Introduction

Cancer Treatment Types

Cancer is treated by one or more modalities. These modalities are: surgery, radiation therapy, chemotherapy, and biotherapy. Surgery and radiation therapy are localized treatment, as their outcomes are based on local or regional responses. Chemotherapy and biotherapy, as the title of this course suggests, are systemic therapies with the goal of targeting more than one localized area.

Although this course focuses on chemotherapy and biotherapy, an important point to remember is that oftentimes a cancer treatment regimen includes more than one modality. If the treatment plan includes more than one modality, this is referred to as multimodal therapy. More than likely, unless all treatment is refused, at some point throughout the cancer journey a patient will encounter some form of at least one cancer treatment modality.

For an overview of all cancer treatment modalities, please refer to the CEU4U course entitled "Understanding Cancer Treatment Modalities." For an in-depth look at radiation therapy, please refer to the CEU4U course entitled "Radiation Therapy: Traditions and Trends."

Treatment Decision

Cancer treatment decisions are based on the location, cell type, extent of disease, and patient factors. Planning each patient's treatment is an individualized process and consists of gathering and analyzing clinical subjective and objective data. The steps in treatment decisions are as follows: the patient presents symptomatically or asymptomatically, a screening and/or diagnostic workup is done followed by a biopsy to establish diagnosis, and the tumor is then pathologically staged and classified.

For the most part, treatment decisions are based on prognosis, clinical data, anticipated response, and individual health history. Interdisciplinary collaboration is utilized and usually involves several physicians, such as the patient's primary care physician, radiologist, pathologist, surgeon, oncologist, and/or another specialist (gastroenterologist, urologist, gynecologist, etc). Many times, research nurses, advanced practice nurses, social workers, dietitians, pharmacists, and physicists are involved in the initial treatment planning to discuss pertinent patient and clinical information. Some cancer treatment centers have initiated the concept of "care conferences" for specific diseases, such as breast, lung, and prostate cancers. Following these collaborative efforts, the patient and family members are then presented with treatment options and appropriate education so they can make an informed decision.

Treatment Goals and Response

The purpose and goal of cancer treatment may be to cure, control, or palliate the disease. Each patient's treatment goal is individualized based on the type and invasiveness of cancer and the cancer's known response to treatment. To cure cancer in adults means the goal of treatment is to have no evidence of disease for five years or more following treatment. In the pediatric population, a cure means there is no evidence of disease for two years or more following treatment. To control cancer means the goal of treatment is to control or limit cancer growth and to control the side effects of the cancer when a cure is not realistic. To palliate (or palliation) means to control side effects and maintain quality of life through treatment when a cure or control of the disease is not considered possible.

An additional goal of cancer treatment may be stated as prophylaxis. Prophylactic chemotherapy is considered to be adjuvant or neoadjuvant therapy. If surgery is performed then chemotherapy or radiation is administered, the subsequent chemotherapy or radiation therapy is referred to as adjuvant therapy. In other words, the surgery is considered the primary treatment and the adjuvant treatment is given as a precaution to help control or limit cancer growth. The goal of adjuvant chemotherapy is to systemically control micro or distant metastasis. However, sometimes tumor burden is very great and surgery may not be possible upon diagnosis. When the tumor size is a factor that may complicate surgical removal, sometimes an option is to give chemotherapy or radiation therapy prior to surgery. This is referred to as neoadjuvant therapy. If chemotherapy is administered, one or more courses may be given with the goal of reducing tumor burden so a less radical surgery can be performed and/or surgical complications are fewer.

Drug Development

The development of drugs used to treat cancer, whether they are chemotherapy or biotherapy agents, and other diseases is a long, involved, and monitored process. From the time of initial identification, 10-15 years usually elapses before a drug is FDA-approved and available on the market with specific diagnosis-related indications for use. A series of studies is performed and evaluated prior to drug approval.

The initial studies that begin the process of evaluating drugs involve laboratory in vitro, in vivo, and animal studies. These studies determine stability and solubility of the drug or agent. They also determine the maximum tolerated animal dose. When safety and efficacy is demonstrated in a potential new agent based on these laboratory studies, the sponsoring company or research center files an Investigational New Drug Application with the FDA. Following FDA approval for human research, the drug is then allowed to move into the human testing arena. Studies that involve testing of the agents in humans are called clinical trials.

Clinical trials are often called protocols, studies, or roadmaps. Cancer clinical trials provide the scientific study of a new antineoplastic agent or a combination of agents in humans. The purpose of these studies is to evaluate the safety, efficacy, and adverse effects (toxicities) of new agents or combination of agents.

Cancer clinical trials are developed by independent researchers, pharmaceutical companies, and national study groups. When national study groups are involved, they develop the various parts of the study design then offer the study to all institutions with which they are affiliated. For example, some study groups that are affiliated with institutions that perform clinical research are the Southwest Oncology Group (SWOG), the Eastern Cooperative Oncology Group (ECOG), the Children's Oncology Group (COG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP). Pharmaceutical companies develop clinical trials involving their drugs and can offer the studies to institutions. Independent researchers are those interested in certain regimens or treatment effects and set up studies of their own.

Approval and Eligibility for Clinical Trials

All clinical trials, regardless of their origin, must be approved by an institutional committee prior to enrolling any patients. This committee, the Institutional Review Board (IRB), evaluates the safety and ethics of the study to determine if it can and should be utilized within the institution. Without this committee's approval, a study cannot be conducted within an institution.

To be enrolled in a clinical trial, the trial must be available at the institution where the patient is being treated. Physicians and research nurses typically share the responsibility of identifying a patient who is eligible for a trial. The patient must meet strict eligibility criteria. Criteria for eligibility vary in each study. If a patient has even one problem or issue that is not acceptable by the study requirements, that patient cannot participate in the study. A study involves a strict timeline. The timeline involves the length and frequency of treatments as well as diagnostic testing to monitor progress. Doses of the agents and, sometimes, adjuvant agents or pre/post medications are determined by the study design itself. Failure to comply to proper dosing criteria, follow-up testing, and data submission could result in the patient being removed from the study.

Patient and Family Education and Informed Consent

Prior to being enrolled in a clinical trial, a patient and his/her family are involved in an intense educational process. The patient and/or parent or guardian is required to sign a consent form that involves all aspects of informed consent. The patient or individual giving consent must be informed of why the study is being performed, the goals of the study, all potential risks, all potential benefits, all potential toxicities, all expectations of testing and follow-up, and of any financial stipulations or responsibilities. The consent form is then signed by the patient, the research nurse and the treating physician. Note: a simple hospital inpatient consent form, although signed upon each admission, is not sufficient for initial consent for a clinical trial.

Enrollment is voluntary. Once enrolled in a study, a patient or parent/guardian may elect to be removed from it at any time. Likewise, the physician may remove a patient from the study at any time if serious toxicities or other developments occur. However, a patient and physician may decide to "follow" a study even if they are not eligible. This means the agents used for treatment are indicated for their disease and can be used, but the data collected in regards to toxicities, quality of life, and survival will not be analyzed.

Phases of Clinical Trials

There are essentially 3-4 phases of drug development and testing in humans. Each phase has its own purpose, goals, and objectives. As stated above, each study has its own set of eligibility requirements for patient enrollment. As each agent progresses through the different trial phases, new studies with new goals and objectives are developed.

Phase 1 Trials. This is the first phase of drug testing in humans. The primary objectives of a Phase 1 study are: a) to determine the maximum tolerated dose (MTD) or the optimal biologic dose (OBD) of the experimental agent, b) to determine the mechanism of action of the agent within the human body, and c) to determine the side effects and toxicities of the agent. These trials usually involve a small number of patients and are considered highly experimental. Phase 1 studies usually begin with adult patients and after the maximum tolerated dose for adults has been established, the trial may then include pediatric patients. Additionally, many patients in a Phase 1 study have already been treated with standard therapy and either did not respond or they have suffered one or more relapses. A Phase 1 study usually only continues in children if the agent is beneficial to the patient; other options are discussed if the agent is not effective.

Phase 2 Trials. After adequate data has been collected from a Phase 1 trial and the agent has been determined as having a safe maximum dose and side effects or toxicities can be effectively managed, the agent can progress to a Phase 2 trial. The objective of a Phase 2 study is to test the ability of the agent to produce measurable tumor shrinkage in patients with the same type of cancer. Sometimes, the agent is combined with other agents for a Phase 2 study. As with Phase 1 pediatric trials, usually a pediatric Phase 2 study includes children whose cancer is no longer responding to standard treatment.

Phase 3 Trials. Upon adequate data collection from Phase 2 studies and upon the FDA's determination that the agent or combination of agents is indeed efficacious, the agent or combination can progress to a Phase 3 trial. Phase 3 trials compare two or more treatments for a particular type of cancer and also collect quality of life data and survival statistics. For example, a Phase 3 study may compare a usual standard treatment with a new agent or combination of agents to determine if the new treatment is more effective and results in better quality of life for one type of cancer. Or, a Phase 3 study may compare two newer treatments to determine which is more effective with a better quality of life for one type of cancer. Sometimes, more than two treatments are studied and evaluated in a Phase 3 trial. Phase 3 trials are randomized trials, meaning that patients are "randomly" assigned (like "flipping a coin") to one treatment or another and each treatment being studied is referred to as an "arm" of the study. The physician, patient, and research nurse have no control over into which "arm" of the study a patient will be enrolled. This random assignment process is not affected by any patient characteristics. Therefore, when a patient agrees to be enrolled in a Phase 3 trial, he or she does not know which treatment they will receive until the enrollment process is complete. If enrolled in a Phase 3 trial, patients are usually asked to track and document symptoms and side effects to obtain quality of life information. Phase 3 studies usually involve large numbers of patients to substantiate data results.

At the completion of a Phase 3 study, the FDA will analyze the data and determine if more testing is needed. If the FDA determines more data is needed before full approval for use can be granted, the sponsoring company will be required to continue testing on the agent or combination of agents and re-submit data at a later date for re-evaluation. If the FDA determines the agent or combination of agents has been tested in a sufficient number of patients and if it has been proven safe, effective, and has shown benefit over standard treatment, the agent or combination of agents will most likely be approved, recommended, and indicated as a "new" first-line standard treatment for that particular type of cancer. If the agent or combination of agents is safe and effective, but does not necessarily show benefit over the previous standard treatment, the FDA may approve it, but may only recommend and indicate it as an alternative to the standard treatment or as a "second" or "third" line treatment should standard first-line treatment fail. Once an agent or combination of agents has been FDA-approved, further "post-marketing" (Phase 4) studies may or may not be performed. Phase 4 trials are not required by the FDA.

Phase 4 Trials. Phase 4 trials are those that take place following FDA-approval of an agent or combination of agents. Phase 4 studies are usually developed, sponsored, and/or conducted by pharmaceutical companies. The goal of a Phase 4 trial is mainly to evaluate whether the agent or combination of agents is effective in different types of cancer other than those types for which it has already received approval. These trials also involve quality of life information and survival statistics in large numbers of patients. If results of a Phase 4 study show that the treatment is indeed efficacious in different types of cancer, the FDA will most likely state it is now indicated for use in that tested type of cancer.

Not all institutions can perform all phases of a trial. The FDA permits only certain types of institutions to perform Phase 1 studies. Most community institutions conduct Phase 2, 3, and 4 studies, while the Phase 1 studies are conducted at academic institutions.

The terms remission or response are often used interchangeably. A clinical response to treatment is measured using objective criteria (scans, lab results, tumor markers, etc.) and comparing them to baseline data on a periodic and ongoing basis. Response is stated as "complete", "partial", or "minimal". Other terms utilized in describing treatment response are "stable disease" and "disease progression".

Response can also be measured using subjective data (quality of life, pain, fatigue levels, etc.) which is frequently utilized to gather data for research. However, objective criteria is the main source of measuring the actual clinical response to treatment.

When discussing a treatment response or disease relapse, another term utilized is tumor cell resistance. As previously mentioned, a tumor can be resistant or refractory to cancer treatment. Resistance can be temporary or permanent. Such tumors may have intrinsic resistance, meaning they are resistant even prior to exposure to treatments. These tumors can actually thrive during treatment. Other tumors may have acquired resistance. This means they initially respond well to treatment, but develop resistance later (usually within six months) and begin to grow rapidly again. Changing treatment types or drugs can sometimes help, but some tumors can be multi-drug resistant. Why this happens remains a mystery. Some theories relate tumor resistance to cell enzymes and the changes in these enzymes during treatment. Refractory is another similar term utilized to describe a tumor that has recurred or persisted despite treatment. Much research is being done on these very resistant tumors.

Other factors are involved in how a patient responds to treatment. Tumor type, tumor burden, hormone status of the tumor, and the treatment regimen given can all affect a patient's response to treatment.

For instance, the size and location of the tumor itself can affect response. Again, generally stated, the larger the tumor, the harder it is to treat. The hormone status of the tumor also affects response. This is, of course, only true of hormone-related tumors, such as breast cancer. Some breast cancers depend on estrogen, progesterone, or both to thrive. These tumors usually respond differently (and better) to treatment than those that are not dependent on hormones. The hormone receptor status is determined in the pathologic examination of the tumor tissue.

Chemotherapy

As stated previously, chemotherapy is just one modality of cancer treatment and is systemic in its administration and effect. Chemotherapy administration has many entities and potential complications.

History of Chemotherapy

Chemotherapy was first used in the 1500's when heavy metals were used to treat cancer, resulting in limited effectiveness and lethal toxicities. One of the first major developments in chemotherapy occurred following World War I. The first "modern-day" agent was discovered at this time. Mustard gas was used as chemical warfare during the war and its myelosuppressive effects on the servicemen exposed to it led to the discovery and eventual use of nitrogen mustard as the first modern chemotherapy agent. It is still used today, mostly for the treatment of Hodgkin's Disease.

World War II and the 1940's and 50's brought the passing of the National Cancer Institute (NCI) Act and the National Chemotherapy Program, resulting in Congressional funding and recognizing cancer research as a health priority. During this time, folic acid antagonists and the antitumor antibiotics (anthracyclines) were discovered.

During the 1960's and 70's, many important advances were made but funding was not readily available. First, the platinum compounds and doxorubicin were beginning to be developed, both of which would be mainstays of cancer chemotherapy for most of the 80's and 90's. Also, multiagent chemotherapy regimens, multimodal therapy, and adjuvant therapy were tested and discovered to be efficacious in many diseases, all of which continue to be used today. Additionally, the National Cancer Act was created in 1971 which greatly improved research funding opportunities.

The 1980's brought community cancer programs into existence, allowing greater access to and increased accruals for clinical trials. Quality of life and symptom management were the focus of much research in order to find ways to effectively treat chemotherapy toxicities. Many new chemotherapy agents were developed and approved in this decade and research on cytoprotectants began.

The decade with the most advances in cancer chemotherapy thus far was the 1990's. Comprehensive cancer centers, community programs, and cooperative research groups grew exponentially in numbers. The first cytoprotectants and growth factors were developed along with many new chemotherapy agents, including the taxanes and hormonal therapy. Great strides in antiemetics were made with the development and approval of the 5HT3 serotonin antagonists. Much research on the genetic basis of cancer was beginning and the knowledge from these research efforts came quickly.

The 21^st century promises to bring dozens more chemotherapy agents and regimens to the forefront. Biotherapy, which will be discussed later, is experiencing much research and development, such as gene therapy and targeted treatment. The next decade or so promises treatment that can target cancer cells while limiting exposure to normal cells.

Principles of Chemotherapy

The effectiveness of chemotherapy drugs depends on the cell type of the cancer being targeted and the drug's action during the cell life cycle. Drugs are classified according to this pharmacologic action during the cell cycle. Basically, chemotherapy agents work by inhibiting or preventing cellular division (mitosis) and/or by damaging cellular DNA or RNA.

The cell life cycle, as a review, consists of five phases. If all phases progress normally, the end result is cellular proliferation, or reproduction. The same cell cycle is followed for both normal and malignant cells. The five phases are as follows:

G-0 or resting phase. This is the first phase when the cell is first formed and is essentially dormant.

G-1 or post-mitotis phase. This phase is the start of the reproductive process. The enzymes that are needed for cellular DNA are produced. RNA synthesis is also occurring at this time.

S or synthesis phase. During this phase the cellular DNA is produced.

G-2 or pre-mitosis phase. RNA synthesis is completed and more proteins are produced. These allow formation of the mitotic spindles.

M or mitosis phase. This phase is the all important phase of reproduction and is actually divided into four subphases: prophase, metaphase, anaphase, and telephase.

Chemotherapy agents are classified as either cell-cycle specific or cell-cycle nonspecific. Cell-cycle specific agents exert their effect within a specific phase of the cell cycle. These drugs are dependent on a fairly stringent administration schedule to work effectively, meaning they work best when given in divided doses or as a continuous infusion. Most of these agents work during the S phase. Cell-cycle nonspecific agents are effective during any phase of the cell cycle, even during the resting phase. These drugs are not so much dependent on the schedule of administration as they are dependent on the dose given. Therefore, their effectiveness is directly related to the amount of drug given (the higher the dose, the better the effect).

Because of their different mechanisms of action, cell-cycle specific drugs are more effective on small, rapidly dividing tumor cells. Cell-cycle nonspecific drugs, on the other hand, have a better effect on larger tumors with fewer dividing cells.

Oftentimes, cell-cycle specific agents will be given in conjunction with cell-cycle nonspecific agents. This is called combination or multiagent therapy and is utilized to maximize cell kill, and reduce the possibility of drug resistance. However, prior to clinical trials or studies involving combination drug therapy, each drug is assessed for the types and extent of toxicities they cause as well as their efficacy. To increase efficacy, the drugs used together in these multiagent regimens need to have a synergistic effect. Simply put, they need to be able to work well together despite their differing mechanisms of action and they should have different or minimally overlapping toxicities to avoid organ dysfunction.

Many theories exist concerning the pattern of tumor cell growth. The most widely accepted and taught theory is the Gompertzian theory. This theory states that a cancer cell begins with a mutation within the cell cycle that causes abnormally rapid cellular proliferation and cell growth. The abnormal mutated cells have distinctly different structure and growth patterns than normal cells. As the cells continue to reproduce, they form a tumor. This theory suggests that when tumors are small, their proliferate very rapidly. However, as the tumor gets larger, proliferation continues but becomes slower and slower over time.

From the Gompertzian growth theory comes the well-known statement "the smaller the tumor, the higher the rate of cure." It is widely believed that malignant tumors respond better to treatment when they are small because there are more cells in active reproduction than when a tumor is larger. This is also a reason for the belief that prevention and early detection are so important.

Chemotherapy drugs can be administered orally, by subcutaneous or intramuscular injection, intravenously, intrathecally, or intracavitarily, based on the drug's purpose, action, and vesicant potential. Administration routes and schedules for chemotherapy regimens differ depending on the cell type, the drug's mechanism of action, and patient response. The scheduling of chemotherapy treatments also varies. Some schedule examples include a treatment five days in a row for several weeks followed by a rest period, a treatment every week, or a treatment every 21 - 28 days. The schedule and duration of each regimen are individualized based on disease factors, patient status, and clinical research results.

Dosing of chemotherapy agents is based on standard doses that have been established through research and clinical trials. The dose is calculated by body surface area (BSA), which is measured by height and weight. The exact method of dose calculation will be discussed in the next section. One agent that may or may not be dosed this way is carboplatin, which can also be dosed based on a calculation that involves renal function and the glomerular filtration rate. This method of dosing is referred to as area under the curve (AUC) dosing. Other exceptions to the use of BSA in dosing are obese patients and those experiencing organ or severe toxicities.

Standard dosing is most frequently used in treatment regimens and is based on the known maximum tolerated dose. However, high-dose therapy is used in certain diseases (e.g. acute leukemia induction), in certain treatment regimens (e.g. bone marrow or stem cell transplant), and sometimes in pediatric regimens. The goal of high-dose therapy is that a higher than standard dose of a regimen is given in an attempt to completely eradicate the disease and the bone marrow. The ultimate goal is to eradicate all bone marrow stem cells and, upon their regrowth, to have all new fresh cells that will have no abnormalities. A high-dose procedure is usually followed by an intense observation period and a rescue of some type (bone marrow, stem cells, supportive therapies, growth factor, etc.). Another type of therapy is known as dose intensification which utilizes 10 - 200 times the standard dose and is given in a number of ways, including a single high dose, divided doses over more than one day, and a long-term infusion. Dose intensification is used mostly with aggressive diseases and in patients whose organs can tolerate a higher dose. Growth factors, which will be discussed later, are usually given in conjunction with dose intensive treatments.

The following steps are those taken to determine the doses to be administered in an antineoplastic regimen. They are actually the same steps utilized to determine the dosage of many non-chemotherapy drugs, especially those used in pediatric populations. These steps are crucial and should be performed by at least three oncology professionals: the physician writing the order, the pharmacist or nurse preparing the regimen, and the nurse administering the regimen. Many institutions require two nurses to verify doses prior to administration, a very prudent and reassuring process that takes patient safety one step further and demonstrates nursing excellence.

Step 1:            Compare written order with the patient?s protocol if the patient is on a clinical trial.   If the patient is not a clinical trial participant, use an up-to-date oncologic pharmacology reference.   Locate the standard dose in the reference or the intended dose in the clinical trial protocol.  Also locate the ordered/intended dose on the physician order form.

Step 2:            Obtain the patients actual height and weight.  A stated height and weight is not sufficient and is unacceptable.  Additionally, the height and weight must be consistently termed.  In other words, both the height and weight must both be stated either in American or metric measurements (pounds and inches OR kilograms and centimeters). Mixing the terms of measure will produce an incorrect BSA when using this equation.

Step 3:           Calculate the body surface area (BSA) utilizing the equation below or a BSA nomogram or calculator.  The actual equation must be utilized on pediatric patients and is usually required for clinical trial patients.  Many institutions are now requiring this equation to be used on all patients.  Otherwise, the use of a nomogram or BSA calculator that are available through many pharmaceutical companies is acceptable providing the institutional policy allows this.  BSA is written and stated in terms of m² .

Step 4:            Determine the drug dose by multiplying the standard or intended dose by the BSA.   Many times, doses are rounded up or down to the nearest and most convenient admixture dose.  However, pediatric doses must be exact and most clinical trials require doses to be exact.

Step 5:            Verify results with a colleague and clarify or notify with the pharmacist or physician for any discrepancies.  Do not administer any agents if a discrepancy exists.

Sometimes if a discrepancy exists in the ordered dose and calculated dose, there is a sufficient and explainable reason. The patient may have needed a dose reduction due to a toxicity or organ dysfunction concern. Or, the patient may be receiving a dose intensification. Another reason may be the patient's weight. An obese patient should not receive a dose based on actual weight. Ideal body weight is usually used in this instance.

The best action should a discrepancy occur is to check the physician progress notes for any notation of the reason for a dosage change if a discrepancy exists. If there is no explanation, notify the physician of the discrepancy.

In addition to the importance of how, when, and how much of a treatment is administered, another critical issue is whether single or combination therapy is planned. As noted previously, a combination regimen usually includes cell cycle specific and nonspecific agents to assure maximum tumor cell kill. Using more than one agent also minimizes the possibility of tumor cell resistance. Just as a microorganism can become resistant to antibiotic therapy, so can tumor cells to chemotherapy.

Even though combination chemotherapy has been shown to be effective in treating many diseases, utilizing and administering more than one agent also increases the potential for serious toxicities and complications. Utilizing cytoprotectant agents in these instances can lessen the organ dysfunction that can occur with therapies. These agents will be discussed later in this course.

One of the best sources for information on chemotherapy agents in the Oncology Nursing Society's (ONS) "Cancer Chemotherapy Course." This course is available nationally and is a comprehensive two-day course that details all aspects of cancer chemotherapy. Many institutions across the country are requiring all new and present oncology nurses to take this course. Although no certification or clinical practicum is attached to the course, an institution can prepare their own practicum experiences to add to the effectiveness of the course. In addition, once a participant successfully completes the course and post-test, ONS takes care of biannual updates for all participants. The ONS course is also a great opportunity to review in preparation for the oncology nursing certification (OCN) exam.

Provided within the course you are now taking is an overview of chemotherapy agents. Please remember there are new agents being discovered, developed, researched, and approved every year. This course will examine the classifications and will list agents (generic name) and toxicities associated with each classification. Keep in mind each drug has its own unique specificities and not all toxicities listed refer to each and every drug within a classification. Toxicities are detailed in the next section of this course.

The table below may not provide a listing of every antineoplastic chemotherapy agent due to continuing new developments. All drugs listed have FDA approval and are listed by generic names in this particular table to save space. Please refer to an oncologic pharmacology reference for drug-specific information, such as exact cellular phase in which action occurs, side effects, indications, dosing information, and administration guidelines. The appendix following the reference page of this course provides common trade names of the agents listed in the following table along with supportive agents. Two excellent references that should be available to all oncology nurses and nursing units are the Oncology Nursing Society's "Cancer Chemotherapy Guidelines and Recommendations for Practice" and the "2001 Oncology Nursing Drug Handbook" by Wilkes, Ingwersen, and Barton-Burke. The best resource is, of course, the manufacturer's package insert that can be obtained from the pharmacy admixing or dispensing the agent.