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Vinca alkaloid

Vinflunine

Javlor · VFL

Vinca alkaloid · approved 2009 · 5 references

A fluorinated vinca alkaloid used precisely because patients are too renally impaired for cisplatin — its renal story is careful dose-banding, not direct kidney injury.

Signature injury
Electrolyte Disturbance
Severity
Mild
Reversibility
Reversible
Onset
Electrolyte/prerenal effects can appear within days of a cycle; PK accumulation in renal impairment is immediate but mitigated by protocol dose reduction.

Signature kidney injury & incidence

Electrolyte Disturbance — representative grade ≥3 incidence ~12%.

No strong direct nephrotoxic signal. Vinflunine is given to renally impaired, cisplatin-unfit patients with a defined dose-reduction schema, and tolerability in renal impairment mirrors that of patients with normal renal function once dose-banded. SIADH/hyponatremia is a class-level vinca-alkaloid effect rather than a quantified vinflunine-specific rate. Reported rate: grade >=3 hyponatremia in 12% — 51 patients with relapse-sensitive or relapse-refractory small cell lung cancer treated with single-agent vinflunine… (Spigel 2010, PMID 20521355).

Source: Spigel et al., J Thorac Oncol 2010

Reported injury signatures: Electrolyte Disturbance, Prerenal / Hemodynamic AKI, SIADH / Hyponatremia.

Renal toxicity profile

  1. Electrolyte DisturbancePrimary~12%Grade 3/4 hyponatremia in 12% on single-agent vinflunine 320 mg/m2 (relapsed SCLC phase II)
  2. SIADH / HyponatremiaSecondary
  3. Prerenal / Hemodynamic AKIRare

Onset timing & rechallenge

Acute (~1–7 days) — Electrolyte/prerenal effects within days of a cycle.

Mechanism of kidney injury

Vinflunine is not a recognized direct tubular toxin. The renal-relevant mechanism is pharmacokinetic: renal dysfunction modestly reduces vinflunine clearance (about a 12% decrease at CrCl 40-60 mL/min and ~28% at 20-40 mL/min), so dose banding restores comparable exposure. As a vinca alkaloid, it can be associated with SIADH (euvolemic hyponatremia) at the class level; prerenal physiology may arise from gastrointestinal toxicity and reduced intake.

Clinical presentation

Renal involvement is generally limited to electrolyte disturbance (hyponatremia, occasionally consistent with SIADH) and prerenal azotemia from constipation/ileus, nausea and reduced oral intake. Direct AKI from the drug itself is not a characteristic feature.

Management

Largely supportive: correct hyponatremia per cause (fluid restriction for SIADH), restore volume for prerenal states, and manage constipation aggressively. Continue dose-banded therapy unless intolerance arises. No drug-specific renal antidote is needed.

Risk factors

  • Pre-existing renal impairment (the indicated population)
  • Volume depletion from vinca-induced constipation/ileus, nausea, vomiting
  • Concomitant nephrotoxins or diuretics
  • Advanced age and poor performance status

Prevention

  • Apply the validated CrCl-based dose schema (e.g., 280 mg/m2 for CrCl 40-60; 250 mg/m2 for CrCl 20 to <40)
  • Aggressive bowel regimen to prevent ileus-related volume shifts

Renal dose adjustment

Per phase I PK data: 320 mg/m2 for CrCl >60 mL/min; 280 mg/m2 for CrCl 40-60 mL/min (inclusive of both bounds); 250 mg/m2 for CrCl 20 to <40 mL/min. These bands yield exposure comparable to patients with normal renal function.

Dialyzability & ESKD dosing

Not established as dialyzable in routine practice; vinflunine is largely hepatically metabolized (CYP3A4) with a large volume of distribution, making meaningful dialytic removal unlikely. Manage by dose banding, not dialysis timing.

Differential diagnosis

Separate vinca-associated SIADH/hyponatremia and prerenal azotemia (from ileus, poor intake) from intrinsic AKI due to tumor obstruction, contrast, or concomitant nephrotoxins. Vinflunine itself is rarely the direct cause of a structural nephron lesion.

Monitoring

  • Creatinine clearance before dosing to set the correct dose band
  • Serum sodium (SIADH/hyponatremia surveillance)
  • Volume status and bowel function (ileus risk)
  • CBC (neutropenia is the dominant dose-limiting toxicity)

Key trials & series

  • Isambert et al. 2014 — phase I PK/tolerability defining CrCl-based dosing (280 and 250 mg/m2 bands)
  • De Santis et al. 2015 (JASINT1) — vinflunine-gemcitabine vs vinflunine-carboplatin in cisplatin-unfit (CrCl 30-60) urothelial carcinoma
  • Holmsten et al. 2019 (VINGEM) — vinflunine-gemcitabine vs carboplatin-gemcitabine in cisplatin-ineligible patients with renal impairment

Clinical pearls

  • Watch sodium: SIADH is a vinca-class effect.
  • Constipation/ileus can drive prerenal azotemia — keep the bowels moving.

Anticancer mechanism

Vinflunine is a third-generation, bifluorinated vinca alkaloid that binds tubulin and inhibits microtubule dynamics, arresting cells in mitosis (M phase) and triggering apoptosis. It is approved as second-line therapy for advanced/metastatic urothelial (transitional-cell) carcinoma after platinum failure, and is studied in first-line cisplatin-ineligible disease — a population defined largely by renal impairment.

Note

An instructive case where a drug is selected because of renal impairment. The clinical message is correct dose banding and electrolyte vigilance, not avoidance for nephrotoxicity.

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) — 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

5 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.Phase II trial of vinflunine in relapsed small cell lung cancerSpigel DR et al. · Journal of Thoracic Oncology · 2010 · PMID 20521355
  2. 2.A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen.Culine S, Theodore C, De Santis M, et al · Br J Cancer · 2006 · PMID 16622447
  3. 3.How to manage intravenous vinflunine in cancer patients with renal impairment: results of a pharmacokinetic and tolerability phase I study.Isambert N et al. · Br J Clin Pharmacol · 2014 · PMID 24283925
  4. 4.Vinflunine-gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1).De Santis M et al. · Ann Oncol · 2015 · PMID 26673352
  5. 5.Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: A randomised phase II trial (VINGEM).Holmsten K et al. · Eur J Cancer · 2019 · PMID 31648851
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.