What is the cause of drowsiness in a lung cancer patient after one cycle of chemotherapy with nab-paclitaxel (paclitaxel), carboplatin, and pembrolizumab (anti-PD-1 monoclonal antibody)?

Drowsiness After First Cycle of Nab-Paclitaxel, Carboplatin, and Pembrolizumab in Lung Cancer

Drowsiness in this patient is most likely multifactorial, stemming from chemotherapy-induced anemia, direct neurotoxic effects of carboplatin and nab-paclitaxel, and potentially immune-related neurologic adverse events from pembrolizumab.

Primary Causes to Evaluate

Chemotherapy-Induced Hematologic Toxicity

Anemia is a leading cause of fatigue and drowsiness after this regimen and should be assessed immediately with complete blood count.

• Carboplatin causes significant anemia, with grade 3/4 anemia occurring in 18-20% of patients receiving platinum-based doublets 1
• The nab-paclitaxel/carboplatin combination specifically causes anemia in 86% of patients (8% severe) 2
• Anemia below 11 g/dL occurs in 78-90% of patients receiving paclitaxel-platinum combinations, with severe anemia (<8 g/dL) in 10-12% 2

Direct Neurotoxic Effects

Peripheral neuropathy from both carboplatin and nab-paclitaxel can manifest as generalized fatigue and drowsiness, not just sensory symptoms.

• Carboplatin causes more neurotoxicity than cisplatin in platinum-based regimens 1
• Paclitaxel causes peripheral neuropathy in 60% of patients overall, with symptoms including hyperesthesia that can contribute to fatigue 2
• Neurologic symptoms appear early, with 27% experiencing them after the first course 2
• The combination of paclitaxel with platinum agents results in neurosensory toxicity in 48-61% of patients, with severe symptoms in 13-28% 2

Immune-Related Neurologic Adverse Events

Pembrolizumab can cause immune-mediated neurologic toxicity including myasthenia-like syndromes that present with fatigue and weakness.

• Lambert-Eaton myasthenic syndrome has been documented as an immune-related adverse event from pembrolizumab, presenting with muscle weakness, fatigue, and drowsiness 3
• Immune-related adverse events of grade 3 or higher occur in 29% of patients receiving pembrolizumab with chemotherapy 4
• Neurologic immune-related adverse events can occur early in treatment, even after one cycle 3

Secondary Contributing Factors

Cardiovascular Effects

• Paclitaxel causes hypotension during infusion in 12% of patients, which can contribute to persistent fatigue 2
• Bradycardia occurs in 3% of patients and may cause drowsiness 2
• Cardiovascular events occur in 12-13% of NSCLC patients receiving paclitaxel-platinum combinations 2

Metabolic and Systemic Effects

• Nausea and vomiting occur in 85% of patients receiving paclitaxel-platinum combinations (27-29% severe), leading to dehydration and electrolyte imbalances that cause drowsiness 2
• Infections occur in 48-69% of patients after platinum-based chemotherapy, with occult infections causing fatigue 2

Immediate Diagnostic Workup

Check the following laboratory studies urgently:

• Complete blood count with differential to assess for anemia (hemoglobin <11 g/dL), neutropenia, and thrombocytopenia 2
• Comprehensive metabolic panel to evaluate for electrolyte disturbances, renal dysfunction, and hepatic toxicity 5
• Thyroid function tests, as pembrolizumab causes immune-mediated thyroid dysfunction that presents with fatigue 4

Perform focused neurologic examination:

• Assess for peripheral neuropathy with sensory testing and deep tendon reflexes 2
• Evaluate for proximal muscle weakness suggesting myasthenia-like syndrome 3
• Check for autonomic dysfunction (orthostatic hypotension, constipation) 2

Management Algorithm

If hemoglobin <10 g/dL: Consider erythropoiesis-stimulating agents or transfusion based on symptoms and comorbidities 1

If peripheral neuropathy is present: Dose reduction of nab-paclitaxel should be considered for subsequent cycles, as nab-paclitaxel was specifically chosen to reduce neurotoxicity risk 1

If immune-related neurologic symptoms suspected: Obtain anti-voltage-gated calcium channel antibodies and consider neurology consultation for electromyography 3

If no clear hematologic or neurologic cause: Evaluate for occult infection, particularly in the setting of neutropenia, and consider imaging if fever or localizing symptoms develop 2

Critical Pitfalls to Avoid

• Do not attribute all drowsiness to "expected chemotherapy side effects" without checking hemoglobin, as severe anemia is common and treatable 2
• Do not miss immune-related neurologic adverse events, which can be life-threatening if not recognized early and may require immunosuppression 3
• Do not overlook medication interactions or polypharmacy, particularly antiemetics and supportive medications that can cause sedation 2
• Do not delay evaluation if drowsiness is accompanied by confusion, severe weakness, or respiratory symptoms, as these may indicate serious complications requiring immediate intervention 2, 3