 100 patients were enrolled. In evaluable patients, 7 of 43 (16 %) on the CASAD arm compared to 3 of 32 (9 %) on the placebo arm experienced grade 3/4 diarrhea (P = 0.70). The rate of any diarrhea among all patients was similar (CASAD arm, 64 % vs. placebo arm, 70 %). The rate of study dropout was 14 % in the CASAD arm and 38 % in the placebo arm (P = 0.01). No differences were found in symptom severity, individual symptom items, and in serious adverse events between the two arms.

Conclusion

Compared to placebo, CASAD use was safe but ineffective in preventing diarrhea in metastatic CRC patients treated with irinotecan-containing chemotherapy regimens. There were no distinct signals in terms of patient symptoms between arms, but there was significantly more patient dropout in the placebo arm. Future CASAD trials will focus on the active treatment of diarrhea.

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Conflict of interest

This study was supported by the National Cancer Institute Grant U10 CA045809. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI. The study drug and placebo and additional funding for research nursing support were received by Dr. Fisch on behalf of the MD Anderson Community Clinical Oncology Program from Salient Pharmaceuticals. Dr. Fisch and the study team have full control of all of the primary data, and the Journal of Supportive Care in Cancer may review the data upon request.

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030, USA

    Bryan K. Kee & Michael Overman

  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jeffrey S. Morris & Rebecca S. Slack

  3. Columbia River Oncology Program, Portland, OR, USA

    Todd Crocenzi

  4. Scott & White Memorial Hospital, Temple, TX, USA

    Lucas Wong

  5. Central Illinois CCOP, Decatur, IL, USA

    Ben Esparaz

  6. Tyler Hematology-Oncology PA, Tyler, TX, USA

    Katrina Glover

  7. Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Desiree Jones & Michael J. Fisch

  8. Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, WV, USA

    Sijin Wen

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  1. Bryan K. Kee
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Correspondence to Bryan K. Kee.

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Kee, B.K., Morris, J.S., Slack, R.S. et al. A phase II, randomized, double blind trial of calcium aluminosilicate clay versus placebo for the prevention of diarrhea in patients with metastatic colorectal cancer treated with irinotecan. Support Care Cancer 23, 661–670 (2015). https://doi.org/10.1007/s00520-014-2402-1

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