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CHAPTER 95: Toxicities of Chemotherapy 893

TABLE 95-1 Classification of Chemotherapeutic Agents (Continued)
Chemotherapy Class Subclass Individual Agents Example Disease Targets
Biologicals Cytokines IFN-α; IL-2; TNF-α RCC; ovarian; bladder; melanoma; carcinoid; Kaposi; Hairy cell leukemia; CML; MM; NHL
Monoclonal antibodies Trastuzumab HER-2 positive breast
Cetuximab EGFR expressing colon or H&N
Rituximab Lymphoma (CD20 positive)
VEGF inhibitor Bevacizumab Colon; NSCLC
Fusion proteins Etanercept
Tyrosine kinase inhibitors Imatinib CML; GIST
Gefitinib NSCLC; ovarian; breast; colon; H&N
Erlotinib NSCLC
Sunitinib GIST
Sorafenib RCC
Rapamycin analogs Temsirolimus RCC; endometrial; breast; GBM; neuroendocrine tumors
Everolimus RCC; astrocytoma; sarcoma; mantle cell lymphoma
Hormones and antagonists Selective estrogen recep- Tamoxifen, raloxifene ER+ breast cancer
tor modulators
Antiandrogens Bicalutamide, Flutamide, nilutamide Prostate
Aromatase inhibitors Letrozole, anastrozole Adjuvant role in postmenopausal breast cancer patients
GNRH agonists Leuprolide, goserelin Breast; prostate
Somatostatin analog Octreotide Carcinoid; VIPomas
Miscellaneous Glucocorticoids Prednisone Leukemia; lymphoma
Differentiating agent All-trans-retinoic acid (ATRA) APML
Synthetic enzyme Hydroxyurea CML; polycythemia vera; essential thrombocythemia
Proteasome inhibitor Bortezomib MM; mantle cell lymphoma
Immunomodulators Thalidomide MM; MDS; prostate; colon; RCC; breast
Lenalidomide MM; MDS

the American Society of Clinical Oncology indicate that the threshold
TOXICITIES BY ORGAN SYSTEM for prophylactic transfusion varies according to diagnosis, clinical con-
■ MYELOSUPPRESSION dition, and treatment modality. In cases of actively bleeding thrombo-
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cytopenic patients, or those requiring invasive procedures commonly
Myelosuppression due to cytotoxic chemotherapies is a frequent dose- performed in the ICU such as central venous and arterial catheters or
limiting side effect, although it is difficult to identify the precise inci- lumbar puncture, a platelet count greater than 40,000 to 50,000/µL is
dence of anemia, thrombocytopenia, and neutropenia due to potential desired. More invasive surgical procedures with high risk of bleeding or
disease-related effect on the bone marrow. placement of an epidural catheter may require a platelet count greater
Severe anemia (hemoglobin <8 g/dL) can be found in over 70% of than 80,000 to 100,000/µL.
non-Hodgkin lymphoma (NHL) patients receiving CHOP (cyclophos- Neutropenia, defined as an absolute neutrophil count (ANC)
phamide, doxorubicin, vincristine, prednisone) combination chemo- ≤500 cells/mL, predisposes patients to febrile neutropenia and oppor-
therapy; however, the role of chemotherapy in causing the anemia is tunistic infections, an oncologic emergency requiring close monitoring
difficult to distinguish from the disease-related anemia in the patient and hospitalization. Such intensive observation is necessary due to
population. In the absence of symptomatic anemia or evidence of the lack of signs and symptoms of infection without the inflammatory
4
impaired oxygen delivery, a hemoglobin level less than 7 g/dL should response typically mediated by neutrophils. In the absence of clinical
be transfused according to original guidelines published by the British symptoms, there is a 50% likelihood that a patient with febrile neutro-
Committee for Standards in Haematology in 2001; however, there is penia has an established or occult infection (most commonly within
little available evidence to support ideal hemoglobin levels. 5,6 the GI tract, lungs, or skin), while 20% with ANC <500 cells/mL will
Thrombocytopenia has been described in case reports of 16 patients be bacteremic. Causative organisms are typically gram-negative rods
after treatment with rituximab. Mean onset of thrombocytopenia was (E Coli, Klebsiella pneumoniae, Enterobacter sp, Pseudomonas aeruginosa,
19 hours after administration and spontaneously resolved in an average Citrobacter sp, Acinetobacter sp, and Stenotrophomonas maltophilia) or
of 4 days. The mean nadir of platelet count was 12,000/µL with only gram-positive cocci (Staphylococcus sp, Streptococcus sp, Enterococcus
one case of major bleeding (GI) associated with thrombocytopenia. The sp). Factors predicting the risk and morbidity of febrile neutropenia
mechanism remains unclear. Current practice among hematologists, include age greater than 65 to 70 years, comorbid conditions (pneu-
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based primarily on retrospective and few controlled trials more than monia, abdominal pain, neurologic changes), poor performance status,
25 years ago, uses a platelet count of 10 to 20,000/µL, as a threshold dose intensity of chemotherapy, as well as the severity (ANC ≤100 cells/
for prophylactic transfusion. Incidence of severe bleeding events, RBC mL) and duration (>7 days) of the neutropenia. The risk of neutropenia
transfusions, and mortality were not statistically significant when is greatest for hematologic malignancies due to intensity of the treatment
thresholds of 10,000 versus 20,000/µL were compared. Guidelines of regimen and bone marrow involvement of disease. Contrary to what
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