Management of Hyponatremia in Cisplatin-Based Chemotherapy with Immunotherapy

Cisplatin-Specific Concerns with Hyponatremia

The American Society of Clinical Oncology (ASCO) guidelines specify that standard cisplatin dosing should be used with attempts to minimize dose reductions, particularly during the first two cycles, assuming normal organ function and electrolyte balance 1.
Cisplatin has FDA black box warnings for nephrotoxicity, and administering this agent in the setting of pre-existing hyponatremia substantially increases the risk of worsening renal function and severe electrolyte disturbances 1.
Hyponatremia itself may indicate underlying renal dysfunction, SIADH, or volume depletion, all of which increase cisplatin nephrotoxicity risk 1, 2.

The American Society of Clinical Oncology (ASCO) guidelines state that carboplatin and etoposide may be offered as systemic therapy concurrent with radiation for patients with contraindications to cisplatin, with a strong recommendation despite lower quality evidence 1.
If sodium cannot be rapidly corrected, carboplatin plus etoposide with atezolizumab is an acceptable alternative that avoids the heightened nephrotoxicity risk of cisplatin 1, 3, 4.
A meta-analysis of four randomized trials comparing cisplatin versus carboplatin-based chemotherapy demonstrated no difference in efficacy outcomes, including response rate, PFS, and overall survival, in extensive-stage SCLC 3, 4, 5.

Carboplatin causes more hematologic toxicity, particularly thrombocytopenia, but significantly less nephrotoxicity, neurotoxicity, and ototoxicity, compared to cisplatin 3, 4, 5.
The ASCO guidelines recommend monitoring electrolytes closely during treatment, as both cisplatin and carboplatin can cause hypomagnesemia and hypokalemia, which compound hyponatremia risks 1, 3.

Never administer cisplatin with sodium <130 mEq/L, as this dramatically increases the risk of acute kidney injury, severe hyponatremia, and potential seizures 1.
Do not delay treatment excessively trying to optimize for cisplatin if sodium correction is slow; carboplatin substitution provides equivalent survival benefit 3, 4.
Avoid assuming hyponatremia will self-correct, as in SCLC patients, SIADH is common and may require specific management (fluid restriction, salt tablets, or vasopressin receptor antagonists) 2.