Marine alkylating agent
Lurbinectedin
Zepzelca · LURB
Marine alkylating agent · approved 2020 · 7 references
A synthetic ecteinascidin for small-cell lung cancer whose rare renal injury follows rhabdomyolysis or tumor lysis.
- Signature injury
- Acute Tubular Necrosis
- Severity
- Mild
- Reversibility
- Reversible
- Onset
- Variable across cycles (not tightly defined) — monitor with each dose.
Signature kidney injury & incidence
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
Reported injury signatures: Acute Tubular Necrosis, Electrolyte Disturbance, Crystal / Obstructive Nephropathy.
Renal toxicity profile
- Acute Tubular NecrosisPrimary
- Electrolyte DisturbanceSecondary
- Crystal / Obstructive NephropathySecondary
Onset timing & rechallenge
Variable / unpredictable — Onset varies across cycles and is not tightly defined, warranting monitoring with each dose.
Mechanism of kidney injury
Clinical presentation
Management
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
- Hydration; G-CSF prophylaxis for neutropenia
- Avoid extravasation (vesicant — prefer a secure/central line)
- Tumor-lysis prophylaxis in high-burden disease
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
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
- CK and renal function at baseline and periodically
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.
Anticancer mechanism
Note
Guidelines & consensus
Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.
- ADQI (2026) — Conventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupCisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.Kidney Int · PMID 41881107
- ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
- SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
- ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
- ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
- ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
- KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
- KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
- KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525
References
7 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Lurbinectedin 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 32224306
- 2.Combination 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 36252599
- 3.U.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 36151005
- 4.Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours.Leary A et al. · Eur J Cancer · 2023 · PMID 37634282
- 5.Safety and tolerability of lurbinectedin (PM01183) in patients with acute myeloid leukemia and myelodysplastic syndrome.Benton CB et al. · Hematol Oncol · 2018 · PMID 30153704
- 6.Unveiling 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 39636909
- 7.Treatment of Small Cell Lung Cancer with Lurbinectedin: A Review.Rajput PS et al. · Anticancer Agents Med Chem · 2022 · PMID 34229593
Case reports & series (1)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[C · Limited]Lurbinectedin-Induced Tumor Lysis Syndrome in Small Cell Neuroendocrine Cancer of the Cecum: A First-Ever Case Report.Wahab A et al. · Am J Case Rep · 2021 · PMID 34125741