What are the potential side effects of carboplatin in a patient with a history of cancer and recent chemotherapy treatment with taxanes, who also has a history of peripheral neuropathy?

Carboplatin Side Effects

Carboplatin's dose-limiting toxicity is bone marrow suppression, particularly thrombocytopenia, which occurs in 25-35% of patients, with the nadir typically occurring around day 21. 1

Critical Context for Patients with Pre-existing Peripheral Neuropathy

In patients with a history of taxane-induced peripheral neuropathy, carboplatin is significantly less neurotoxic than cisplatin and produces fewer neurologic side effects. 1 Importantly, in 70% of patients with pre-existing cisplatin-induced peripheral neurotoxicity, there was no worsening of symptoms during carboplatin therapy 1. However, patients older than 65 years and/or previously treated with cisplatin have an increased risk (10%) for peripheral neuropathies with carboplatin 1.

Hematologic Toxicity (Dose-Limiting)

• Thrombocytopenia (platelet count <50,000/mm³) occurs in 25% of patients overall and 35% in pretreated ovarian cancer patients 1
• Neutropenia (granulocyte count <1,000/mm³) occurs in 16% of patients overall and 21% in pretreated patients 1
• Leukopenia (WBC <2,000/mm³) occurs in 15% of patients overall and 26% in pretreated patients 1
• Anemia (hemoglobin <11 g/dL) occurs in 71-90% of patients, with severe anemia (<8 g/dL) in 14-21% 1
• The nadir typically occurs around day 21, with recovery by day 28 in most patients (90% have platelets >100,000/mm³) 1
• Marrow suppression is more severe in patients with impaired kidney function or poor performance status 1
• Transfusions are required in 26-44% of patients 1
• Infectious or hemorrhagic complications occur in 5% of patients, with drug-related death in <1% 1

Gastrointestinal Toxicity

• Vomiting occurs in 65-81% of patients, with severe vomiting in approximately one-third 1
• Nausea occurs in an additional 10-15% of patients 1
• Carboplatin is significantly less emetogenic than cisplatin, though patients previously treated with emetogenic agents (especially cisplatin) are more prone to vomiting 1
• Nausea and vomiting usually cease within 24 hours and are responsive to antiemetic measures 1
• Other gastrointestinal effects include pain (17%), diarrhea (6%), and constipation (6%) 1

Neurologic Toxicity (Critical for Your Patient)

Peripheral neuropathies occur in only 4-6% of patients receiving carboplatin, with mild paresthesias being most common. 1 This is significantly lower than cisplatin 1.

• Carboplatin produces significantly fewer and less severe neurologic side effects than cisplatin 1
• Patients >65 years or previously treated with cisplatin have increased risk (10%) for peripheral neuropathies 1
• In 70% of patients with pre-existing cisplatin-induced peripheral neurotoxicity, symptoms did not worsen during carboplatin therapy 1
• Clinical ototoxicity and other sensory abnormalities (visual disturbances, taste changes) occur in only 1% of patients 1
• Central nervous system symptoms occur in 5% of patients, most often related to antiemetic use 1
• Although overall incidence is low, prolonged treatment, particularly in cisplatin-pretreated patients, may result in cumulative neurotoxicity 1

Nephrotoxicity

• Abnormal renal function is uncommon with carboplatin, unlike cisplatin 1
• Serum creatinine elevations occur in 6-10% of patients 1
• Blood urea nitrogen elevations occur in 14-22% of patients 1
• Most abnormalities are mild and reversible in approximately 50% of cases 1
• 27% of patients with baseline creatinine clearance ≥60 mL/min demonstrate reduction below this value during therapy 1

Hepatic Toxicity

• Total bilirubin elevations occur in 5% of patients 1
• SGOT elevations occur in 15-20% of patients 1
• Alkaline phosphatase elevations occur in 24-37% of patients 1
• These abnormalities are generally mild and reversible in approximately 50% of cases 1

Electrolyte Abnormalities

• Magnesium depletion is most common (29-43% of patients) 1
• Sodium depletion occurs in 10-47% of patients 1
• Potassium depletion occurs in 16-28% of patients 1
• Calcium depletion occurs in 16-31% of patients 1
• These abnormalities are rarely symptomatic 1

Allergic Reactions

• Hypersensitivity reactions occur in 2-11% of patients 1
• Reactions include rash, urticaria, erythema, pruritus, and rarely bronchospasm and hypotension 1
• Anaphylactic reactions have been reported in postmarketing surveillance 1
• Successfully managed with standard epinephrine, corticosteroid, and antihistamine therapy 1

Other Side Effects

• Pain occurs in 23-44% of patients 1
• Asthenia (weakness) occurs in 11-41% of patients 1
• Alopecia occurs in 2-49% of patients 1
• Cardiovascular events occur in 6-19% of patients 1
• Respiratory effects occur in 6-10% of patients 1
• Mucositis occurs in 1-8% of patients 1
• Injection site reactions (redness, swelling, pain) have been reported, with rare cases of necrosis associated with extravasation 1

Critical Pitfall for Your Patient

When carboplatin is combined with taxanes (as in paclitaxel/carboplatin regimens), neurotoxicity data are confounded because taxanes are among the most neurotoxic drugs. 2 In such combinations, most neuropathy is likely attributable to the taxane component rather than carboplatin 2. Given your patient's history of taxane-induced peripheral neuropathy, carboplatin monotherapy or carboplatin-based regimens without taxanes would be significantly less likely to worsen existing neuropathy compared to continuing taxane therapy 1.