Can carboplatin (Carboplatin) and paclitaxel (Paclitaxel) cause acute fever and neutrophil predominance?

Carboplatin and Paclitaxel Can Cause Acute Fever with Neutropenia, Not Neutrophil Predominance

Yes, carboplatin and paclitaxel combination chemotherapy commonly causes acute fever associated with severe neutropenia (low neutrophil counts), not neutrophil predominance. This is a critical distinction—these agents cause neutrophil depletion, not elevation.

Hematologic Toxicity Profile

Neutropenia as the Primary Toxicity

• Bone marrow suppression with severe neutropenia is the dose-limiting toxicity of paclitaxel, with neutrophil counts frequently declining below 500 cells/mm³ 1
• Carboplatin causes dose-dependent myelosuppression, with thrombocytopenia occurring in 25% of patients (platelet counts <50,000/mm³) and neutropenia with granulocyte counts below 1,000/mm³ in 16% of patients 2
• When combined, the regimen produces Grade IV neutropenia in 74-81% of patients, depending on the specific dosing schedule 1

Febrile Neutropenia Incidence

• The incidence of neutropenic fever with gemcitabine/cisplatin/paclitaxel was substantially higher (13.2%) compared to gemcitabine/cisplatin alone (4.3%; P<0.001) in bladder cancer trials 3
• In lung cancer patients receiving carboplatin/paclitaxel, fever was frequent (12% of all treatment courses), with infectious episodes occurring in 30% of patients 1
• Febrile neutropenia occurred in 15% of ovarian cancer patients receiving paclitaxel plus cisplatin versus 4% with cyclophosphamide plus cisplatin 1

Clinical Presentation

Fever with Neutropenia, Not Neutrophilia

• Patients develop fever during the neutropenic nadir (typically around day 21), when neutrophil counts are at their lowest 2
• The fever represents infectious complications occurring in the setting of severe immunosuppression, not an inflammatory response with elevated neutrophils 1
• Infectious episodes were fatal in 1% of patients, including sepsis, pneumonia, and peritonitis 1

Recovery Pattern

• By day 28,90% of patients have platelet counts above 100,000/mm³ and 74% have neutrophil counts above 2,000/mm³, indicating the reversible nature of myelosuppression 2
• The NCCN recommends holding chemotherapy until adequate recovery: ANC ≥1,000-1,500/mm³ 4

Important Clinical Caveats

Risk Factors for Severe Toxicity

• Patients with impaired kidney function experience more severe marrow suppression with carboplatin 2
• Poor performance status patients have higher incidence of severe leukopenia and thrombocytopenia 2
• Elderly patients (≥65 years) and those previously treated with cisplatin have increased risk (10%) for peripheral neuropathies 1

G-CSF Considerations

• G-CSF support is recommended for patients who have experienced severe neutropenia to reduce duration and severity in subsequent cycles 1, 4
• In lung cancer studies, granulocytopenia decreased from 70% after the first cycle to 37% during the second cycle and 20% or lower during subsequent cycles with G-CSF support 5
• However, prophylactic G-CSF injections were not effective in preventing febrile neutropenia incidence in ovarian cancer patients receiving paclitaxel/carboplatin in one retrospective study 6

Distinguishing from True Neutrophilia

If a patient presents with fever AND elevated neutrophil counts while on carboplatin/paclitaxel, consider alternative diagnoses such as:

• Post-COVID-19 organizing pneumonia, which can be aggravated by immune checkpoint inhibitors and G-CSF, presenting with high fever and severe hypoxemia 7
• Infection with appropriate bone marrow response (if not profoundly neutropenic)
• Concurrent corticosteroid use causing demargination of neutrophils