How should kidney function be monitored during Fotemustine therapy?

Serum creatinine / eGFR at baseline and before cycles, with delayed-onset surveillance; Urinalysis for tubular markers; CBC (thrombocytopenia/leukopenia are dominant, often delayed); Running tally of cumulative nitrosourea dose.

How can kidney injury from Fotemustine be prevented?

Cap cumulative nitrosourea dose exposure

Who is at higher risk of kidney injury from Fotemustine?

High cumulative nitrosourea dose; Pre-existing renal impairment; Concurrent nephrotoxins (notably cisplatin in melanoma regimens); Volume depletion from nausea/vomiting.

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Printable monograph

Nitrosourea (alkylating)

Fotemustine

Muphoran · FTM

Nitrosourea (alkylating) · approved 1989 · 4 citations

Dated evidence· through 2015

Fairly sourced4/9 · 3 signals

Not met: 4 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 24y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Not met: Current through 2015
Not met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

A lipophilic nitrosourea for melanoma and glioma whose class carries delayed, cumulative tubulointerstitial kidney injury — usually mild, but occasionally consequential.

ModerateLate-1980s nitrosourea

Disseminated malignant melanoma, including cerebral metastasesRecurrent high-grade glioma / glioblastoma (often after temozolomide)

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Signature kidney injury

Signature lesion

Chronic Interstitial Nephropathy

Renal toxicity is generally reported as mild within fotemustine regimens, but, consistent with the nitrosourea class, delayed tubulointerstitial injury/ATN can occur; in one combination study renal toxicity was mild yet possibly contributed to two deaths. Drug-specific incidence is not well quantified and is often confounded by co-administered cisplatin.Source: Semb et al., Melanoma Res 1998

Onset & rechallenge

Time to injuryDelayed (>6 weeks / cumulative)

Weeks to months and cumulative with repeated cycles; chronic interstitial injury may appear after prolonged exposure.

Distilled from: “Delayed — weeks to months, and cumulative with repeated cycles; chronic interstitial injury may appear after prolonged exposure.”

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Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Chronic Interstitial Nephropathy#1 · Signaturequalitative — no citable incidence
Slow, cumulative tubulointerstitial scarring — fibrosis, tubular atrophy and glomerulosclerosis with no discrete acute phase. The nitrosourea (carmustine/lomustine) lesion and delayed radioligand (radiation) nephropathy; often irreversible and detected only as a creeping creatinine months to years later.
Acute Tubular NecrosisSecondaryqualitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityPartially reversible

Evidence4 citations

Nephron map

Proximal Tubule

Distal Tubule / Collecting Duct

InterstitiumSupporting tissue around the tubules

Chronic Interstitial Nephropathy

Slow, cumulative tubulointerstitial scarring — fibrosis, tubular atrophy and glomerulosclerosis with no discrete acute phase. The nitrosourea (carmustine/lomustine) lesion and delayed radioligand (radiation) nephropathy; often irreversible and detected only as a creeping creatinine months to years later.

§03

Kidney injury

Mechanism of kidney injury

As a chloroethyl-nitrosourea, fotemustine and its reactive metabolites can alkylate and carbamoylate renal tubular and interstitial proteins, producing the class-typical pattern of cumulative, dose-related tubulointerstitial nephritis and tubular (ATN-type) injury seen with other nitrosoureas (e.g., carmustine, lomustine, semustine). Injury is delayed and dose-dependent. Direct mechanistic data specific to fotemustine are limited, so the mechanism above is inferred at the nitrosourea class level.

Clinical presentation

Typically an insidious rise in serum creatinine, sometimes with tubular dysfunction; overt AKI is uncommon at standard exposure. With high cumulative nitrosourea dosing the class can progress to chronic interstitial fibrosis and CKD. In combination regimens, acute renal events are often driven by accompanying cisplatin.

Management

No specific antidote. Hold or discontinue with significant or progressive renal dysfunction, provide supportive care and volume repletion, and manage as drug-induced tubulointerstitial injury. Given the delayed/cumulative nature, monitor renal function beyond the active treatment window.Lesion-level management framework

Risk factors

High cumulative nitrosourea dose
Pre-existing renal impairment
Concurrent nephrotoxins (notably cisplatin in melanoma regimens)
Volume depletion from nausea/vomiting

Prevention

Cap cumulative nitrosourea dose exposure

Anticancer mechanism· how it treats cancer

Fotemustine is a chloroethyl-nitrosourea alkylating agent. Its high lipophilicity allows central-nervous-system penetration; it alkylates and cross-links DNA (chloroethylation at the O6 position of guanine), causing interstrand cross-links and cytotoxicity independent of cell cycle. It is used for disseminated malignant melanoma (including cerebral metastases) and recurrent high-grade glioma.

Note · Single-drug glioma series (e.g., GEINOFOTE; Scoccianti second-line) report predominantly hematologic toxicity with renal function generally preserved; the clearest renal signal arises in cisplatin-containing melanoma combinations, complicating attribution.

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Clinical depth

Renal dose adjustment

Use caution and consider dose reduction or avoidance in significant renal impairment; specific renal dosing thresholds are not well established for fotemustine. Withhold for evolving renal dysfunction and reassess cumulative exposure.

Dialyzability & ESKD dosing

Dialyzability is not well characterized; nitrosoureas are lipophilic and rapidly metabolized, so dialysis is not a relied-upon removal strategy. Manage by dose limitation and monitoring rather than dialysis timing.

Differential diagnosis

Distinguish delayed nitrosourea tubulointerstitial injury from cisplatin ATN/electrolyte wasting in combination regimens, prerenal azotemia, and tumor- or contrast-related causes. The hallmark of nitrosourea nephrotoxicity is its delayed, cumulative, dose-related interstitial pattern.

Monitoring

Serum creatinine / eGFR at baseline and before cycles, with delayed-onset surveillance
Urinalysis for tubular markers
CBC (thrombocytopenia/leukopenia are dominant, often delayed)
Running tally of cumulative nitrosourea dose

Key trials & series

Semb et al. 1998 — FCT (fotemustine, cisplatin, tamoxifen) in metastatic melanoma; renal toxicity generally mild but possibly contributed to two deaths
Scoccianti et al. 2008 — second-line single-agent fotemustine in temozolomide-pretreated glioblastoma (toxicity mainly hematologic)
Perez-Segura et al. 2015 (GEINOFOTE) — fotemustine in recurrent high-grade glioma with poor performance status (renal function part of safety assessment)

Clinical pearls

Nitrosourea kidney injury is characteristically delayed and cumulative — monitor renal function beyond the end of treatment.
In fotemustine melanoma combinations, much of the acute renal signal is really cisplatin.
Renal toxicity is usually mild but is not zero — it possibly contributed to deaths in the FCT regimen.
Glioma monotherapy series show predominantly hematologic, not renal, dose-limiting toxicity.

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the Nitrosourea (alkylating) class.

Ophthalmic

Keratopathy, uveitis, retinopathy

Visual disturbance (crizotinib)

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

CNS effects (lorlatinib)

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References

4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

4 references · 1991–2015 · 1 since 2013

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

Guidelines & consensus· 14

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.

ADQIConventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupKidney Int 2026 · PMID 41881107Cisplatin 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.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides 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.SIRMSIRM-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)Radiol Med 2022 · PMID 35303246Recommends 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.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies 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.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses 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.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides 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.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three 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.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes 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.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate 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.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates 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.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages 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.

Where Fotemustine sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Nimustine (ACNU)

Nidran · Nitrosourea (alkylating)

Profile

Water-soluble nitrosourea; renal risk inferred at class level; cumulative delayed tubulointerstitial injury; DLT is myelosuppression.

CINATNLYTE

Moderate#1 · 99% phenotype match

Pemetrexed

Alimta · Antifolate

Profile

Cumulative chronic tubulointerstitial injury; RTA and nephrogenic DI.

CINATNLYTE

Moderate#2 · 77% phenotype match

Vemurafenib

Zelboraf · BRAF inhibitor

Profile

Strongest renal offender of the BRAF/MEK class: proximal tubular injury/Fanconi and early AKI.

ATNFANCLYTE

Moderate#3 · 75% phenotype match

Lutetium-177 PSMA-617 (vipivotide)

Pluvicto · Radioligand therapy (PSMA)

Profile

PSMA-targeted radioligand for prostate cancer; renal radiation exposure and xerostomia.

CINLYTE

Moderate#4 · 70% phenotype match

Melphalan flufenamide (melflufen)

Pepaxto · Peptide-conjugated alkylator

Profile

Delivers melphalan intracellularly; BRIDGE supports a reduced 30 mg dose in moderate renal impairment.

ATNLYTE

Moderate#5 · 70% phenotype match

Trabectedin

Yondelis · Marine alkylating agent

Profile

Rhabdomyolysis → pigment nephropathy; hepatotoxicity.

ATNLYTE

Moderate#6 · 66% phenotype match

Compare Fotemustine with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across Alkylating agents

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.