Cisplatin
Platinol · Platinum agent
Proximal tubular ATN + magnesium wasting; the archetype.
ATNLYTEPRE
SevereOpen →
Marine alkylating agent
Lurbinectedin
Zepzelca · LURB
A synthetic ecteinascidin for small-cell lung cancer whose rare renal injury follows rhabdomyolysis or tumor lysis.
MildMarine alkylating agent (ecteinascidin) · approved 2020
Metastatic small-cell lung cancer with disease progression on or after platinum-based chemotherapy
Signature kidney injury
Acute Tubular Necrosis
Not directly tubulotoxic; clinically significant AKI is rare and arises from rhabdomyolysis or tumor lysis. Rhabdomyolysis was formally recognized post-approval (FDA FAERS) and as an isolated phase 1 dose-limiting toxicity; the trial rate is not quantified. The dominant toxicity is hematologic (grade >=3 neutropenia ~41%) with frequent transaminase elevations.
Source: Trigo et al., Lancet Oncol 2020
Mechanism of kidney injury
Indirect: drug-induced rhabdomyolysis releases myoglobin causing pigment nephropathy/ATN (proximal tubular injury, intratubular cast obstruction and vasoconstriction). Tumor lysis is an alternate route to crystal/uric-acid nephropathy. The agent is not a recognized direct tubular toxin.
Clinical presentation
CK elevation with myalgia/weakness and dark urine, plus a rising creatinine; transaminase elevations are common and often concurrent. When tumor lysis drives AKI, expect hyperuricemia/hyperphosphatemia/hyperkalemia.
Onset
Variable across cycles (not tightly defined) — monitor with each dose.
Reversibility
Reversible
Anticancer mechanism
Synthetic ecteinascidin analog that binds the DNA minor groove and alkylates guanine N2 at CG-rich regulatory regions, stalling elongating RNA polymerase II and triggering its ubiquitination and proteasomal degradation; this induces double-strand breaks and suppresses oncogenic transcription and tumor-associated macrophages.
Management
For rhabdomyolysis: withhold/discontinue, give IV volume resuscitation, and correct hyperkalemia and metabolic derangements, with renal replacement therapy for refractory AKI. Standard tumor-lysis measures if applicable. Manage neutropenia with growth factors.
Risk factors
- Pre-existing renal impairment and volume depletion
- Concurrent myotoxic/nephrotoxic drugs (e.g. statins)
- High tumor burden (tumor lysis risk)
- Hepatic impairment
Prevention
- Baseline and periodic CK and renal monitoring; check CK with muscle symptoms
- Hydration; G-CSF prophylaxis for neutropenia
- Avoid extravasation (vesicant — prefer a secure/central line)
- Tumor-lysis prophylaxis in high-burden disease
Note · Recent (2020) accelerated approval; renal events are uncommon and largely post-marketing/case-level, with mechanism inferred from the rhabdomyolysis/tumor-lysis pathways.
Clinical depth
Renal dose adjustment
Standard 3.2 mg/m2 IV over 1 h every 3 weeks; dose reductions to 2.6 then 2.0 mg/m2 for toxicity. No dedicated renal adjustment for mild-moderate impairment; severe renal/hepatic impairment has not been studied, so CrCl cutoffs are not established.
Dialyzability & ESKD dosing
Not characterized; high protein binding and a large volume of distribution make significant dialytic removal unlikely. Dialysis would be used to support AKI, not to clear drug.
Differential diagnosis
Rhabdomyolysis/pigment nephropathy versus tumor lysis, prerenal volume depletion, concomitant nephrotoxins and sepsis-associated ATN. CK plus myoglobinuria identifies the pigment mechanism.
Monitoring
- CBC (neutropenia is the dominant toxicity), per-cycle and as indicated
- CK/CPK with any muscle symptoms
- LFTs each cycle
- Creatinine, electrolytes and tumor-lysis labs in high-burden disease
Key trials & series
- Trigo phase 2 basket trial (Lancet Oncol 2020) — pivotal SCLC trial supporting accelerated approval
- FDA FAERS analysis (Kaland, Clin Lung Cancer 2022) — formally identified rhabdomyolysis and tumor lysis
Clinical pearls
- Renal risk is indirect — an unexplained creatinine bump with myalgia or dark urine should prompt a CK.
- The FDA added rhabdomyolysis and tumor lysis to the label post-approval — keep both on the differential.
- Lurbinectedin is a vesicant — use a secure or central line.
- The confirmatory ATLANTIS combination was negative for overall survival; single-agent 3.2 mg/m2 remains standard.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Tubular Lumen
The urine flow path
Injury signatures
Acute Tubular NecrosisElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of marine alkylating agents.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
Evidence
7 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkLurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial.Trigo J et al. · Lancet Oncol 2020 · PMID 32224306Pivotal phase 2 SCLC basket trial supporting 2020 accelerated approval.PMIDCombination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial.Aix SP et al. · Lancet Respir Med 2022 · PMID 36252599Confirmatory phase 3 trial (negative for overall survival).PMIDU.S. Food and Drug Administration Analysis of Newly Identified Adverse Events With Lurbinectedin: Extravasation, Rhabdomyolysis, and Tumor Lysis Syndrome.Kaland DA et al. · Clin Lung Cancer 2022 · PMID 36151005FDA pharmacovigilance series formally identifying rhabdomyolysis (with AKI) and tumor lysis.PMIDPooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours.Leary A et al. · Eur J Cancer 2023 · PMID 37634282Largest pooled safety dataset quantifying hematologic and transaminase toxicity.PMIDSafety and tolerability of lurbinectedin (PM01183) in patients with acute myeloid leukemia and myelodysplastic syndrome.Benton CB et al. · Hematol Oncol 2018 · PMID 30153704Phase 1 with grade 4 rhabdomyolysis as a dose-limiting toxicity and creatinine rise — earliest muscle/renal signal.PMIDUnveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.Calles A et al. · Mol Cancer Ther 2025 · PMID 39636909Mechanism review (oncogenic transcription inhibition and RNA Pol II degradation).PMIDTreatment of Small Cell Lung Cancer with Lurbinectedin: A Review.Rajput PS et al. · Anticancer Agents Med Chem 2022 · PMID 34229593Comprehensive drug review covering the 2020 approval and safety profile.