Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT‐1 and SALT‐2 trials
Abstract Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer‐related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT‐1 (Study of As...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.805 |
| _version_ | 1811212403610746880 |
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| author | Richard J. Gralla Fatima Ahmad Jaime D. Blais Joseph Chiodo III Wen Zhou Linda A. Glaser Frank S. Czerwiec |
| author_facet | Richard J. Gralla Fatima Ahmad Jaime D. Blais Joseph Chiodo III Wen Zhou Linda A. Glaser Frank S. Czerwiec |
| author_sort | Richard J. Gralla |
| collection | DOAJ |
| description | Abstract Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer‐related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT‐1 (Study of Ascending Levels of Tolvaptan in Hyponatremia) and SALT‐2 clinical trials. Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2‐receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once‐daily for 30 days. The initial tolvaptan dose (15 mg) was titrated over 4 days to 30 or 60 mg per day, as needed, according to serum sodium level and tolerability. Baseline serum sodium levels in the SIADH/cancer cohort of the SALT trials was 130 and 128 mEq/L for tolvaptan and placebo, respectively. Mean change from baseline in average daily serum sodium AUC for tolvaptan relative to placebo was 5.0 versus −0.3 mEq/L (P < 0.0001) at day 4, and 6.9 versus 1.0 mEq/L (P < 0.0001) at day 30; the observed treatment effects were similar to those in the overall SIADH population (i.e., with and without cancer) at both time points. Serum sodium normalization was observed in 6/12 and 0/13 subjects at day 4 and 7/8 and 2/6 subjects at day 30 in the tolvaptan and placebo groups, respectively (P < 0.05 for both). Common treatment‐emergent AEs for tolvaptan were consistent with previously reported results. In this post hoc study of the SALT trial population, oral tolvaptan was an effective and safe therapy for the treatment of hyponatremia in subjects with SIADH and cancer. |
| first_indexed | 2024-04-12T05:28:48Z |
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| id | doaj.art-570e8d00d02e4016b62d51039bc5fd90 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-12T05:28:48Z |
| publishDate | 2017-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-570e8d00d02e4016b62d51039bc5fd902022-12-22T03:46:10ZengWileyCancer Medicine2045-76342017-04-016472372910.1002/cam4.805Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT‐1 and SALT‐2 trialsRichard J. Gralla0Fatima Ahmad1Jaime D. Blais2Joseph Chiodo III3Wen Zhou4Linda A. Glaser5Frank S. Czerwiec6Albert Einstein College of Medicine Bronx New YorkOtsuka Pharmaceutical Development & Commercialization Inc. Rockville MarylandOtsuka Pharmaceutical Development & Commercialization Inc. Rockville MarylandOtsuka Pharmaceutical Development & Commercialization Inc. Rockville MarylandOtsuka Pharmaceutical Development & Commercialization Inc. Rockville MarylandCoastal Biomedical Research, Inc. Santa Monica CaliforniaOtsuka Pharmaceutical Development & Commercialization Inc. Rockville MarylandAbstract Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer‐related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT‐1 (Study of Ascending Levels of Tolvaptan in Hyponatremia) and SALT‐2 clinical trials. Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2‐receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once‐daily for 30 days. The initial tolvaptan dose (15 mg) was titrated over 4 days to 30 or 60 mg per day, as needed, according to serum sodium level and tolerability. Baseline serum sodium levels in the SIADH/cancer cohort of the SALT trials was 130 and 128 mEq/L for tolvaptan and placebo, respectively. Mean change from baseline in average daily serum sodium AUC for tolvaptan relative to placebo was 5.0 versus −0.3 mEq/L (P < 0.0001) at day 4, and 6.9 versus 1.0 mEq/L (P < 0.0001) at day 30; the observed treatment effects were similar to those in the overall SIADH population (i.e., with and without cancer) at both time points. Serum sodium normalization was observed in 6/12 and 0/13 subjects at day 4 and 7/8 and 2/6 subjects at day 30 in the tolvaptan and placebo groups, respectively (P < 0.05 for both). Common treatment‐emergent AEs for tolvaptan were consistent with previously reported results. In this post hoc study of the SALT trial population, oral tolvaptan was an effective and safe therapy for the treatment of hyponatremia in subjects with SIADH and cancer.https://doi.org/10.1002/cam4.805breast cancerhead and neck cancer,Hyponatremia,lung cancer,renal cancersyndrome of inappropriate antidiuretic hormone (SIADH) |
| spellingShingle | Richard J. Gralla Fatima Ahmad Jaime D. Blais Joseph Chiodo III Wen Zhou Linda A. Glaser Frank S. Czerwiec Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT‐1 and SALT‐2 trials Cancer Medicine breast cancer head and neck cancer, Hyponatremia, lung cancer, renal cancer syndrome of inappropriate antidiuretic hormone (SIADH) |
| title | Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT‐1 and SALT‐2 trials |
| title_full | Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT‐1 and SALT‐2 trials |
| title_fullStr | Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT‐1 and SALT‐2 trials |
| title_full_unstemmed | Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT‐1 and SALT‐2 trials |
| title_short | Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT‐1 and SALT‐2 trials |
| title_sort | tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone a post hoc analysis of the salt 1 and salt 2 trials |
| topic | breast cancer head and neck cancer, Hyponatremia, lung cancer, renal cancer syndrome of inappropriate antidiuretic hormone (SIADH) |
| url | https://doi.org/10.1002/cam4.805 |
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