Mary B. Uhlenhopp, RN, MS, MPH
The field of oncology is advancing at a
rapid pace, and oncology nurses are challenged to keep abreast of new
therapies, technologies, and innovations. Available resources to assist nurses
with change are increasing exponentially, and can be both helpful and
overwhelming. While learning about new therapies is crucial, relearning
essentials such as interpreting laboratory data is of equal benefit. With
improved cure rates of some cancers, longer treatment phases, and more
dose-intense regimens, the recognition and management of late effects of
therapies take on greater significance as well.
At the 26th
Congress of the Oncology Nursing Society (ONS) in San Diego, California, nurses
from around the world shared their experiences and expertise for the purposes
of education, enrichment, and collaboration. Compiled here are the highlights
of several sessions on chemotherapy, biotherapy, and their related side
effects. These sessions focused on the past (late effects of therapy), the
present (clinical application of laboratory data), and the future (new
treatments).
As the incidence of childhood cancers has increased,
so too have cure rates. Long-term survivors of cancer therapies are known to
have a greater risk of multiple long-term effects as well as secondary cancers.
Patsy McGuire-Cullen, RN, MSEd, CPNP, CPON, a Pediatric Nurse Practitioner from
Childhood Hematology-Oncology Associates in Denver, Colorado, presented a
review of second or subsequent neoplasms.[1]
Isolating
prior cancer therapy as the cause of subsequent malignancies is difficult if
not impossible. The causes of most cancers remain multifactorial, follow-up for
most late-effects studies is too short, and treatment regimens frequently
change, making conclusions difficult. However, ongoing studies are attempting
to clarify some of the late effects of therapy. From prior studies and clinical
data, it is known that bone and soft tissue sarcomas are more likely to develop
in radiation fields. Female survivors of Hodgkin's disease have a 35-fold
greater risk of developing breast cancer than the general population. Head and
neck cancer patients who have had radiation to the neck region have an
increased risk for thyroid cancer. Patients treated with cranial radiation have
a greater propensity to develop central nervous system tumors.[1]
Treatment
with alkylating agents and anthracyclines carries a low but significant risk of
late effects such as leukemia. With more and more high-dose, dose-intense
therapies and larger numbers of patients receiving bone marrow transplantation,
one could surmise that the number of patients with second malignancies will
also grow. Our role as nurses is to counsel patients to minimize lifestyle and
environmental exposures. Patients should avoid the sun, stop smoking, eat a
low-fat, high-fiber diet, and exercise. Children of patients who received
thoracic radiation should be advised to begin breast self-exam during puberty.
Oncology nurses use laboratory data daily;
however, we could all benefit from a review of the clinical applications of
these data. In a session at the ONS Congress,[2] nurses were re-educated about how
laboratory data can be used not only to assess but to anticipate treatment
response.
Kimberly
Luebbers, RN, BSN, OCN®, an Ambulatory Oncology Nurse from Fletcher Allen Health
Care in Burlington, Vermont, is both a medical technologist and a nurse. Her
valuable presentation shed light on the often dry topic of hematologic
laboratory values.
The causes of
neutropenia are varied (Table 1). Medical oncology nurses calculate the
absolute neutrophil count (ANC) every day (ANC = total white blood cell count
[WBC] x % of neutrophils [segments and bands]). Recent studies recommend using
this calculation and first cycle nadir WBCs (the lowest peripheral blood count
after chemotherapy) after the first chemotherapy cycle to predict a person's
risk for neutropenic episodes (neutrophil count less than 2500/mm3) and the need for supportive growth
factors during the entire course of treatment.
|
Treatment-Related |
|
|
|
|
|
Viral Disease |
|
Lymphocytic, Monocytic Leukemias, Anemia |
|
Marrow Invasion |
|
Drug Induced |
|
|
|
Hypersplenism |
|
Congenital Causes |
New models to
assess first cycle nadir counts are being tested to predict the probability of
subsequent events and determine the need for supportive growth factors early in
the course of treatment.[3-5] The concept behind this model is to
predict the requirement of growth factors, administer the therapy on time, and
minimize or potentially eliminate the need to reduce chemotherapy dose.
Achieving these targets would maximize the potential of therapy.
Optimal
dosing and timely administration of chemotherapy is critical. The use of risk
models such as the Silber model validated by Savvides and colleagues[4] is used to assess risk of nadir events
and determine the need for supportive growth factors, and can offer new and
effective means to improve quality of care.
Ms. Luebbers also reviewed the use of mean
corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red
blood cell distribution width (RDW), reticulocyte count, and erythropoietin
levels as values that can be useful in the prediction, assessment, and
treatment of anemia.
MCV indicates
the size of the red blood cell (RBC). Microcytic, normocytic, and macrocytic
are terms used to identify cell size. MCHC measures the hemoglobin
concentration per unit of RBC volume. MCV and MCHC are used to help identify
the type of anemia (Table 2).
|
Increased MCV |
Decreased MCV |
|
Folic acid deficiency |
Iron deficiency |
|
B12 deficiency |
Thalassemia |
|
Sideroblastic anemia |
Anemia of chronic disease |
|
|
Rheumatoid disease |
|
|
Cancer-related anemia |
|
|
Severe chronic infection |
MCV, mean corpuscular volume
RDW denotes
the size difference among RBCs. This value is useful in predicting anemias
early, before changes occur in the MCV and before signs and symptoms of anemia
occur.
Reticulocyte
count is an indicator of bone marrow activity. The reticulocyte count will be
elevated due to hemolysis or hemorrhage, during treatment for leukemia-related
or pregnancy-related anemia, or during treatment with B12 iron or folic acid.
This value is decreased in anemia related to radiation therapy, adrenal
cortical hyperfunction, and alcohol consumption.
Erythropoietin
is a hormone that is produced primarily by the kidneys. Baseline levels are
helpful to determine possible response to epoetin alfa trials for anemia. In
general, patients with lower baseline erythropoietin levels respond better to
exogenous epoetin alfa than those with higher baseline levels. Although there
is no specific level above which patients will not respond to epoetin alfa, it
is generally suggested that patients with erythropoietin levels greater than
200 mU/mL should not be treated with epoetin alfa.[6]
In summary, the
picture of anemia may present as follows:
·
Normal WBC
·
Hemoglobin and hematocrit decreased
·
MCV decreased
·
MCHC decreased
·
RDW decreased
·
Platelets increased
·
Serum ferritin level decreased
·
Serum iron level decreased
·
Iron binding capacity increased
With antiangiogenesis inhibitors,
epidermal growth factor receptor inhibitors, enzyme inhibitors, gene therapy,
photosensitizers, and other new biotherapeutic agents flooding the field,
oncology nurses are challenged to understand the therapeutic mechanisms and
know the names or abbreviations of therapies being evaluated.
Over the
years, the volume of research devoted to chemotherapies and biotherapies has
increased significantly. Searching cancer trials on the Internet via the National
Cancer Institute (NCI) Physician Data Query system at
http://cancertrials.nci.nih.gov reveals that, including the NCI and other
cooperative groups worldwide, there are:
·
736 biologic response modifier trials
·
414 cytokine therapy trials (76 of which are anticytokine studies)
·
71 antiangiogenesis trials
·
23 gene therapy trials
·
17 kinase inhibitor trials
The Pharmaceuticals Research and
Manufacturers of America recently reported that there are 402 cancer
medications in the pipeline, compared with 215 medications 6 years ago.[7] At the ONS Congress, several speakers
clarified the actions and uses of many of the newer therapies. A few key
therapies are presented here.
Major
advances in the understanding and identification of genes, cell characteristics,
cell proteins, and receptors have paved the way toward new, more targeted
therapies. Deborah Rust, RN, MSN, CRNP, AOCN®, Coordinator of the Oncology Nurse
Practitioner Program at the University of Pittsburgh, Pennsylvania, and Kristi
Kay Orbaugh, RN, MSN, RNP, AOCN®, of Indiana Oncology Hematology Consultants, Indianapolis,
Indiana, provided a comprehensive overview of new molecular targeted therapies,
updated new therapies, and thoughtfully reviewed the process of tumor growth.[8]
The
proliferation of tumors is a result of either the activation of an oncogene or
the deactivation of tumor suppressor genes.[9] These processes lead to the development
of abnormal or excessive proteins. Protein products initiate coordinated
signals on the cell surface, such as the binding of growth factors to receptors
on the cell surface. The binding activates enzymes that communicate within the
cell to activate signal transduction. The overexpression of proteins on the
cell surface leads to structural alterations of the cell or alteration of the
signal transducers. The result of this series of alterations is the development
of malignant cell characteristics: uncontrolled cell proliferation, loss of
contact inhibition, and the development of resistance to therapy.
Tyrosine
kinase inhibitors. Tyrosine kinase inhibitors inhibit signal transduction and
cell growth. The overexpression of epithelial growth factor receptors has been
associated with several types of cancer. Therapies that target these and other
such receptors are examples of tyrosine kinase inhibitors and signal
transduction inhibitors. Trastuzumab (Herceptin) interferes
with an epidermal growth factor receptor binding to receptor and inhibits
proliferation. Other tyrosine kinase inhibitors under evaluation are IMC C225,
ZD 1839 (Iressa), CCI 779, and SU 101.[10-13] Of special note is the unusually rapid
US Food and Drug Administration (FDA) approval of imatinib mesylate (Gleevec)
on May 10, 2001.
Imatinib
mesylate is the first approved drug to directly turn off the signal of a
protein known to cause cancer.[13] Other molecular-targeting drugs interfere with proteins
associated with cancer but not with proteins that directly cause the disease.
Imatinib mesylate was initially developed to treat chronic myelogenous
leukemia; however, it now appears to work in a rare type of cancer called
gastrointestinal stromal tumor. It is also being evaluated in clinical trials
for glioblastoma and leukemia. Imatinib mesylate is administered orally and its
side effects include swelling, cramps, nausea, and, in some cases, severe
anemia. Long-term effects are unknown at this time.
IMC C225,
like trastuzumab, is a monoclonal antibody that prevents tyrosine kinase
activity. It is an antiepidermal growth factor receptor and inhibits
proliferation.[10] IMC C225 is not yet FDA-approved, and it is being
evaluated for colorectal cancer as a single agent and in combination with
chemotherapy agents.
ZD-1839 is
another investigational oral epidermal growth factor tyrosine kinase inhibitor
that has been tested alone and in combination with various cytotoxic agents in
ovarian, breast, and colon cancer.[14] It is being evaluated in lung and prostate cancers as
well. In combination with chemotherapy, apoptosis (cell suicide) was markedly
increased.
Alemtuzumab (Campath
IH) was also recently approved by the FDA and is a monoclonal antibody
that binds to CD52 on T and B cells in prolymphocytic or chronic lymphocytic
leukemia that has become refractory.[15] Major side effects include allergic
reactions and possible severe leukopenia and/or prolonged protracted
pancytopenia. Consequently, patients are treated prophylactically with
antibiotics, antifungals, and antivirals during therapy and for 3 months after
the completion of therapy.
The field of antiangiogenesis agents is a
vital area of research. It has taken years of investigation to learn how to
decipher and interrupt the genetic control of tumors since Dr. Judah Folkman
introduced the concept of angiogenesis in 1971.[16] Ms. Rust reviewed the concept of
angiogenesis and described how tumors cannot grow beyond 1 mm to 3 mm without
developing new vasculature. A collection of tumor cells requires the
nourishment of oxygen for growth. The further the tumor is from major blood
vessels, the lower the rate of cell replication; and the denser the blood
vessel formation, the higher the rate of tumor formation and the greater the
metastatic potential.
Carol Hill,
RN, OCN®
from Emory University in Atlanta, Georgia, reported on carboxyamidotriazole
(CAI).[17]
CAI is an oral angiogenesis inhibitor that was first developed to treat
parasites in chickens. It was found to inhibit a broad spectrum of tumor cells
such as melanoma, lymphoma, prostate, colon, renal, and brain tumor cells. It
was then chosen for development because of antiproliferative and antimetastatic
activity against several human tumor cells in vitro and in vivo. It appears to
cut off blood supply to cancer cells by inhibiting certain proteins involved in
signal transduction by inhibiting calcium influx.[12]
Other
antiangiogenesis agents under investigation include marimastat, neovastat,
endostatin, thalidomide (being investigated for "off-label"
activity), SU5416, SU6668, interferon alfa, suramin, and others (Tables 3-6).
|
Drug |
Trial |
Mechanism |
|
Marimastat |
Phase 3 small-cell lung, breast cancers |
Synthetic inhibitor of MMPs |
|
COL-3 |
Phase 1/2 brain cancer |
Synthetic MMP inhibitor, tetracycline
derivative |
|
Neovastat |
Phase 3 renal cell (kidney) cancer.
Phase 3 nonsmall-cell lung cancer |
Naturally occurring MMP inhibitor |
|
BMS-275291 |
Advanced or metastatic nonsmall-cell
lung cancer |
Synthetic MMP |
Adapted from http://cancertrials.nci.nih.gov/news/angio/table.html. MMP, matrix
metalloproteinase
|
Drug |
Trial |
Mechanism |
|
Thalidomide |
Phase 1/2 for advanced melanoma. Phase 2
ovarian cancer, metastatic prostate cancer, and Kaposi's sarcoma. Phase 2
with chemotherapy against solid tumors; adjuvant study in recurrent or
metastatic colorectal cancer. Phase 2 gynecologic sarcomas, liver cancer,
multiple myeloma, chronic lymphocytic leukemia. Phase 3 nonsmall-cell lung
cancer, nonmetastatic prostate cancer, refractory multiple myeloma, renal
cancer. |
Inhibits cell proliferation |
|
Endostatin |
Phase 1 solid tumor studies |
Inhibition of endothelial cells |
Adapted from http://cancertrials.nci.nih.gov/news/angio/table.html
|
Drug |
Trial |
Mechanism |
|
SU 5416 |
Phase 1 recurrent head and neck cancer,
advanced solid tumors, stage IIIB or IV breast cancer. Phase 1 advanced
malignancies. Recurrent or progressive brain cancer (pediatric). Phase 1 with
chemotherapy against solid tumors. Phase 1/2 acute myeloid leukemia, advanced
malignancies, advanced colorectal cancer, recurrent brain cancer. Phase 2 von
Hippel-Lindau disease, advanced soft tissue cancer. Phase 2 prostate cancer,
metastatic melanoma, multiple myeloma, malignant mesothelioma, metastatic
renal cancer, advanced or recurrent head and neck cancer. Phase 3 metastatic
colorectal cancer. |
Blocks VEGF receptor signaling |
|
SU 6668 |
Phase 1 against advanced tumors |
Blocks VEGF, FGF, and PDGF receptor
signaling |
|
Interferon-alfa |
Phase 2/3 renal cancer, myeloid
leukemias, melanoma, myeloma, prostate cancer, lymphoma, meningioma. |
Inhibition of bFGF and VEGF production |
|
Anti-VEGF antibody |
Phase 1 refractory solid tumors. Phase 2
metastatic renal cell cancer. Phase 2 with chemotherapy in untreated advanced
colorectal cancer, metastatic breast cancer. Phase 3 with chemotherapy in
untreated metastatic colorectal cancer. |
Monoclonal antibody to VEGF |
Adapted from http://cancertrials.nci.nih.gov/news/angio/table.html. VEGF,
vascular endothelial growth factor; FGF, fibroblast growth factor; PDGF,
platelet-derived growth factor; bFGF, basic fibroblast growth factor
|
Carboxyamidetriazole |
Phase 1 studies in combination against
solid tumors. Phase 2 ovarian cancer, metastatic renal cell cancer. |
Inhibitor of calcium influx |
|
Interleukin 12 |
Phase 1/2 Kaposi's sarcoma |
Upregulation of interferon gamma and
IP-10 |
|
IM 862 |
Phase 1 recurrent ovarian cancer. Phase
2 for untreated metastatic cancers of the colon and rectum; Phase 3 Kaposi's
sarcoma |
Unknown mechanism |
Adapted from http://cancertrials.nci.nih.gov/news/angio/table.html
In summary,
oncology nurses can provide higher quality care to patients when they are
knowledgeable and up-to-date about new therapies, new assessment and monitoring
techniques, and other topics important in the care of the patient with cancer.
1.
McGuire-Cullen P, Ruccioni K, Ruble K. The long and short of it:
assessment and management of late effects. Program and abstracts of the 26th
Congress of the Oncology Nursing Society; May 17-20, 2001; San Diego,
California. Instructional Session 27.
2.
Ireland AM, Luebbers KP, Singer M. Fitting the pieces together: clinical
application of laboratory data. Program and abstracts of the 26th Congress of
the Oncology Nursing Society: May 17-20, 2001; San Diego, California.
Instructional Session 2.
3.
Thomas ES, Rivera E, Erder H, Fridman M, Frye D, Hortobagyi GN. Using
first cycle nadir absolute neutrophil count (FCNANC) as a risk factor for
neutropenic events: a validation study. Program and abstracts of the 37th
Annual Meeting of the American Society of Clinical Oncology; May 12-15, 2001;
San Francisco, California. Abstract 144.
4.
Savvides P, Terrin N, Erban J, Selker HP. Development and validation of
a patient-specific predictive instrument for the need for dose-reduction in
chemotherapy for breast cancer: a potential decision aid for the use of myeloid
growth factors. Program and abstracts of the 37th Annual Meeting of the
American Society of Clinical Oncology; May 12-15, 2001; San Francisco,
California. Abstract 972.
5.
More T, Shiftan TA, Knight CA, et al. A prospective trial assessing a
risk model for filgrastim use on chemotherapy (CT) dose intensity (DI) in the
adjuvant treatment of stage I-II breast cancer patients. Program and abstracts
of the 37th Annual Meeting of the American Society of Clinical Oncology; May
12-15, 2001; San Francisco, California. Abstract 1778.
6.
Medscape DrugInfo. Epoetin alfa injection: uses & dosage. Available
at: http://promini.medscape.com/drugdb/drug_uses_dosage.asp?DrugCode=2%2D4553&DrugName=EPOETIN+ALFA+INJECTION&DrugType=1.
Accessed June 8, 2001.
7.
Pharmaceutical Research and Manufacturers of America. PhRMA survey finds
402 medicines in the pipeline for cancer. March 29, 2001. Available at:
http://www.phrma.org/press/newsreleases//2001-03-29.203.phtml. Accessed May 28,
2001.
8.
Orbaugh KK, Anton ML, Rust DM, Binnie C. Hot topics -- clinical. Program
and abstracts of the 26th Congress of the Oncology Nursing Society; May 17-20,
2001; San Diego, California. Instructional Session 17.
9.
DeVita T Jr, Hellman S, Rosenberg SA, eds. Principles &
Practices of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven;
1997: 3087-3092.
10. Waksal HW. Role of an anti-epidermal
growth factor receptor in treating cancer. Cancer Metastasis Rev.
1999;18:427-436.
11. Ciardiello F, Caputo R, Bianco R, et al.
Antitumor effect and potentiation of cytotoxic drugs activity in human cancer
cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective
tyrosine kinase inhibitor. Clin Cancer Res. 2000;6:2053-2063.
12. Strawn LM, Kabbinavar F, Schwartz DP, et
al. Effects of SU101 in combination with cytotoxic agents on the growth of
subcutaneous tumor xenografts. Clin Cancer Res. 2000;6:2931-2940.
13. Cancer Trials, National Cancer Institute.
Digest page: STI571 (GleevecTM). Available at:
http://cancertrials.nci.nih.gov/types/leuk/sti571/index.html. Accessed May 27,
2001.
14. Pitot HC, Golberg RM. Future directions
in adjuvant therapy for stage III colon carcinoma. Oncology. 2001;15(suppl
5):31-36.
15. Weiss MA. Novel treatment strategies in
chronic lymphocytic leukemia. Curr Oncol Rep. 2001;3:217-222.
16. Brem S. Angiogenesis and cancer control:
from concept to therapeutic trial. Available at:
http://www.moffitt.usf.edu/pubs/ccj/v6n5/article2.htm. Accessed May 27, 2001.
17. Hill C. Carboxyamidotriazole (CAI), an
oral antiangiogenic agent: nursing implication of phase II clinical trials.
Program and abstracts of the 26th Congress of the Oncology Nursing Society; May
17-20, 2001; San Diego, California. Abstract 8.
Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.