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What is the most common dose-limiting toxicity of chemotherapy?



What is Nadir?

The time after chemotherapy at which number of blood cells in the periphery is the lowest


What are the life-threatening consequences of Neutropenia?

Increased risk of infection. Prolonged hospitalization for administration of IV abx. Interruptions in cancer treatment. Increased mortality


What are the patterns of chemotherapy-induced neutropenia?

Rapid: onset within 10-14 days, recover in 3-4 weeks. Delayed: 4-6 weeks, recovery in 6-8 weeks


What is Febrile Neutropenia (FN)?

Absolute neutrophil count (ANC) < 500 cells/mm3 or < 1000 cell/mm3 with a predicted decline to < 500/mm3 within 48 hours. Single temp > 38.2 (101F) or > 37 (100.4) for > 1 hour


What are the symptoms to monitor closely with Neutropenia?

Concerned with infection, watch for: Fever and shaking chills, Dizziness or fainting, Redness or swelling of skin or open wound, Respiratory symptoms (cough or sinus congestion)


When is the risk for Febrile Neutropenia (FN) the greatest?

When ANC < 100 cell/mm3


What are some common pathogens in FN patients?

Primarily bacterial. Gram (+): Staph aureus, Enterococci, Ciridans group streptococci. Gram (-): E. coli, Klebsiella, P. aeruginoa, Enterobacter. Anaerobes infrequent


What are some prophylactic antimicrobials for FN?

Levofloxacin. TMP-SMX (at risk for Pneumocystis jiroveci). Fluconazole and Acyclovir


What are Low Risk patients for getting infection?

Outpatients. No associated comorbid illness. Solid tumor patients. Serum Cr < 2. LFTs < 3x normal


What are High Risk patients for getting infection?

In-patient. Associated comorbid illness that requires hospitalization. Uncontrolled/progressive cancer. Prolonged neutropenia (< 100 for > 7 days). Pneumonia. Advanced age. Stem cell recipients


What does a score of 21 or higher indicate in the MASCC/IDSA scoring index?

Patient is likely to be at low risk for complications with FN


What is the initial antibiotic regimen to start for FN?

Promptly start broad-spectrum antibiotics. Empiric = reliable coverage of most likely bugs. Bactericidal. Antipseudomonal agent. Stepwise approach if fever persists


What is the usual oral abx used for low risk patients with FN?

Cipro + Amoxacillin-Clavulanate. Reassess after 3-5 days


What are the usual choices for abx in low risk FN patients who require IV treatment?

Cefepime. Ceftazidime. Zosyn. Carbapenem. Aztreonam + Vancomycin (if PCN or cephalosporin allergy). Reassess after 3-5 days


What is reassessment of antibiotic regimen during 1st week like?

At least 3 days of tx usually required to assess efficacy. Time to defervesce for FN cancer patients ranges from 2-7 days


What is done for high risk FN patients who need Vanco?

Vancomycin + Zosyn, Cefepime or carbapenem +/- AG. Reassess after 3-5 days


What is done for high risk FN patients who do not need Vanco?

Two drugs: AG + Zosyn, Cefepime, or Carbapenem. Reassess after 3-5 days


When is Vanco usually added?

B-lactam allergy (vanco + Aztreonam). Catheter-related cellulitis (coag neg Staph). Known colonization w/ PCN- or Ceph-resistant penumococci or MRSA. Isolation of gram positive bacteria from blood. Severe mucositis (Ara-C). Quinolone prophylaxis for afrebrile neutropenia. Clinically unstable (hypotension, septic shock)


What needs to be added to patients regimen if febrile through days 5-7 and resolution of neutropenia is not imminent?

Add antifungals with or without antibiotic change


When can FN therapy be stopped?

If ANC > 500 x2 consecutive days + if afebrile for 48hrs + clinically well


When are systemic fungal infections common in FN patients?

Prolonged (7+ days) and profound neutropenia. Severe mucosal damage. Underlying disease (BMT, AML). Presence of CVC, steroids, broad spectrum antibiotics exposure


What are the most common fungal pathogens in FN patients?

Candida. Aspergillosis. Other molds: Fusarium, Mucor, Rhizopus


What are the Granulocytes-CSF (Colony Stimulating Factors) used?

Filgrastim (Neupogen): 5mcg/kg SQ QD x7-10 days. Pegfilgrastim (Neulasta) - long acting: 6mg fixed SQ once/CT cycle or Q3 weeks


What are the Granulocyte-Macrophage-CSF (Colony Stimulating Factors) used?

Sargramostim (Leukine): 250mcg/m2 SQ daily


What is a caution with Pegfilgrastim (Neulasta) use?

This medication is NOT to be administered during the time interval beginning 14 days before to 24h after administration of chemotherapy


When do you begin CSFs and for how long?

Begin 24-72hrs post chemo. Continue past Nadir until ANC >10,000/mcL (~7-14 days). Alternative: Use for shorter duration until clinically adequate neutrophil recovery, i.e. ANC 2-3,000/mcL


What are the ADRs associated with CSF?

Fever, HA, Bone/joint pain, myalgia (tylenol can be used for these). Injection site reaction. Dyspnea, fluid retention (less common). Splenic rupture