Usage
Carboplatin is primarily used for the treatment of advanced ovarian carcinoma. It is also employed in the treatment of other cancers like lung cancer (small cell and non-small cell), retinoblastoma, testicular cancer, head and neck cancer, endometrial cancer, esophageal cancer, bladder cancer, cervical cancer, and germ cell tumors. Its pharmacological classification is an antineoplastic alkylating agent. Carboplatin acts by binding to DNA and forming intrastrand and interstrand crosslinks, which disrupts DNA replication and ultimately leads to cell death.
Alternate Names
Carboplatin is also known as CARBOplatin Novaplus. Some popular brand names include Paraplatin.
How It Works
Pharmacodynamics: Carboplatin exerts its cytotoxic effects through the formation of various platinum-DNA adducts, predominantly intrastrand crosslinks. These adducts hinder DNA synthesis and function, triggering cell cycle arrest and apoptosis. Similar to cisplatin, carboplatin’s cytotoxicity is cell-cycle non-specific.
Pharmacokinetics:
- Absorption: Administered intravenously, achieving rapid distribution.
- Metabolism: Undergoes slow, non-enzymatic hydrolysis to form active platinum species. The rate of hydrolysis is slower compared to cisplatin.
- Elimination: Primarily excreted renally as unchanged drug with approximately 70% eliminated in the urine within 24 hours. Elimination also occurs through the biliary route to a lesser extent. It exhibits linear pharmacokinetics.
Mode of Action: Carboplatin enters cells primarily through passive diffusion but also through active transport mechanisms. Its cytotoxic effect stems from the formation of platinum-DNA adducts, particularly intrastrand crosslinks involving N7 positions of adjacent guanine and adenine bases. These adducts inhibit DNA replication and function, triggering cell cycle arrest and apoptosis.
Dosage
Standard Dosage
Adults:
The standard carboplatin dosage is based on body surface area (BSA) or calculated using the Calvert formula, which takes into account renal function (glomerular filtration rate - GFR).
- BSA-based dosing: Common regimens include 360 mg/m² intravenously every 4 weeks as a single agent or 300 mg/m² in combination with other chemotherapeutic agents.
- Calvert formula: Dose (mg) = Target AUC x (GFR + 25). This formula allows for individualised dosing based on renal function. A common target AUC is 4-6 mg/mL/min.
Children:
Carboplatin dosing in children is weight-based or determined using BSA. Doses range from 300-600 mg/m² every 4 weeks for solid tumors. For certain malignancies, dosages as high as 560 mg/m² or 18.7 mg/kg may be used. For infants and neonates, dosing is often based on body weight (mg/kg) rather than BSA. Pediatric oncologists often consider additional factors, including the specific malignancy and the patient’s renal function.
Special Cases:
- Elderly Patients: Due to potential age-related decline in renal function, the Calvert formula or a reduced dose is recommended. Close monitoring of renal function and blood counts is crucial.
- Patients with Renal Impairment: Dose adjustment is essential. The Calvert formula is the preferred method to determine dose modifications. The dose is reduced based on the degree of renal impairment.
- Patients with Hepatic Dysfunction: Dose adjustments are generally not necessary, but caution is advised, and close monitoring is warranted.
- Patients with Comorbid Conditions: Carboplatin dosing requires careful consideration in patients with comorbidities like diabetes, cardiovascular disease, and pre-existing hematological disorders.
Clinical Use Cases
Carboplatin’s use in settings like intubation, surgical procedures, mechanical ventilation, and emergency situations is not standard practice. Its primary application is in cancer chemotherapy regimens. The specific dosing and administration depend on the cancer type and treatment protocol.
Dosage Adjustments
Dose adjustments are primarily based on renal function, assessed by GFR. The Calvert formula provides a framework for calculating dose adjustments based on GFR values. Hematologic toxicity also guides dose adjustments. Subsequent doses might be reduced or held based on nadir blood counts (lowest point of white blood cells and platelets) observed after the previous cycle.
Side Effects
Common Side Effects
- Myelosuppression (decreased blood cell counts - neutropenia, thrombocytopenia, anemia)
- Nausea and vomiting
- Fatigue
- Alopecia (hair loss)
- Peripheral neuropathy (numbness and tingling in hands and feet)
- Ototoxicity (hearing loss or tinnitus)
- Elevated liver enzymes
- Renal impairment
- Electrolyte imbalances
Rare but Serious Side Effects
- Anaphylactic reactions
- Hemolytic-uremic syndrome (HUS)
- Secondary malignancies
- Severe allergic reactions
Long-Term Effects
- Peripheral neuropathy
- Ototoxicity
- Renal impairment
- Increased risk of secondary malignancies
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe myelosuppression, anaphylaxis, HUS, and renal failure.
Contraindications
- Hypersensitivity to carboplatin or other platinum-containing compounds
- Severe pre-existing myelosuppression
- Significant bleeding diathesis
Drug Interactions
Carboplatin may interact with nephrotoxic or ototoxic drugs (e.g., aminoglycosides, loop diuretics) potentially increasing the risk of renal impairment and hearing loss. Interactions with other myelosuppressive agents may exacerbate bone marrow suppression. Caution is also advised when combining carboplatin with medications that can affect renal clearance, such as anticonvulsants (phenytoin) and some antibiotics. Live attenuated vaccines are generally avoided during carboplatin treatment.
Pregnancy and Breastfeeding
Carboplatin is contraindicated during pregnancy due to its potential to cause fetal harm. Women of childbearing potential should use effective contraception. Breastfeeding is also contraindicated during carboplatin therapy.
Drug Profile Summary
- Mechanism of Action: Alkylating agent that forms DNA crosslinks, leading to cell death.
- Side Effects: Myelosuppression, nausea, vomiting, fatigue, alopecia, peripheral neuropathy, ototoxicity, renal impairment.
- Contraindications: Hypersensitivity to carboplatin, severe myelosuppression, significant bleeding.
- Drug Interactions: Nephrotoxic and ototoxic agents, myelosuppressive agents.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Based on BSA or Calvert formula, adjusted for renal function and hematological toxicity.
- Monitoring Parameters: Complete blood count (CBC), renal function tests, liver function tests, hearing assessment.
Popular Combinations
Carboplatin is often used in combination with other chemotherapeutic agents, such as cyclophosphamide, paclitaxel, and pemetrexed. The combination is chosen based on the specific type of cancer being treated.
Precautions
- General Precautions: Monitor renal function, liver function, and complete blood counts regularly. Assess for signs of hypersensitivity.
- Specific Populations: Pregnant women (contraindicated), breastfeeding mothers (contraindicated), children and elderly (dose adjustments needed).
- Lifestyle Considerations: Caution advised regarding alcohol consumption during treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Carboplatin?
A: The recommended carboplatin dose is individualized based on the patient’s BSA and renal function. It is often calculated using the Calvert formula: total dose (mg) = Target AUC × (GFR mL/min + 25). BSA-based dosing of 300-360 mg/m² is also common.
Q2: How is Carboplatin administered?
A: Carboplatin is administered intravenously, typically as an infusion over 15-60 minutes.
Q3: What are the most common side effects?
A: Myelosuppression, nausea, vomiting, fatigue, and alopecia are the most common side effects.
Q4: How is Carboplatin dose adjusted for patients with renal impairment?
A: The Calvert formula, which incorporates GFR, guides dose reductions in renal impairment.
Q5: What are the key drug interactions?
A: Nephrotoxic or ototoxic drugs, other myelosuppressive agents, and drugs affecting renal clearance may interact with carboplatin.
Q6: Can Carboplatin be used during pregnancy or breastfeeding?
A: No, carboplatin is contraindicated in both pregnancy and breastfeeding due to the risk of fetal harm.
Q7: What monitoring parameters are crucial during Carboplatin treatment?
A: Close monitoring of complete blood counts, renal function tests, liver function tests, and hearing is important during treatment.
A: The Calvert formula calculates the carboplatin dose (mg) using the desired area under the curve (AUC) and the patient’s GFR: total dose (mg) = Target AUC × (GFR mL/min + 25).
Q9: What is the mechanism of action of Carboplatin?
A: Carboplatin exerts its antitumor activity by binding to DNA and forming crosslinks, disrupting DNA replication and ultimately causing cell death.
Q10: What are the long-term side effects of Carboplatin?
A: Peripheral neuropathy, ototoxicity, renal impairment, and an increased risk of secondary malignancies are potential long-term side effects.
