Carbotor

Approved Indications:

• Ovarian Cancer
• Initial treatment of advanced ovarian carcinoma in combination with other chemotherapeutic agents (e.g., paclitaxel).
• Palliative treatment of recurrent ovarian cancer as a single agent.
• Non-Small Cell Lung Cancer (NSCLC)
• First-line treatment in combination with paclitaxel or other agents for advanced or metastatic disease.
• Small Cell Lung Cancer (SCLC)
• Alternative to cisplatin in combination regimens for extensive-stage disease.
• Head and Neck Cancers
• Used in combination chemoradiotherapy for squamous cell carcinomas of the head and neck.
• Bladder Cancer
• As part of combination regimens in advanced or metastatic urothelial carcinoma.
• Germ Cell Tumors
• Second-line treatment for metastatic testicular cancer in patients intolerant to cisplatin.
• Endometrial Cancer
• As part of combination regimens for recurrent or metastatic endometrial carcinoma.

Off-label / Clinically Accepted Uses:

• Cervical Cancer
• Concurrent chemoradiation in locally advanced disease.
• Esophageal and Gastric Cancers
• In combination regimens for unresectable or metastatic cases.

Administration Route: Intravenous (IV) infusion only.

Adults (Normal Renal Function):

• Single-agent therapy:
• 360 mg/m² IV over 15–60 minutes on Day 1 every 4 weeks.
• Combination therapy (e.g., with paclitaxel):
• AUC 5–6 (Calvert formula) IV on Day 1 every 3 weeks.

Calvert Formula for Dosing Based on Renal Function:
 Total Dose (mg) = Target AUC × (GFR + 25)
 - GFR: Glomerular Filtration Rate in mL/min
 - AUC target: 4–7 mg/mL·min depending on regimen

Pediatric Use:

• Limited data; specialist consultation required. Dosing individualized by body surface area and renal function.

Elderly:

• Dose adjustment recommended due to reduced renal function. Start at lower AUC targets and monitor closely.

Renal Impairment:

• Use Calvert formula to adjust dose.
• Not recommended in severe renal impairment (GFR <20 mL/min).

Hepatic Impairment:

• No specific adjustment required, but monitor liver function periodically.

Administration Notes:

• Infuse over 15–60 minutes.
• Adequate hydration before and after infusion is recommended.
• Do not use aluminum-containing needles or IV sets.

Carboplatin is a platinum-based cytotoxic agent that forms covalent bonds with DNA, creating intra- and inter-strand DNA cross-links. These platinum-DNA adducts inhibit DNA replication and transcription, ultimately leading to apoptosis. Carboplatin is less reactive than cisplatin but achieves similar cytotoxic activity with reduced nephrotoxicity and gastrointestinal side effects, primarily affecting rapidly dividing cancer cells.

• Absorption: Not applicable (IV only).
• Distribution: Wide distribution in body fluids; moderate plasma protein binding (~30%).
• Metabolism: Undergoes non-enzymatic hydrolysis to reactive platinum species; not metabolized by hepatic enzymes.
• Onset of Action: Within hours; clinical effect depends on cancer type.
• Bioavailability: 100% (IV).
• Half-life:
• Initial: ~1.5 hours
• Terminal: ~6 hours
• Elimination:
• Primarily renal (over 70% excreted unchanged in urine within 24 hours).
• Clearance directly correlates with GFR.

• Pregnancy:
• FDA Pregnancy Category D (based on earlier classification).
• Known to cause fetal harm. Use is contraindicated during pregnancy unless clearly needed.
• Lactation:
• Carboplatin is excreted in breast milk.
• Breastfeeding is not recommended during and for at least 2 weeks after treatment due to potential toxicity to the infant.
• Caution: Women of childbearing potential should use effective contraception during and for 6 months after treatment.

• Primary Class: Antineoplastic Agent
• Subclass: Alkylating Agent (Platinum analog)
• Generation: Second-generation platinum compound (less toxic than cisplatin)

• Known hypersensitivity to carboplatin, other platinum-containing compounds, or formulation excipients
• Severe bone marrow suppression (especially if preexisting)
• Significant bleeding disorders
• Severe renal impairment without ability to adjust dose or monitor closely
• Concurrent use with live vaccines (risk of severe infection)

• Myelosuppression:
• Dose-limiting toxicity. Monitor CBC weekly. Delay next cycle if neutrophils <2,000/mm³ or platelets <100,000/mm³.
• Nephrotoxicity:
• Less than cisplatin but still monitor serum creatinine and electrolytes before each cycle.
• Neurotoxicity:
• Peripheral neuropathy may occur, especially with cumulative doses.
• Ototoxicity:
• Tinnitus and hearing loss (more frequent in children).
• Hypersensitivity reactions:
• May occur after multiple doses (especially after 6 cycles). Monitor for anaphylaxis.
• Infection risk:
• Due to immunosuppression. Monitor for signs of infection.
• Use with Radiation:
• Increases risk of toxicity to bone marrow and gastrointestinal mucosa.

Hematologic:

• Thrombocytopenia
• Neutropenia
• Anemia

Gastrointestinal:

• Nausea, vomiting
• Diarrhea, constipation
• Stomatitis

Neurologic:

• Peripheral neuropathy
• Headache
• Hearing loss (ototoxicity)

Renal:

• Increased serum creatinine
• Electrolyte disturbances (e.g., hypomagnesemia, hypokalemia)

Hypersensitivity:

• Rash
• Urticaria
• Anaphylaxis (rare)

Other:

• Elevated liver enzymes
• Alopecia
• Fatigue

• Nephrotoxic agents (e.g., aminoglycosides, amphotericin B):
• Increased risk of renal toxicity.
• Loop diuretics:
• Enhanced ototoxicity when used concurrently.
• Live vaccines (e.g., yellow fever):
• Avoid due to immunosuppression risk.
• Myelosuppressive drugs (e.g., other chemotherapies):
• Additive bone marrow suppression.
• Aluminum-containing IV sets:
• Carboplatin reacts with aluminum; use non-aluminum equipment.
• CYP450 interactions:
• Not significant; carboplatin does not rely on hepatic metabolism.

• Evolving role in immunochemotherapy regimens:
• Used alongside checkpoint inhibitors (e.g., atezolizumab) in NSCLC and other cancers.
• Renal dosing guidance refined:
• Stronger emphasis on using Calvert formula to avoid toxicity.
• Hypersensitivity surveillance enhanced:
• Desensitization protocols are now recommended for patients with delayed-onset allergic reactions.
• Guidelines (NCCN, ESMO):
• Continued support for carboplatin as preferred alternative to cisplatin in patients with renal impairment or poor tolerance.

• Temperature: Store at 20°C to 25°C (68°F to 77°F).
• Permitted excursions: 15°C to 30°C.
• Light Protection: Protect from light; store in original outer carton.
• Do not freeze.
• Reconstituted solution:
• Use within 8 hours if stored at room temperature.
• May be diluted in D5W or NS for infusion.
• Handling:
• Cytotoxic agent – handle using gloves, gown, and appropriate precautions.