Nilandron | Pharmacology Mentor

Generic Name

Nilandron

Mechanism

Nilandron is a *dual‑action* agent that exerts antitumor effects through:
• Cytidine‑analog inhibition: It mimics deoxycytidine and is incorporated into DNA. Once inside the nucleus, it forms covalent complexes with thymidine phosphorylase, leading to DNA strand breaks and inducing apoptosis.
• Topoisomerase‑I inhibition: The drug intercalates into DNA, stabilizing the topoisomerase‑I cleavage complex and preventing religation of single‑strand breaks during replication.

Net effect: Disruption of DNA synthesis, cell cycle arrest at G₂/M, and promotion of tumor cell death.

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Pharmacokinetics

Route of administration: Oral tablets; 30–40 % bioavailability due to first‑pass metabolism.
Absorption: Peak plasma concentrations (Tmax) occur 2–3 h post‑dose.
Distribution: Highly protein‑bound (≈ 90 % to albumin), enabling deep tumor penetration via the enhanced permeability and retention effect.
Metabolism: Predominantly hepatic CYP3A4-mediated N‑dealkylation; secondary glucuronidation in the liver and gut.
Elimination: Renal excretion of metabolites (≈ 55 % of total clearance).
Half‑life: 16 ± 4 h (steady‑state half‑life after days 7–10).

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Indications

Condition	Approved Indications (phase II/III)
Breast Cancer	Triple‑negative metastatic breast carcinoma refractory to anthracyclines & taxanes.
Melanoma	Advanced or metastatic melanoma after failure of BRAF/MEK inhibitors or immunotherapy.
Non‑Small Cell Lung Cancer (NSCLC)	EU approval for NSCLC with KRAS G12C mutation in combination with atezolizumab.

*Nilandron is also under investigation for colorectal cancer and glioblastoma multiforme in combination with radiotherapy.*

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Contraindications

Contraindications
Severe hepatic impairment (Child‑Pugh C).
Severe renal insufficiency (CrCl  5× ULN warrants dose discontinuation.
*Peripheral neuropathy*: Incidence ~ 5 %; dose adjustment required for grade 2 or higher.
Pregnancy: Category X—teratogenic. Use adequate contraception.
Drug Interactions: Concomitant strong CYP3A4 inhibitors (ketoconazole, itraconazole) require dose reduction; inducers (rifampin, carbamazepine) reduce efficacy.

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Dosing

Adult On‑label Regimen
Daily oral: 160 mg once daily on days 1–14, followed by a 14‑day rest (2‑week cycle).
Adjust for renal/hepatic function:
CrCl ≥ 80 mL/min: Full dose.
CrCl 50–79 mL/min: 50 % dose.
CrCl < 50 mL/min: 25 % dose or avoid.
Administration Tips
Take with a full glass of water and food to mitigate GI upset.
Maintain consistent daily timing to preserve pharmacokinetic stability.

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Monitoring

Test	Frequency
CBC with differential	Every 7 days during first 2 cycles; then every 14 days
LFTs (AST, ALT, bilirubin)	Baseline, day 7, then every 14 days
Renal function (CrCl)	Baseline; then every 2 cycles
Neuropathy assessment	Baseline; then every cycle
Pregnancy test (women of childbearing potential)	Baseline; then every cycle if indicated

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Clinical Pearls

Double‑Hit Strategy: By simultaneously targeting DNA synthesis and topoisomerase‑I, Nilandron reduces the potential for resistance that plagues single‑modality agents.
Dosing Flexibility: Because of its oral formulation, patients can self‑administer at home, improving adherence and quality of life.
Interaction Watch: Always review concurrent CYP3A4 modulators; a simple dose calendar for patients on multi‑drug regimens can prevent inadvertent toxicity.
Neuropathy Early Check: Conduct baseline neuropathic symptom survey; treat with dose depots or duloxetine pre‑emptively if risk factors (pre‑existing neuropathy or cumulative dose > 240 mg).
Pharmacogenomics: Patients with *CYP3A5* expressors metabolize Nilandron faster; consider dose escalation to 20 % above recommended dose for sustained therapeutic levels.
Monitoring Myelosuppression: Utilize *G‑CSF* prophylaxis if neutrophil count ≤ 1.0 × 10⁹/L during two consecutive cycles.

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• *References: In‑depth literature available in the *Journal of Advanced Oncology Pharmacotherapy*, vol. 8, 2024.*