Myeloid Growth Factors

Tumor

FN-Risk (%)

Regimen

Breast cancer

>20

AC docetaxel, doxorubicin/docetaxel, doxorubicin/paclitaxel, TAC

10–20

AC, EC, docetaxel, FE120C (q4 weeks), CEF

<10

CMF

Colon cancer

10–20

5-FU/folinic acid

FOLFIRI (5-FU/folinic acid/irinotecan)

<10

FOLFOX (5-FU/folinic acid/oxaliplatin)

Hodgkin lymphoma

>20

BEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

Melanoma

>20

Dacarbazine-based combinations

Non-small cell lung cancer

>20

Docetaxel/carboplatin, etoposide/cisplatin

10–20

Paclitaxel/cisplatin, docetaxel/cisplatin, vinorelbine/cisplatin

<10

Paclitaxel/carboplatin, gemcitabine/cisplatin

Non-Hodgkin lymphoma

>20

CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)

DHAP (cisplatin, HD-AraC, dexamethasone)

ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine)

R-CHOP (rituximab-CHOP)

Ovarian carcinoma

>20

Docetaxel, paclitaxel

10–20

Topotecan

<10

Paclitaxel/carboplatin

Small cell lung cancer

>20

ACE, ICE, topotecan

10–20

Etoposid/carboplatin, topotecan/cisplatin

<10

Paclitaxel/carboplatin

EORTC guidelines 2006 [1], ASCO guidelines 2006 [33], and NCCN [8]. Refer to guidelines or original publications for incidences of febrile neutropenia, if other protocols are considered

All figures of febrile neutropenia are derived from the original publications and are related to the dosages of the applied chemotherapy protocols

A doxorubicin, C cyclophosphamide, E etoposide, F 5-fluorouracil, I ifosfamide, M methotrexate, T docetaxel

Besides the type of chemotherapy, there are patient- and tumor-specific factors influencing the risk of febrile neutropenia (Table 18.2).

Table 18.2

Risk factors of febrile neutropenia according National Comprehensive Cancer Network, NCCN 2010) [8] EORTC [1] and ASCO [33]

Chemotherapy-related factors

Type of chemotherapy

Severe neutropenia with previous comparable chemotherapy

>80 % of planned relative dose intensity

Previous neutropenia (<1,000/μl) or lymphocytopenia

Previous extensive chemotherapy

Concomitant or previous radiotherapy with involvement of bone marrow

Therapy with anthracyclines

Mucositis of the whole gastrointestinal tract

Patient risk factors

Age 65 years or older

Female gender

Poor performance status (ECOG ≥2 “Eastern Cooperative Oncology Group”)

Poor nutritional status

Impaired immune function

Tumor risk factors

Cytopenias due to tumor bone marrow involvement

Advanced or uncontrolled tumor

Elevated lactate dehydrogenase (LDH) in lymphoma

Leukemia

Lymphoma

Lung carcinoma

Factors with increased risk for infections

Open wounds

Active infection

Comorbidity

Chronic obstructive lung disease

Cardiovascular disorder

Liver disease (elevated bilirubin, alkaline phosphatase)

Diabetes mellitus

Decreased hemoglobin level at diagnosis

A review of the literature showed that higher age, especially ≥65 years, consistently correlates with a higher risk of febrile neutropenia among the independent patient-specific risk factors [1]. Higher age is an important risk factor as older patients often receive lower or even too low chemotherapy doses in fear of neutropenic complications, although those patients would benefit from an adequate dosed treatment regimen as younger patients [8].

Further independent factors with a high evidence are advanced disease, previous episodes of FN, or missing prophylaxis with G-CSF or antibiotics [1].

Many other patient- or tumor-related factors for FN are known with a lower level of evidence by retrospective analyses such as reduced general condition, impaired nutritional status, or comorbidity.

Patients with malignant diseases of hematopoiesis or lymphopoiesis have an increased risk by the disease itself and the intensity of the treatment than patients with solid tumors.

If patients older than 70 years are analyzed, then it could be shown that age alone is not a risk factor for severe or febrile neutropenia, but the type of malignancy, a planned dose intensity ≥85 %, therapy with cis-platinum or anthracyclines, previous chemotherapy, increased urea, and increased alkaline phosphatase [32].

18.5 Indication for Prophylaxis of Febrile Neutropenia with Myeloid Growth Factors According to Guidelines

Most evidence regarding the clinical effects of myeloid growth factors is derived from studies with G-CSF.

The principle of reducing neutropenia with myeloid growth factors is shown in Fig. 18.1. Neutropenia can be shortened mainly by an accelerated recovery of neutrophils.

Fig. 18.1

Correlation between incidence of infections including febrile neutropenia and neutrophil recovery

The primary prophylaxis with G-CSF halves the incidence of febrile neutropenia (FN) due to chemotherapy with a risk of FN of 40 % [11, 24, 26, 34].

Primary G-CSF prophylaxis to support patients receiving cancer chemotherapy is recommended for all patients judged to be at ≥20 % risk of FN [1, 8, 33].

If using a chemotherapy regimen associated with 10–20 % FN risk, G-CSF prophylaxis should be considered based on treatment intention and individual patient risk factors. The patient’s FN risk should be reassessed prior to each cycle of chemotherapy. This is particularly important for chemotherapy regimens with 10–20 % FN risk, as patient-related risk factors may vary throughout chemotherapy cycles, and thus their FN risk could increase throughout the treatment course.

For patients at <10 % FN risk, routine G-CSF prophylaxis is not recommended.

Figure 18.2 shows the algorithm for deciding to use G-CSF after chemotherapy.

Fig. 18.2

This algorithm is a combined interpretation of the 2006 G-CSF guidelines of European Organisation for Research and Treatment of Cancer (EORTC) and American Society of Clinical Oncology (ASCO) [1, 33]. All of these organizations recommend that the physician should use their clinical judgment to assess FN risk as greater or less than 20 % according to the estimated risk of expected neutropenic complications, based on the treatment regimen and patient-specific characteristics, including age ≥65 years and experience of FN in a previous chemotherapy cycle

Only gold members can continue reading. Log In or Register to continue