Cetuximab & Panitumumab
Erbitux · Vectibix · Anti-EGFR antibody
TRPM6 magnesium wasting.
LYTE
MildOpen →
Vinca alkaloid
Vinflunine
Javlor · VFL
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.
Mild2009 (EMA) · approved 2009
Advanced/metastatic urothelial carcinoma after platinum-based therapyFirst-line cisplatin-ineligible urothelial carcinoma (investigational/combination, e.g., with gemcitabine)
Signature kidney injury
Electrolyte Wasting
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.
Source: Isambert et al., Br J Clin Pharmacol 2014
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / Endothelium
Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water
Electrolyte Wasting
Renal loss of magnesium, potassium or calcium — cisplatin and the anti-EGFR antibodies.
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.
Onset
Electrolyte/prerenal effects can appear within days of a cycle; PK accumulation in renal impairment is immediate but mitigated by protocol dose reduction.
Reversibility
Reversible
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.
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 20-40)
- Aggressive bowel regimen to prevent ileus-related volume shifts
- Monitor sodium for SIADH/hyponatremia
- Maintain hydration; avoid stacking nephrotoxins
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.
Clinical depth
Renal dose adjustment
Per phase I PK data: 320 mg/m2 for CrCl >=60 mL/min; 280 mg/m2 for CrCl 40 to <60 mL/min; 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
- Vinflunine is chosen for the renally impaired, cisplatin-unfit urothelial patient — its renal challenge is dosing, not toxicity.
- Renal impairment reduces clearance only modestly (~12-28%), fully managed by the CrCl dose bands.
- Watch sodium: SIADH is a vinca-class effect.
- Constipation/ileus can drive prerenal azotemia — keep the bowels moving.
Where it strikes
Nephron segments
Distal Tubule / Collecting Duct
Fine-tuning of Na, K, Mg, acid & water
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Electrolyte WastingPrerenal / Hemodynamic AKISIADH / Hyponatremia
Beyond the kidney
Class-level context for the major non-renal toxicities of vinca alkaloids.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
Evidence
3 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkHow 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 24283925Defines the CrCl-based dose bands (280 mg/m2 for 40-60 mL/min, 250 mg/m2 for 20-40 mL/min) that normalize exposure in renal impairment.PMIDVinflunine-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 26673352Randomized trial in cisplatin-ineligible patients (CrCl 30-60 mL/min), establishing vinflunine doublets in the renally impaired urothelial population.PMIDVinflunine/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 31648851Phase II trial confirming use of vinflunine in cisplatin-ineligible patients defined by renal impairment (CrCl 30-60 mL/min).