What is the preferred anticoagulation regimen for a patient with metastatic non-small cell lung cancer (NSCLC) and segmental pulmonary embolism, considering a history of non-adherence to complicated treatment regimens, based on National Comprehensive Cancer Network (NCCN) guidelines?

Preferred Anticoagulation Regimen for Cancer-Associated Pulmonary Embolism

Enoxaparin 80 mg (1 mg/kg) subcutaneously twice daily is the preferred anticoagulation regimen for treating RM's venous thromboembolism based on NCCN guidelines. 1

Rationale for LMWH Selection

The NCCN Guidelines clearly recommend low molecular weight heparin (LMWH) as the preferred treatment for cancer-associated venous thromboembolism (VTE), particularly for the first 6 months in patients with proximal DVT or pulmonary embolism and for prevention of recurrent VTE in patients with advanced metastatic cancer. 1

For this 57-year-old female with:

• Newly diagnosed metastatic non-small cell lung cancer
• Segmental pulmonary embolism
• History of non-adherence to complicated regimens
• Normal renal function (creatinine 0.7 mg/dL)
• Weight of 75 kg

The specific recommended regimen is enoxaparin 1 mg/kg subcutaneously twice daily, which calculates to 75 mg (rounded to 80 mg) twice daily. 1

Comparison with Other Options

1. Dabigatran 150 mg orally twice daily:

   • Not appropriate as first-line therapy for cancer-associated VTE
   • Requires 5-10 days of parenteral anticoagulation before initiation 2
   • Only recommended for patients who refuse or have compelling reasons to avoid LMWH 1

2. Apixaban 10 mg orally twice daily for 7 days, then 5 mg twice daily:

   • While listed as an option in the NCCN guidelines, it's only recommended for patients who refuse or have compelling reasons to avoid LMWH 1
   • Given the patient's history of non-adherence, the more established cancer-specific therapy (LMWH) is preferred

3. Warfarin 5 mg orally daily titrated to INR 2-3:

   • Inferior to LMWH for cancer-associated VTE 1
   • Requires frequent monitoring and dose adjustments
   • Particularly problematic for a patient with known adherence issues

Evidence Supporting LMWH

The preference for LMWH in cancer-associated VTE is based on high-quality evidence:

• Multiple randomized controlled trials have demonstrated superior efficacy of LMWH over vitamin K antagonists in cancer patients 1
• Dalteparin has FDA approval specifically for cancer-associated thrombosis, but enoxaparin has also been extensively studied and is recommended by NCCN 1
• The CLOT trial showed significantly reduced recurrent VTE with LMWH compared to warfarin in cancer patients 1

Considerations for Patient Adherence

Given RM's history of non-adherence to complicated treatment regimens:

• While twice-daily injections may seem challenging, the regimen is straightforward with fixed dosing based on weight
• DOACs like apixaban or dabigatran might seem more convenient (oral administration), but:
  1. They're not first-line therapy for cancer-associated VTE per NCCN guidelines
  2. The efficacy data is not as robust as for LMWH in cancer patients
  3. Dabigatran requires initial parenteral anticoagulation, adding complexity

Duration of Therapy

NCCN Guidelines recommend:

• Minimum duration of 3 months
• For cancer-associated VTE, indefinite anticoagulation while cancer is active, under treatment, or if risk factors for recurrence persist 1

Important Monitoring Considerations

• Baseline laboratory testing: CBC, renal and hepatic function panel, aPTT, and PT/INR
• Following initiation: Hemoglobin, hematocrit, and platelet count at least every 2-3 days for the first 14 days and every 2 weeks thereafter 1
• Regular assessment of bleeding risk and renal function

Pitfalls to Avoid

1. Underdosing: Full therapeutic dosing is required despite cancer bleeding risk
2. Inappropriate DOAC use: While convenient, DOACs are not first-line for cancer-associated VTE
3. Inadequate duration: Treatment should continue while cancer is active
4. Failing to reassess: Periodically reassessing the risk-benefit ratio of anticoagulation is essential 3

In conclusion, enoxaparin 80 mg (1 mg/kg) subcutaneously twice daily represents the optimal choice for this patient with metastatic NSCLC and pulmonary embolism, balancing efficacy, safety, and the patient's clinical characteristics according to NCCN guidelines.