What are high and low risk chemotherapy regimens for neutropenia?

High and Low Risk Chemotherapy Regimens for Neutropenia

Chemotherapy regimens with a risk of febrile neutropenia >20% are considered high-risk, while those with 10-20% risk are intermediate-risk, and those with <10% risk are low-risk. 1

High-Risk Regimens (>20% risk of febrile neutropenia)

Hematologic Malignancies:

• ALL induction regimens 1
• Non-Hodgkin's Lymphomas:
  • CFAR (cyclophosphamide, fludarabine, alemtuzumab, rituximab) for CLL with del(17p) 1
  • ICE (ifosfamide, carboplatin, etoposide) for DLBCL and PTCLs 1
  • RICE (rituximab, ifosfamide, carboplatin, etoposide) 1
  • CHOP-14 ± rituximab 1
  • MINE (mesna, ifosfamide, novantrone, etoposide) 1
  • DHAP (dexamethasone, cisplatin, cytarabine) 1
  • ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine) 1
  • HyperCVAD + rituximab 1

Solid Tumors:

• Breast Cancer:
  • Docetaxel + trastuzumab (metastatic or relapsed) 1
  • Dose-dense AC followed by T (doxorubicin, cyclophosphamide, paclitaxel) 1
  • TAC (docetaxel, doxorubicin, cyclophosphamide) 1
• Bladder Cancer:
  • MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) 1
• Melanoma:
  • Dacarbazine-based combinations 1
• Pancreatic Cancer:
  • FOLFIRINOX 1
• Gastric Cancer:
  • DCF (docetaxel, cisplatin, fluorouracil) 1

Intermediate-Risk Regimens (10-20% risk of febrile neutropenia)

• Breast Cancer:
  • Docetaxel every 21 days 1
  • CMF classic (cyclophosphamide, methotrexate, fluorouracil) 1
  • AC (doxorubicin, cyclophosphamide) + sequential docetaxel (taxane portion only) 1
  • FEC (fluorouracil, epirubicin, cyclophosphamide) + sequential docetaxel 1
  • Paclitaxel every 21 days (metastatic or relapsed) 1
• Colorectal Cancer:
  • FOLFOX (fluorouracil, leucovorin, oxaliplatin) 1
• Non-Hodgkin's Lymphomas:
  • EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) for AIDS-related NHL 1

Patient Risk Factors That Increase Neutropenia Risk

When evaluating a patient's overall risk for febrile neutropenia, these additional factors should be considered, especially for intermediate-risk regimens 1, 2:

• Age ≥65 years 1, 2
• Previous chemotherapy or radiation therapy 1
• Preexisting neutropenia or bone marrow involvement with tumor 1
• Poor performance status 1
• Poor renal function 1
• Liver dysfunction, especially elevated bilirubin 1
• Recent surgery 1
• Infection/open wounds 1
• Advanced disease stage 3

Clinical Decision-Making Algorithm

1. Assess chemotherapy regimen risk:

   • High-risk (>20%): Recommend primary prophylaxis with G-CSF 1, 2
   • Intermediate-risk (10-20%): Evaluate patient risk factors 1, 2
   • Low-risk (<10%): G-CSF prophylaxis not routinely recommended 2

2. For intermediate-risk regimens:

   • If patient has ≥1 risk factors: Consider G-CSF prophylaxis 1, 2
   • If no risk factors: G-CSF not indicated for primary prophylaxis 2

3. G-CSF administration guidelines:

   • Start 24-72 hours after completion of chemotherapy 4, 2
   • Never administer on same day as chemotherapy 4, 2
   • For daily G-CSFs (filgrastim, tbo-filgrastim): Continue until post-nadir ANC recovery 4, 2
   • For long-acting G-CSFs (pegfilgrastim): Single 6 mg dose per cycle 2

Important Considerations and Pitfalls

• G-CSF should be avoided during concurrent chemoradiotherapy to the chest due to increased risk of complications and death 1, 2
• Certain drug combinations can increase neutropenia risk, such as cyclophosphamide with protease inhibitors 5
• Paclitaxel administered after cisplatin increases myelosuppression compared to the reverse sequence 6
• Dose reductions and treatment delays should be considered for patients who develop febrile neutropenia despite G-CSF prophylaxis 1, 7
• Advanced disease stage is an independent risk factor for severe neutropenia, particularly in breast cancer patients 3
• Bone pain is a common side effect of G-CSF that can be managed with NSAIDs 2