Streamlining outpatient cisplatin therapy to meet the challenges of today

Streamlining

Outpatient Cisplatin Therapy Challenges of Today

to Meet the

Margaret Hansen Frogge

REATER NUMBERS of cancer patients are now receiving cisplatin therapy in an outpaG tient setting than ever before. It is estimated that the vast majority of all chemotherapywill be administered in settings other than the hospital.’ Thesesettings include the outpatient clinic, office, day hospitals, and home. Studiesindicate that outpatient chemotherapycosts 20% to 30% less than inpatient therapy.2,3 Limited financial and human resourcesare forcing major changesin health care delivery patterns and decisions.4 The separation of clinical judgment from financial responsibility is coming to an end. Current challengesfocus on delivering quality care while maintaining the financial and social integrity of the patient and health care system.5 Outpatient administration of chemotherapywill meet the challengesof changing health care delivery becauseit is safe, effective, and provides social, physical, and financial benefits for the patient.6 Issues specifically related to outpatient cisplatin treatmenthave quickly shifted from questions of feasibility to questions of how we can provide cisplatin therapy in the most efficient, effective, and economical manner. Cisplatin is being used as primary and adjuvant therapy in many treatmentprotocols today.‘-’ ’ The increasing number of patients receiving cisplatin will continue to place additional demandson staff, space, and support services. Alternate methodsof delivery (ie, continuous infusion, intra-arterial catheters)are being investigatedand may even further facilitate safe and effective outpatient therapy.‘*,13 This article reviews approachesused in a number of outpatient settingsto streamlinethe delivery of quality care to patients receiving cisplatin therapy. PATIENT ENVIRONMENT

Outpatient cisplatin therapy is generally regarded as a lengthy treatment that can be administered from 90 minutes to sevenhours, depending on the protocol used. Whether the treatmentsetting is in an office, clinic, or home, efforts to insure privacy and quiet will enhancepatient tolerance of .%minars

treatment. A preferable setting is one outside the mainstream of office, home, or clinic activity. Most treatmentcentershave found that, in addition to cisplatin, there are many types of therapy that require a comfortable and relaxing environment (eg, amphotericin B infusions). Infusion chairs, recliners, and adjustable beds promote patient comfort. A wide variety of rooms and areas have been used for long-term treatment. Unused hospital rooms have been converted, specially designated infusion rooms designed, and traditional exam rooms in offices modified to accommodatecisplatin infusions. Severalpatients can be treatedin one room if the facility is large enough to accommodatethe infusion chairs while allowing adequatespacefor patients to walk to the bathroom easily. The aggressive hydration and diuresis regimens used with cisplatin therapy make it preferable to locate the treatment area near safety equipped bathrooms. In the home, it may be necessaryto have a bedside commodeavailable if the bathroom is not nearby. Most patients will have a family member or friend accompanythem to the treatment facility. It is important to provide a comfortable waiting area for these people. Some patients will want their family member to stay with them, whereas others may wish to be alone. PROFESSIONAL STAFF

Streamlining outpatient cisplatin therapy can be greatly enhancedby nurses with strong organizational skills, clinical expertise, and experience in administering outpatient chemotherapy. A skilled oncology nurse can organize the patient care process,provide completepatient assessmentsand patient and family teaching, administer the treatment protocol safely and effectively, and make sound From the Community Cancer Program, Riverside Medical Center, Kankakee, IL. Address reprint requests to Margaret Hansen Frogge, MS, RN, CNAA, Rt 3, Box 208, Kankakee, IL 60901. 6 1989 W.B. Saunders Company. 0749-2081l89lO502-1006$05..00/0

in Oncology Nursing, Vol 5, No 2, Suppl 1 (May), 1989: pp 21-28

21

22

MARGARET

clinical decisions in such areas as assessmentof effectiveness, early recognition and management of toxicities, and the implementation of approachesto promote patient comfort. Staff can gain clinical expertiseby working with experiencedoncology nursesin outpatient environments or by contacting a nearby facility to arrange an internship. It is also helpful to develop a network of outpatient chemotherapy nurses for support and exchange of ideas. Excellent patient education tools and treatment guidelines have been developed within such networks. The ideal nurse-to-patient ratio dependson the expertise of the nurse and whether the nurse has additional responsibilities in the office or clinic. An experienced oncology nurse, with the help of an assistant, should be able to handle several patients simultaneously. If additional work responsibilities are included, the nurse’s load may need to be limited. Part-time nurseswith flexible hours can be a valuable resourceon a limited work schedule. Some agencieshave found it helpful to stagger the starting times of patients’ therapies, others have implemented “cisplatin days,” and still others have scheduleddefinite times for the nurse to teach and conduct follow-up phone consultations. A well-coordinated schedule of long-term therapies greatly facilitates successful patient care. Some nurses use an objective scheduling system, where patients are classified as level 1, 2, or 3 according to acuity and nursing care intensity. This enables nurses to schedule a limited number of patients requiring more intensive care or teaching and counseling to receive cisplatin on a particular day, and allows staffing needs to be projected more accurately. PATIENT SELECTION

Appropriate patient selection is critical to the successof outpatient therapy. Factors to be considered when selecting the most effective setting for cisplatin therapy include clinical status, motivation, support, and insurance coverage. Before selecting the setting, these factors should be assessedand discussedwith the patient and his or her family. The patient’s family plays a significant role in the managementof outpatient cisplatin therapy, particularly before and after the treatment when encouragementand compliance are needed. The patient should be clinically strong enoughto withstand the demandsof the treatment regimen.

HANSEN

FROGGE

This includes having good respiratory, cardiac, and renal status to tolerate the fluid load without hospitalization. l4 The candidateshould have an acceptable performance status and be relatively asymptomatic. Effective control of drug-related nauseaand vomiting is another important clinical criterion. Some clinicians do not allow patients over 65 years of age to receive their initial treatment on an outpatient basis. If the initial treatment received in the hospital is well tolerated, the patient then becomes an outpatient for subsequent therapy. Becausemost of the preparation and posttreatment care of the outpatient occurs in the home, it is extremely important that both patient and family (or support group) understand, assume,and comply with the self-care protocol. Encouragement and emotional support from family or friends enable many patients to tolerate therapy and manage side effects more easily. Before therapy and immediately following therapy, a support person can help with the self-care protocols for preparation, antiemetic management,hydration, and rest. Insurance coverage for outpatient therapy is an important aspectof care. Most third-party insurers will cover outpatient chemotherapy;however, the few that do not can create a serious financial burden for the patient. Office staff can develop a protocol to determine the coverage a patient has with an insuring agency. In such a protocol, the insuring agent and patient should be questioned about the extent of coverage in the following areas: office cost of administration, supplies, drugs, lab tests, and support services (home care, day care, transportation). Insurance carriers are generally willing to review benefits and suggestappropriate billing procedures. In order to streamline the above assessments, someclinics have implemented patient assessment sheetsthat are completed by the physician, nurse, and office staff, and later become a part of the patient profile. The development of a protocol or processfor assessingthe patient’s potential to receive outpatient cisplatin therapy will avoid duplication of questions and work, and insure a complete assessment. PATIENT AND FAMILY-PARTNERS

IN CARE

Outpatient cisplatin therapy can be divided into three phases: pretreatment, active therapy, and posttreatment.The patient and family assumethe

STREAMLINING

OUTPATIENT

CISPLATIN

major role in the pretreatment and posttreatment phase. Therefore, it is imperative that both patient and family be well versed and competentto insure adequateself-care. Nursesare the key professionalgroup to provide complete education to the cancerpatient. I5 As oncologic care is administeredmore on an outpatient basis, it is important for nursesto negotiatepatient education as a componentof their work day. Some clinics and offices have the patient and family make an appointmentto meetwith the nursebefore therapy to review the entire outpatient process. Ideally, this appointmentis severaldays before the first treatment, so the patient and family may be more relaxed and receptive to education. Sessions usually last one hour. Group sessionsare an alternative that may make more efficient use of a nurse’s time. Other outpatient centers have developed formal teaching packetsthat include self-care guidelines, flow sheetsto documentteaching components, and teaching outlines that are standardized for their clinic (Table 1). It appearsthat clinic staffs that have worked together as a group (physicians, nurses, office staff) have been able to develop efficient and effective teaching programs. Whatever the teaching method selected, it is critical to keep the instructions simple, clear, and reinforced in written format for future reference. PREVENTION AND MANAGEMENT OF TOXICITIES

With more patients receiving cisplatin therapy, it will be helpful to develop protocols to prevent or Table 1. Taaching Flow Sheet Data

Initials

-

-

-

-

-

~

~

-

~ -

~

Pretreatment hydration Instruction sheet review Support person responsibilities Instruction sheet review Preparation-day of therapy Instruction sheet review Treatment process Hydration Antiemetic regimen Transportation Home care Instruction Posttreatment Hydration Antiemetic Diary Instruction

23

THERAPY

manage toxicities. Treatment times are compressed, thus forcing each patient to assume a greater role in the management of treatmentrelated toxicities. This section focuses on the major toxicities of cisplatin and managementof these effects during the pretreatment,active therapy, and posttreatment phases. Renal Function

Renal toxicity is a potential complication of cisplatin therapy that can be prevented or minimized with pretreatmentoral hydration, intravenous (IV) infusion of large volumes of fluid during therapy, and high-level oral hydration posttreatment.I6 For patients who cannot tolerate a high rate of fluid infusion or a large volume of fluid, hospitalization may be necessary.For patients with good pulmonary, cardiac, and renal function, the hydration protocols should be well tolerated. Higher dosesof cisplatin are associated with greater risk of nephrotoxicity. l7 Before each course of therapy, laboratory studies assessadequacyof renal function. A creatinine clearancelevel of more than 65 mUmin, and normal BUN, creatinine, and hematologic profiles are generally regarded as the standard criteria of acceptable renal function for cisplatin therapy. The day before therapy, patients are asked to drink at least ten to fifteen 8-0~ glassesof liquids, such as soup, juice, water, pop, gelatin, coffee, or electrolyte solution. To insure adequatehydration, it is helpful to have the patient record the liquids ingested (Table 2). This self-care diary is brought to the clinic by the patient, and hydration plans can be modified as needed. The day of therapy, patients are asked to drink three to four 8-0~ glasses of liquid before treatment. These should also be recorded in the selfcare diary. Some protocols require patients to drink a sodium- or electrolyte-containing drink within the four hours before therapy. Table 2. Chemotherapy Preparation Name:

sheet review

protocol sheet review

Liquid to drink the day before therapy: 8-02 glasses 3l288713ll 12Liquid to drink the morning of therapy 32l-

ten to fifteen 4S144-

5lo15-

MARGARET

24

During therapy, measuresto minimize nephrotoxicity include hydration, induction diuresis, and chloresis (0.9% sodium chloride infusions). Aggressive hydration, with or without induction diuresis, appears to decreasethe risk for cisplatin nephrotoxicity by decreasingurinary concentration of the drug, thereby decreasingrenal tubule exposure to the active drug and its metabolites.‘* Most hydration and diuresis protocols used with cisplatin therapy consist of one half to 3 L of 0.9% sodium chloride, plus electrolytes and mannitol or furosemide (Tables 3-5)” Standing orders for hydration protocols enable patient flow and more efficient therapy. Hydration is completed in one to six hours. If good oral hydration has been achieved, somephysicians administer 1 L of fluid over one to 1.5 hours and then discharge the patient.2oClinics using this shorter hydration protocol have not seenan increasedincidence of nephrotoxicity. Shorter, well-tolerated hydration times are a welcome alternative for most care centers. Someclinicians prefer not to use a diuretic in their protocols becauseof concernabout inadequatepretreatment hydration levels and extensive diuresis. A urine output of 100 mL/h is advised. The rate of cisplatin infusion may be a factor contributing to the risk of nephrotoxicity.21 Slow infusion of the drug, over 20 to 30 minutes, is recommended; however, the exact time over which the drug should be infused has not been clearly established. Flow sheets facilitate documentation of periodic assessmentsfor urine output and signs of fluid overload. Following therapy, patients are encouragedto continue aggressive hydration, since the highest levels of nonprotein-bound active cisplatin are excreted within 24 to 72 hours.22Most patients are heavily sedatedto control nauseaand vomiting and may require coaching to drink adequateamountsof fluid. Eight to ten 8-0~ glassesof fluid are desirTable 3. Hydration Regimen-Cisplatin

Table 4. Hydration and Diumsis Regimen-Cisplatin 100 mg/m’ IV

FROGGE

50 to

At-home instructions Ten to fifteen 8-02 glasses of liquid the day before and after chemotherapy Thiethylperazine maleate or metoclopramide 10 mg by mouth four times a day before therapy Regimen 500 mL D5W over 2 h before cisplatin therapy Mannitol 12.5 g in 500 mL normal saline, starting immediately after cisplatin therapy; and given over 2 h Cisplatin 50 to 100 mglm’ in 250 mL 3% saline given over 2 h Reprinted

with permission.‘s

able. Electrolyte-containing solution, soup, and cool liquids can be taken. The patient self-care diary servesas a useful reminder and record of oral intake. Nausea and Vomiting The emetogenicproperty of cisplatin can be effectively managedin most patients through the use of combination antiemetic regimens.23Y24 It is critical to useaggressiveantiemetic regimensfrom the outset of therapy. If a patient’s first experience with cisplatin therapy is poor, it may be more difficult to control nausea and vomiting for subsequent treatments. Chemotherapy-induced nausea and vomiting is a natural protective mechanismof the body. This natural protection is difficult to suppress; thus, multiple approachesare required to achievecontrol. Uncontrolled nauseaand vomiting can lead to inadequatehydration, electrolyte disturbances, malnutrition, and fatigue. Three types of nauseaand vomiting have been identified in patients receiving chemotherapy: acute, beginning within 24 hours; anticipatory, beginning before therapy; and delayed, persisting more than 24 hours after therapy. Each type is treated somewhat differently. In general, anti-

up to 60 mm/m’ IV Table 5. Hydration Regimen-Cisplatin

At-Home

HANSEN

IV up to 60 mg/m2

Instructions

Regimen Ten to fifteen 8-02 glasses of liquid the day before therapy 5% Dextrose in 0.45% sodium chloride + 20 mEq/L potassium chloride at 300 mUh, starting 0.5 h before cisplatin therapy; given over 3 to 5 h Cisplatin up to 80 mg/m* in 100 mL 0.8% sodium chloride given over 20 min Reprinted

with permission.”

One liter 0.9% sodium chloride given over 1 h before cisplatin therapy (0.45% sodium chloride may be substituted in patients with borderline cardiac status) Cisplatin up to 60 mg/m’ added to last 50 to 100 mL of above solution Reprinted

with permission.‘s

STREAMLINING

OUTPATIENT

CISPLATIN

emetic protocols involve multiple pharmacologic agentsand supportive interventions. Before therapy, many patients can benefit from prophylactic antiemetic therapy. As a result of anxiety or previous experiences,pretreatmentnausea and vomiting occur in about 60% of patients, usually after three or four courses have been received.25Lorazepam or diazepamcan be given the evening before therapy. A light, nutritious meal is encouraged.If the patient experiencesanticipatory nauseaand vomiting, the hints included in Table 6 may be helpful in addition to prophylactic antiemetic medication.26 During therapy, aggressiveantiemetic regimens are used to minimize acute nauseaand vomiting. Combinations of metoclopramide, dexamethasone, phenothiazines, butyrophenones,benzodiazepines, and glucocorticoids are most commonly used. Becausethere are multiple pathways in the brain and gastrointestinal (GI) tract through which nauseaand vomiting are induced, combinations of medications such as those listed in Tables 7 to 926 may be used. Each patient may responddifferently to a regimen. Therefore, it is important for the physician to select a number of antiemetic protocols for possible use. Multiple protocols enablethe

Table 6. Antlcipetory

Nausea and Vomiting

If you are vomiting or having nausea before your chemotherapy, it may be helpful to change your routine on the day of your treatment. Listed below are some steps that other patients have found helpful. Changing day or time of the appointment from morning to afternoon, or vice verse Changing the breakfast routine by eating a different type of meal or by eating in a different place Having someone else prepare meals Having a different family member or friend accompany you for your treatment-especially someone with whom you feel very comfortable Driving a new route Listening to a different radio station during the trip Listening to favorite tape Entering the clinic through a different door Arriving on time or close to scheduled appointment, but not too early Waiting in the hallway instead of in the waiting room Taking a portable TV or cassette player, for distraction Using relaxation techniques; deep breathing, visual imagery Trying medications to decrease anxiety (under physician’s direction only) Reprinted

with permission.2*

25

THERAPY

Table 7. Combination Antiemetic Regimens Drug

Dosage

2 mg/kg IV over 15 min, 30 min before, and every 2 h x 2 20 mg IV 30 min before 50 mg IV 30 min before 45 to 60 mg orally at home posttreatment

Metoclopramide Dexamethasone Diphenhydramine Flurazepam

Reprinted

with permission.*s

staff to have options in the approachesto management of this critical problem. At the outset, the goal of antiemetic control should be discussedwith the patient and family. A written guideline outlining the interventions to minimize nausea and vomiting is an invaluable aid. This guideline can be reviewed during the pretreatment teaching session.It is important that the patient and family know multiple options are available from which to choose, should the current methodnot provide adequatecontrol. Moderate sedation, defined as sedation to the point of arousal by physical stimulation, enhancespatient tolerance of therapy. An advantageof home therapy is that sedation can be maintained for a longer period of time. In outpatient situations, the family member who will be driving the patient home should encouragethe patient to continue sleeping as long as possible in the car and at home. Following therapy, it has been reported that delayed nauseaand vomiting occur in almost 60% of patients.*’ Delayed nausea and vomiting begin within 24 hours following therapy and can continue for three to six days. Altering the diet to include fresh, cool, light foods and providing a restful environment may help the patient. Antiemetic protocols listed in Table 1O26have been used to achieve control of delayed nausea and vomiting. Goodrnat~~~ has developed a patient diary that may be useful in evaluating the effectiveTable 8. Combination Antiemetic RegimenbCieplatin MS mglm2 Drug

Dosage

Metoclopramide Dexamethasone Lorazepam Reprinted

3 mg/kg IV or haloperidol 3 mg IV 30 min before and 90 min after 20 mg IV or methylprednisolone 250 to 500 mg IV 40 min before 1.5 mg/m2 35 min before

with permissionzs

26

MARGARET HANSEN FROGGE

Table 8. Combination Antiemetic Regimens-Cisplatin 75 me/m2

50 to

Table 10. Management of Delayed Nauses and Vomiting Day

Droperidol or haloperidol Dexamethasone

Dexamethasone

Drug

Dosage

1’

Metoclopremide

2

Dexamethasone Metoclopramide

2 to 2.5 mg IV 30 min before 8 mg orally the night before treatment; 4 mg orally every 4 h to 6 h on treatment day 10 mg IV 30 min before (over 5 min)

Over next two days, steroid dose is gradually tapered. Reprinted with permissions8

Dexamethasone 3 4

Dexamethasone Dexamethasone

0.5 mg/kg orally four times a day 8 mg orally twice a day 0.6 mg/kg orally three times a day 6 mg orally in the morning 4 mg orally in the evening 4 mg orally twice a day 4 mg orally in the morning

* First dose given day after cisplatin IV. Reprinted with permission.2e

ness of posttreatment regimens (see Fig 1). The nurse should place a follow-up telephonecall at 24 and 48 hours following therapy to assesspatient tolerance and provide counseling and suggestions as needed. Patients and family memberswelcome these calls. Additional Toxicities Ototoxicity is a potential adverse effect of cisplatin therapy that seemsto be related to cumulative dose, rate of infusion, and age.29*3o Symptoms of ototoxicity are generally reported by family or the patient. Infusing the drug slowly rather than via bolus injection has been suggestedas a measureto reduce ototoxicity. Audiometric evaluation of all patients receiving cisplatin is not routinely done. Clinicians should be aware of potential toxicity and periodically assessthe patient for signs of hearing loss. Neurotoxicity appearsto be related to cumulative high dosesof cisplatin in somepatients31 Peripheral neuropathy is the most common effect observed. Loss of taste, a myasthenic-like syndrome, postural hypotension, seizures, and ophthalmologic toxicities have been reported.32Neurologic toxicities appear to represent the major doselimiting toxicity of cisplatin. Patients should be observed for early signs of neuropathy, because therapy may need to be adjusted or stopped.33 When neuropathy is noted, the effects of cisplatin as an antitumor therapy must be considered and weighed. Electrolyte imbalances, specifically hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia, and inappropriate secretion of antidiuretic hormone have been noted with cisplatin therapy.34Standardmethodsfor replacementtherapy are implementedimmediately when abnormalities are verified through laboratory testing.

SUMMARY

Increasing numbersof patients are receiving full coursesof cisplatin therapy in such outpatient settings as clinics, offices, day hospitals, or home. Outpatient cisplatin therapy is administered safely and effectively in the ambulatory environment. Outpatient therapy is about one third the cost of inpatient therapy and offers the patient significant benefits in terms of work, illness perception, toleranceof side effects, and family strain. As more patients receive cisplatin on an outpatient basis, it is imperative that new strategiesbe developed to help streamline care to accommodatethe growing number of outpatients. This article reviews methodsusedin a variety of settings to provide quality care to larger numbers of patients. A critical factor to consider when developing new care methodsis how to maintain the fine balancebetween efficient, effective, economical, and quality care. Keeping that balance may necessitatea lot of trials and false starts. Developing a comfortable environment for cisplatin infusion is a matter of creativity. It is not necessaryto spendlarge sums of money to create an acceptable setting. Flow sheets, standardized teachingprotocols, patient information guides, patient diaries, and standardized hydration, antiemetic, and therapy protocols are just a few of the approachesthat have been usedto streamline care. Becoming involved in oncology nurse groups, networks, or continuing education programs are excellent avenues to meeting people who are all working on methods to streamline and provide quality care. The three elements of a successful outpatient program for the administration of cisplatin include having a comfortable setting, a well-organized, ex-

STREAMLINING OUTPATIENT CISPIATIN THERAPY

27

ChemotherapyTkatment Seven-DayDiary Name Medications to take after your chemotherapy Name

Time to take

How to take

1

--.-.I

Indicate below when you took your medicine and how you felt Date

Medication

Time

Degree of Nausea

Vomiting #of Times

1 = slight nausea 2 = severenausea, interferes with activities 0 = no nausea 3 = severenausea, intolerable Indicate how effective you feel these medications have been in preventing and managing your nausea: 0 not effective Cl very effective 0 moderately effective Put a check mark in the box which best describes how well you are able to eat and how you are feeling 3-6 days after your treatment. Day

Date

I throw up most everything and stay in bed most of the day

I feel some nauseaand have difficulty eating, but am eating and out

I am able to eat and go about my day as usual

of bed

Fig 1. A record that is kept by the patient can ba a useful tool to evaluate individual patient responses and the effactivene-w of posttherapy measures. (Reprinted with permission.-)

perienced staff, and appropriate patient selection. Patients are an excellent source of ideas for improving the care that they receive. A questionnaire or focus session with patients and families may yield valuable insights for improving care. The challenges of health care today will hopefully be met with methods that greatly benefit the patient. REFERENCES 1. Brown JK: Ambulatory services:The mainstay of nursing care. Oncol Nun Forum 12:57-59, 1985 2. Wodinsky HB, DeAngelis C, Rusthoven JJ, et al: Re-

evaluating the cost of outpatient cancer chemotherapy. Can Med Assoc J 137903906, 1987 3. Prager D: Chemotherapyin the physicians’ offtce. Penn Med 87:50-52, 1984 4. Suit HD: The scope of the problem of primary tumor control. Cancer 61:2141-2147, 1988 5. St011BA: Balancing cost and benefit in treatment of late cancer. Lancet 1:579-580, 1988 6. FroggeMH: Practical considerationsfor administration of cisplatin in the outpatient setting. Semin Oncol Nuts 3: 16-22, 1987 (suppl) 7. Giaccone G, Donadio M, Ferrati P, et al: Cisplatin and etoposide in chemotherapy-refractoryadvanced breast cancer. Tumori 74:191-193, 1988

28 8. Shepherd FA, Evans WK, Feld R, et al: Adjuvant chemotherapyfollowing surgical resectionfor small-cell carcinoma of the lung. J Clin Oncol 6:832-838, 1988 9. Fisoli F, Veronesi A, Adrizzoni A, et al: Cisplatin and etoposideas second-linetherapy in patients with small cell lung cancer. Cancer Invest 61-5, 1988 10. Raghavan D, PearsonD, Duval B, et al: Neoadjuvant intravenouscisplatin for T2-4NxMo bladder cancer. Prog Clin Biol Res 260:561-570, 1988 11. Ha&worth JD, Dial TW, Greco FA: Curative combination chemotherapyfor patients with advancedpoorly differentiated carcinoma of unknown primary site. Am J Clin Oncol 11:138-145, 1988 12. PosnerMR, Ferrari L, Belliveau JF, et al: A phaseI trial of continuouscisplatin. Cancer 59:15-18, 1987 13. Rettenmaier MA, Moran MF, Ramsinghani NF, et al: Treatment of advanced and recurrent squamouscarcinoma of the uterine cervix with constantintraarterial infusion of cisplatin. Cancer 61:1301-1303, 1988 14. Alberts DS, DesserRK, Frogge MH: Outpatient administration of Platinol(cisplatin for injection). Indiana, BristolMyers Oncology Division, 1987 15. Welch-McCaffrey D: Evolving patient education needs in cancer. Oncol Nurs Forum 12:62-66, 1985 16. Finley RS, Former CL, Grove WR: Cisplatin nephrotoxicity: A summary of preventive interventions. Drug Intel1 Clin Pharm 19:362-367, 1985 17. Comis RL: Cisplatin nephrotoxicity: The effect of dose, scheduleand hydration scheme,in PrestaykoAW, Crooke ST, Carter SK (eds): Cisplatin, Current Status and New Developments. Orlando, FL, Academic, 1980, pp 485-494 18. Hayes D, Cvitkovic E, Golbey R, et al: High dose cisplatinumdiaminedichloride amelioration of renal toxicity by mannitol diuresis. Cancer 39:1372-1381, 1977 19. Alberts DS, Desser RK, Frogge MH, et al: Module 5: Maintenance of renal function with hydration and diuresis, in Platinol (Cisplatin for Injection): Outpatient and Office Administration. Evansville, IN, Bristol-Myers Oncology Division, 1987. 20. Brock J, Alberts DS: Safe, rapid administration of cisplatin in the outpatient clinic. CancerTreat Rep 70:1409-1414, 1986 21. Patton T, Himmelstein K, Belt R, et al: Plasma levels and urinary excretion of filterable platinum speciesfollowing

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bolus injection and IV infusion of cis-dichlorodiamineplatinum (II) in man. Cancer Treat Rep 621359-1362, 1978 22. Evans WE, Yee GC, Crom WR, et al: Clinical pharmacology of bleomycin and cisplatin. Drug Intel1 Clin Pharm 62:448-458, 1982 23. Kris MC, Gralla RJ, Tyson LB, et al: Improved control of cisplatin inducedemesiswith high-dosemetoclopramideand with combinationsof metoclopramide,dexamethasone,and diphenhydramine.Cancer 55:527-534, 1985 24. Onsrud M, Moxnes A, Sollien A, et al: High-dose versus low-dose metoclopramide in the prevention of cisplatininducedemesis.A randomizedcrossoverstudy in patients with ovarian carcinoma. Cancer 61:2429-2432, 1988 25. Fetting TH, Wolcox PM, Iwata BA, et al: Anticipatory nauseaand vomiting in an ambulatory medical oncology population. Cancer Treat Rep 67:1093-1098, 1983 26. Alberts DS, Desser RK, Frogge MH, et al: Module 4: Preventionand managementof nauseaand vomiting, in Platinol (Cisplatin for Injection): Outpatient and Office Administration. Evansville, IN, Bristol-Myers Oncology Division, 1987 27. Strum S, McDermed J, Abrahano-Umali R, et al: Managementof cisplatin (DDP)-induced delayed onset nauseaand vomiting: Preliminaty resultswith two drug regimens. Pmc Am Sot Clin Oncol4:263, 1985 (abstr) 28. GoodmanMS: Managementof nauseaand vomiting induced by outpatient cisplatin (Platinol) therapy. Semin Oncol Nurs 3:23-35, 1987 (suppl) 29. Fleming SM, PetersGM, Weaver AW, et al: Ototoxicity associatedwith cis-platinum in three chemotherapymulti-drug regimens. Cancer 51:610-613, 1983 30. Vermorken HB, Kapteijn TS, Hart AAM, et al: Ototoxicity of cisdiamminedichloroplatinum (III): Influence of dose, scheduleand mode of administration. Eur J Cancer Clin Oncol 19:53-58, 1983 31. Legha SS, Dimery IW: High-dose administration without hypertonic saline: Observationof disabling neurotoxicity. J Clin Oncol 3:1373-1378, 1985 32. Thompson SW, Davis LE, Komfeld M, et al: Cisplatin neuropathy: Clinical, electrophysiologic, morphologic, and toxicologic studies. Cancer 54:1269-1275, 1984 33. Ostchega Y, Donohue M, Fox N: High-dose cisplatin related peripheral neuropathy. Cancer Nurs 11:23-32, 1988 34. Perez E, Hutchinson F, Gandara D, et al: Cisplatininduced salt-wasting neuropathy: Clinical and laboratory parameters. Proc Am Sot Clin Oncol 6:265, 1987 (abstr)