*Health Canada approved indication

cross-sensitivity with other alkylating agents.1

combination with other antineoplastics. Occurring most frequently are bladder, myeloproliferative and

lymphoproliferative malignancies. Secondary malignancies are most common in patients treated initially for

myeloproliferative or lymphoproliferative diseases or for non-malignant conditions with immune pathology. Urinary

bladder malignancies are most common in patients who experienced hemorrhagic cystitis.

be used by patients (both male and female) during and at least four months after treatment.1

chemotherapy are the main factors contributing to ovarian failure.14 For example, treatment with cyclophosphamide,

methotrexate and fluorouracil for six months results in permanent ovarian failure in 70 percent of women over 40

years of age and in 40 percent of younger women. The median time to onset of ovarian failure is shorter in older

women than in younger women (2-4 months vs. 6-16 months), and ovarian failure is less likely to be reversible in

older women (in about 10 percent vs. up to 50 percent). The rate of permanent ovarian failure is lower with regimens

of doxorubicin and cyclophosphamide than with cyclophosphamide, methotrexate and fluorouracil.

disease.7

in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for

a serious disease for which safer drugs cannot be used or are ineffective).

milk.1

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 3 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

The table includes adverse events that presented during drug treatment but may not necessarily have a causal

relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event

rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they

were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be

clinically important.15

I = immediate (onset in hours to days); E = early (days to weeks);

D = delayed (weeks to months); L = late (months to years)

allergy/immunology anaphylactic reaction16 (<1%) I

nasal congestion when IV doses are administered too rapidly (large

doses via 30-60 minute infusion);16 patients experience runny eyes,

rhinorrhea, sinus congestion, and sneezing immediately after

infusion.16 (1-10%)

I

anemia E

methemoglobinemia with bone marrow transplant (BMT) doses16 E

E

blood/bone marrow/

febrile neutropenia

thrombocytopenia E

E

coagulation hypoprothrombinemia, risk of bleeding (very rare) E

constitutional symptoms asthenia or sweating (0.1-1%) E

dizziness16 (<1%) E

alopecia8,16 (40-60%); begins 3-6 weeks after start of therapy E

facial flushing following IV administration3,16 (1-10%) I

hyperpigmentation (skin and nails)3,16 (<1%) E

rash, hives or itching3,16 (1-5%) I

redness, swelling, or pain at injection site3,16 I

dermatology/skin

toxic epidermal necrolysis16 (<1%) E

endocrine hyperglycemia3 E

anorexia (33%) E

diarrhea16 (>10%) E

hemorrhagic colitis16 (<1%) E

mucositis16 (>10%) E

gastrointestinal

myxedema or sore lips3 (0.1-11%) E

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 4 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

I = immediate (onset in hours to days); E = early (days to weeks);

D = delayed (weeks to months); L = late (months to years)

I

stomatitis3,16 (>10%) E

hepatic hepatotoxicity16 (<1%) E

jaundice16 (<1%) E

hyperkalemia, usually in context of tumour lysis16 (<1%) E

hyperuricemia with high-dose and/or long-term therapy16 (<1%) E

metabolic/laboratory

syndrome of inappropriate antidiuretic hormone (SIADH) causing

hyponatremia

E

pain headache3,16 (1-10%) I

interstitial pulmonary fibrosis, with high-dose and/or long-term

therapy16 (<1%)

pulmonary D

pneumonitis, with high-dose and/or long-term therapy16 (<1%) E

non-hemorrhagic cystitis7 E

E

renal tubular necrosis16 (1-5%) E

renal/genitourinary

hemorrhagic ureteritis (<1%) E

secondary malignancy urinary bladder, myeloproliferative or lymphoproliferative

malignancies16 (<1%)

L

sexual/reproductive

function

interferes with oogenesis and spermatogenesis16 (>10%); may be

irreversible in some patients; gonadal suppression (amenorrhea)3

E

syndromes syndrome of inappropriate antidiuretic hormone (SIADH) secretion

with high-dose and/or long-term therapy3,16 (1-5%)

E

Adapted from standard reference1,12 unless specified otherwise.

mg/kg daily or 120-270 mg/kg over a few days.12 Other risk factors for developing cardiac toxicity include previous

chest or mediastinal radiotherapy, anthracycline administration, concomitant administration of chemotherapy drugs

which are not normally considered cardiotoxic, especially carmustine, cytarabine and 6-thioguanine,5 and by the

presence of left ventricular dysfunction (ejection fraction less than 50%).19 The mechanism may involve direct injury

to the endothelium by phosphoramide mustard, an active metabolite of cyclophosphamide.19,20Unlike anthracyclines,

cyclophosphamide-induced cardiotoxicity does not appear to be cumulative.5,19,21 In contrast to anthracyclineinduced

cardiomyopathy which occurs months to years after cumulative doses of anthracyclines,

cyclophosphamide-induced cardiotoxicity occurs much earlier.20 Toxicity has ranged from minor, transient ECG

changes and asymptomatic elevation of cardiac enzymes at a total dose of 100 mg/kg to fatal myocarditis and

myocardial necrosis at total doses ranging upwards from 144 mg/kg delivered over 4 days.5 Clinical signs include

dyspnea, tachypnea, fluid retention, increased systemic venous pressure and shock.22 Patients may experience

heart failure, arrhythmias, irreversible cardiomyopathy, pericarditis or death as a result of cardiotoxicity.22 Treatment

is supportive.5

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 5 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

cyclophosphamide therapy.7,12 Other risk factors for developing hemorrhagic cystitis include rate of infusion, and rate

of metabolism of cyclophosphamide, as well as the hydration status, urine output, frequency of urination, and

concurrent exposure to other urotoxic drugs or genitourinary radiotherapy.23 The mechanism may involve direct

injury to the urothelium by acrolein, an active metabolite of cyclophosphamide.11 Hemorrhagic cystitis can develop

within a few hours or be delayed several weeks.3 Clinical diagnosis includes non-specific symptoms such as

hematuria, dysuria, urgency and increased frequency of urination and can be confirmed using cystoscopy.23 Severe

hemorrhagic cystitis can lead to constriction of the bladder, anemia, recurrent urinary tract infection, bladder

perforation, renal failure and death.23 Long term complications include bladder fibrosis and contraction, urinary reflux

and transitional cell bladder tumours. Non-hemorrhagic cystitis, edema of the bladder and suburethral bleeding can

also occur.7

at least 2 L/day), to void frequently, and to avoid taking the drug at night.16 Patients should be well hydrated before

and for 24-72 hours following treatment.23 As well, cyclophosphamide should be administered as early in the day as

possible to decrease the amount of drug remaining in the bladder overnight.3 With large IV doses, IV hydration is

usually recommended.16 The use of mesna and/or continuous bladder irrigation is rarely needed for doses <2g/m2.16

However, mesna has been used in patients receiving cyclophosphamide for immunologically mediated disorders

(e.g., Wegener’s granulomatosis, systemic lupus erythromatosus, dermatomyositis, polyarteritis).12 Further

measures to reduce the incidence of cystitis include catheter bladder drainage, bladder irrigation, intravenous

hydration with diuresis, hyperhydration, and the administration of mesna. Hyperhydration is generally not

recommended as it places the patient at risk for fluid overload and electrolyte imbalance, particularly given the

antidiuretic effect of cyclophosphamide.23 Diuretics may be indicated if urine production declines to <100 mL/m2/h. It

appears that mesna and hyperhydration are equally effective in preventing cyclophosphamide-induced cystitis in the

BMT population.

increased and the platelet count should be maintained at >50 000/mm3 to minimize the extent of bleeding. There is

several treatment options currently advocated, depending on the severity of bleeding.

Treatment of early cystitis24:

at a rate of 3.0 L/m2 per 24-hour period. Depending on the patient’s electrolyte status, KCl and MgS04 are

generally added to the fluid at concentrations 20-40 mEq/L and 2-4 g/L respectively. Patients who have

visible clots in the urine, or have bladder spasms should receive continuous bladder irrigation. Treatment is

generally continued for 48 hours after the urine returns to normal colour and the symptoms have resolved.

prepared by pharmacy as a 1% solution for intravesical administration. This is instilled at a rate of 300-1000

mL/hour and the rate is adjusted to maintain clear pink drainage. Responses to Alum are improved

following removal of clots in the bladder using either cystoscopy or irrigation prior to therapy. As Alum

contains significant amounts of aluminum, aluminum levels should be taken in patients with renal

impairment, or in patients requiring prolonged therapy.

and cause local vasoconstriction. The dose is generally 0.8-1.0 mg/dL in 50 mL NS (400-500 mcg) instilled

into the bladder; clamp catheter and allow solution to dwell for 60 minutes; repeat every six hours until

response.24 Like Alum, this therapy works best when the bladder is evacuated of clots before starting.

Patients who respond will do so by 5-7 days. Carboprost can cause intense bladder spasm and this can be

a major problem. Therapy with oxybutinin, Belladonna and opium suppositories or systemic narcotic

analgesics may be necessary. In rare cases hemorrhagic cystitis is resistant to the above treatments and

bladder fulguration with formalin or other chemicals is needed.

Treatment of late onset cystitis24:

Many of these cases are due to secondary viral infection or bacterial infection of the injured mucosa. Culture for

bacterial pathogens, cytomegalovirus (CMV) and adenovirus should be done before starting therapy. Primary

therapy is hyperhydration possibly with bladder irrigation. Patient may be need to be treated if pathogen is found i.e.

ganciclovir or foscarnet for CMV, ribaviron for adenovirus, antibiotics for bacterial infections.

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 6 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

candida) are frequently suppressed in patients receiving cyclophosphamide.12

acute renal failure.25 It is most likely with highly proliferative tumours of massive burden, such as leukemias, highgrade

lymphomas and myeloproliferative diseases. The risk may be increased in patients with preexisting renal

dysfunction, especially ureteral obstruction. Suggested prophylactic treatment for high-risk patients24:

salicylates)

Urine should be alkalinized only if the uric acid level is elevated, using sodium bicarbonate IV or PO titrated to

maintain urine pH > 7. Rasburicase (Fasturtec®) is a novel uricolytic agent that catalyzes the oxidation of uric acid

to a water-soluble metabolite, removing the need for alkalinization of the urine.26 It may be used for treatment or

prophylaxis of hyperuricemia, 0.2 mg/kg IV daily for up to 7 days; however, its place in therapy has not yet been

established.

periods. Other risk factors include exposure to other drugs with pulmonary toxicities and pulmonary radiotherapy.

The mechanism may involve direct injury to the pulmonary epithelium by cyclophosphamide metabolites.27 In some

cases discontinuation of the drug and initiating corticosteroid therapy fails to reverse this condition, which can be

fatal. Signs and symptoms typically include tachycardia, dyspnea, fever, non-productive cough, basilar crepitant

rales, interstitial bilateral infiltrates on chest x-ray, hypoxemia and ventilation/perfusion dysfunction. Interstitial

pneumonitis has also been reported in patients receiving cyclophosphamide. The drug should be stopped at the first

sign of pulmonary toxicity; all other possible causes of pneumonitis should be ruled out.

associated with rapid injection of cyclophosphamide.28-30 This reaction may be caused by a mucosal inflammatory

response or possibly a cholinergic mechanism.31 If troublesome for the patient, several interventions have been

used31: the slowing down of the infusion rate or giving as an intermittent infusion rather than as an IV bolus, the use

of analgesics, decongestants, antihistamines, intranasal beclomethasone, or intranasal ipratropium.

rare side effect. While often called radiation recall reactions, the timing of the radiation may be before, concurrent

with, or even after the administration of the cyclophosphamide. Recurrent injury to a previously radiated site may

occur weeks to months following the radiation.

resulting in hyponatremia, dizziness, confusion or agitation, unusual tiredness or weakness. This syndrome is more

common with doses >50 mg/kg and may be aggravated by administration of large volumes of fluids to prevent

hemorrhagic cystitis.9 The condition is self-limiting although diuretic therapy may be helpful in the situation when the

patient has stopped urinating (especially if this occurs during the first 24 hours of cyclophosphamide therapy).

Susceptible patients should be monitored for cardiac decompensation. If weight gain is excessive (1.5-2 kg) during

hydration, the volume of IV fluid should be reduced.

frequently reported neoplasms are urinary bladder cancer, non-lymphocytic leukemia and non-Hodgkin's lymphoma.

Urinary bladder malignancies generally have occurred in patients who previously had hemorrhagic cystitis.7

mg/kg has been associated with water retention and dilutional hyponatremia.9,12 Children may be especially

susceptible. The mechanism is related to direct injury to the distal renal tubules and collecting ducts by

cyclophosphamide metabolites. Symptoms include decreased urine flow, decreased serum osmolarity and sodium

and increased urine osmolarity. These can occur 4 to 12 hours after cyclophosphamide and resolve within 20 to 24

hours after therapy.

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 7 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

allopurinol delayed, moderate;

increased

myelosuppressive effects

of cyclophosphamide is

possible

unknown frequent monitoring with a

complete blood count may

be required

amiodarone32 increased risk of

pulmonary fibrosis

unknown, possibly additive

effect

avoid combination if

possible; otherwise

increase monitoring

chloramphenicol delayed, moderate;

decrease or delay in

activation of

cyclophosphamide

inhibition (weak) of the

CYP2C8/9 and CYP3A4

enzymes by

chloramphenicol16,33

standard monitoring

procedures for both drugs

ciprofloxacin34 delayed, moderate;

decreased antimicrobial

effect of quinolone

antibiotics is possible

decreased quinolone

absorption by altering the

intestinal mucosa

ciprofloxacin can be used

as a prophylactic antibiotic

in cyclophosphamide

based regimens.35

consider monitoring

ciprofloxacin therapy.

corticosteroids decreased or increased

effect of

cyclophosphamide

induction (weak) of the

CYP3A4 enzyme by

corticosteroids16,36-38

clinical significance of this

interaction is unlikely

based on evidence

available; observe for

altered effect of

cyclophosphamide.

digoxin delayed, moderate;

reduced serum levels of

digoxin is suspected

drug-induced alterations of

the intestinal mucosa may

be involved

monitoring for reduced

digoxin effect

grapefruit juice39 delayed, moderate;

decreased or delayed

activation of

cyclophosphamide

inhibition (moderate) of the

CYP3A4 enzyme16,40 by

grapefruit juice

avoid grapefruit juice for

48 hours before and on

day of dose

hydrochlorthiazide delayed, moderate;

prolonged leucopenia is

possible

unknown avoid concurrent use;

consider alternative

antihypertensive therapy

indapamide delayed, moderate;

prolonged leucopenia is

possible

unknown avoid concurrent use;

consider alternative

antihypertensive therapy

indomethacin7 4 cases of severe

pulmonary edema and

acute life-threatening

water intoxication

unknown avoid concurrent use

phenytoin10, phenobarbital,

rifampin and other drugs

which induce CYP2B641

increased rate at which

cyclophosphamide is

converted to active and

toxic metabolites and

possibly to inactive

metabolites

induction (strong) of the

CYP2B6 enyzme16,41 by

phenytoin, phenobarbital

and rifampin.

clinical significance of this

interaction is unknown;

observe for altered effect

of cyclophosphamide

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 8 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

succinylcholine rapid, moderate;

prolonged neuromuscular

blockade produced by

succinylcholine is probable

cyclophosphamide inhibits

plasma cholinesterase

resulting in decreased

metabolism of

succinylcholine

consider reducing

succinylcholine based on

measured plasma

cholinesterase levels

warfarin delayed, moderate;

increased anticoagulant

effect of warfarin

suspected

inhibition of warfarin

metabolism, or clotting

factor synthesis

monitoring coagulation

parameters during and

after chemotherapy; adjust

warfarin dose as needed

Adapted from standard reference34 unless specified otherwise.

vials of 1000 mg and 2000 mg. Contains no preservative. Protect from light.

mg and 2000 mg vials. Contains no preservative. Protect from light.

diluent and for 2 g vial add 100 mL diluent. Add the diluent to the vial and shake it vigorously to dissolve. If the

powder fails to dissolve immediately and completely, let the vial stand for a few minutes. Heat should not be used.

take several hours for complete dissolution.42 For 200 mg vial add 10 mL NS, for 500 mg vial add 25 mL, for 1000

mg add 50 mL and for 2000 mg add 100 mL.

the refrigerator1

Sodium Lactate Injection and NS.43 Diluted solutions are chemically and physically stable for 24 hours at room

temperature or for 6 days in the refrigerator.44,45

temperature, or 72 hours refrigerated.

microbiological growth should be considered when assigning expiration periods.

cimetidine, cisplatin, cladribine, dexamethasone, diphenhydramine, doxorubicin, liposomal doxorubicin, droperidol,

etoposide, fludarabine, fluorouracil, furosemide, gemcitabine, granisetron, heparin, hydromorphone, idarubicin,

leucovorin, lorazepam, melphalan, methotrexate, methylprednisolone, metoclopramide, mitomycin, ondansetron,

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 9 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

paclitaxel, prochlorperazine, promethazine, propofol, ranitidine, sodium bicarbonate, thiotepa, vinblastine, vincristine,

vinorelbine.

The following are compatible in the same infusion solution: cisplatin with etoposide, fluorouracil, mesna,

methotrexate, mitoxantrone and ondansetron.

The following are compatible in the same syringe: furosemide, heparin, leucovorin, metoclopramide.

Subcutaneous no information found

Intramuscular has been used

Intraperitoneal has been used but not recommended due to need for

metabolic activation12

Intrapleural has been used but not recommended due to need for

metabolic activation12

Intrathecal no information found; metabolic activation required12

Intra-arterial no information found

Intravesical no information found

Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease,

response and concomitant therapy. Guidelines for dosing also include consideration of absolute neutrophil count.

Dosage may be reduced, delayed or discontinued in patients with bone marrow depression due to cytotoxic/radiation

therapy or with other toxicities.

Cycle Length:

Round dose to the nearest 25 mg. The manufacturer recommends that the drug be taken on an empty stomach, but

states it may be taken with food to decrease GI upset6

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 10 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

Cycle Length:

Oral liquid preparations of Cytoxan® may be prepared by dissolving the cyclophosphamide powder for injection or

the lyophilized powder for injection in Aromatic Elixir, NF.1 Solution stable in amber glass containers for 14 days,

refridgerated.12

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 11 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

chemotherapy35,65-71

available, refer to Appendix 6 "Dosage Modification for Myelosuppression"

>50-10 100%

<10 75%

Calculated creatinine clearance = N* x (140 - Age) x weight

Serum Creatinine in μmol/L

* For males N = 1.23; for females N = 1.04

hemodialysis: ½ dose has been suggested72

there have been 2 case reports of giving high-dose cyclophosphamide with

continuous bladder irrigation +/- mesna.73,74 Hemodialysis (duration 6 h) was

performed 6 h73 and 14 h74 after cyclophosphamide infusion. Dialysis should not

be started sooner then 12 h after cyclophosphamide infusion.75

chronic ambulatory peritoneal dialysis (CAPD): no data72

continuous arteriovenous or venovenous hemofiltration (CAVH): dose for GFR

10-5072

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 12 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

Cycle Length:

Oral: daily: 50-300 mg/m2

Intravenous: 3-4 weeks76: 250-1800 mg/m2 for one dose on day 1, day 2, day 3 and

day 4

3-4 weeks77: up to 2000-3000 mg/m2 for one dose on day 1

1. Bristol-Myers Squibb Canada. Cyclophosphamide product monograph. Montreal, Canada; 2004.

2. National Institute for Occupational Safety and Health (NIOSH). Preventing occupational exposures to antineoplastic and other

hazardous drugs in healthcare settings. Cincinnati, Ohio: NIOSH - Publications Dissemination; 25 Mach 2004. p. 71-83.

3. Cyclophosphamide. USP DI. Volume 1. Drug information for the health care professional. 2Oth ed. Englewood, Colorado:

Micromedex, Inc.; 2002.

4. Crom WR, Glynn-Barnhart AM, Rodman JH, et al. Pharmacokinetics of Anticancer Drugs in Children. Clin Pharmacokinet

1987;12:179-82.

5. Perry MC. The Chemotherapy Source Book. Baltimore: Williams & Wilkins; 1992. p. 286-9.

6. Kinda Karra. Personal Communication. Associate, Medical Information and Drug Safety, Bristol-Myers Squibb Canada 2005.

7. Repchinsky C, BSP. Compendium of Pharmaceuticals and Specialties; 2004. p. 1610-3.

8. Balis F, Holcenberg JS, Bleyer WA. Clinical Pharmacokinetics of Commonly Used Anticancer Drugs. Clin Pharmacokinet

1983;8: 202-232.

9. Dorr RT, Von-Hoff DD. Drug monographs. In: Dorr R, Von-Hoff D, editors. Cancer chemotherapy handbook. 2nd ed. Norwalk,

Conneticut: Appleton and Lange; 1994. p. 319-32.

10. de Jonge ME, Huitema ADR, van Dam SM, et al. Significant induction of cyclophosphamide and thiotepa metabolism by

phenytoin. Cancer Chemother Pharmacol 2004;55:507-10.

11. Miller LJ, Chandler SW, Ippoliti CM. Treatment of cyclophosphamide-induced hemorrhagic cystitis with prostaglandins. Annals

of Pharmacotherapy 1994;28(5):590-4.

12. McEvoy GK. AHFS 2004 Drug Information. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.; 2004.

p. 948-52.

13. Cyclophosphamide. USP DI. Volume 1. Drug information for the health care professional. 2Oth ed. Englewood, Colorado:

Micromedex, Inc.; 2000. p. 1155-61.

14. Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. NEJM 2001;344(26):1997-2008.

15. Tamara Shenkier. Personal communication. Medical Oncologist, BC Cancer Agency Vancouver Centre 2005.

16. Cyclophosphamide: Drug Information. In: Rose BD, editor. UpToDate. Wellesley, MA,: UpToDate; 2005.

17. B.C. Cancer Agency Provincial Systemic Therapy Program. Provincial Systemic Therapy Program Policy III-20: Prevention and

management of extravasation of chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 1 February 2004.

18. B.C. Cancer Agency. SCNAUSEA Protocol Summary. Vancouver, British Columbia: BC Cancer Agency; May 1999.

19. Taniguch I. Clinical Significance of Cyclophosphamide-induced Cardiotoxicity. Intern Med 2005;44(No. 2):89-90.

20. Kamezaki K, Fukuda T, Makino S, et al. Cyclophosphamide-induced Cardiomyopathy in a Patient with Seminoma and a History

of Mediastinal Irradiation. Intern Med 2005;44(No 2):120-3.

21. Chanan-Khan A, Srinivasan S, Czuczman M. Prevention and Management of Cardiotoxicity from Antineoplastic Therapy. J

Support Oncol 2004;2:251-66.

22. Angelucci E, Mariotti E, Lucarelli G, et al. Sudden cardiac tamponade after chemotherapy for marrow transplantation in

thalassaemia. Lancet 1992;339(8788):287-9.

23. West NJ. Prevention and treatment of hemorrhagic cystitis. Pharmacotherapy 1997;17(4):696-706.

24. Leukemia/Bone Marrow Transplant Program of British Columbia. Leukemia/BMT Manual; 2003. p. 76-7.

25. DeVita VT, Hellman S, Rosenberg SA. Cancer Principles & Practice of Oncology. 6th ed. Philadelphia: Lippincott Williams &

Wilkins; 2001.

26. Sanofi-Synthelabo. Rasburicase product information package. Markham, Ontario; 2004.

27. Segura A, Yuste A, Cercos A, et al. Pulmonary fibrosis induced by cyclophosphamide. Annals of Pharmacotherapy 2001;35(7-

8):894-7.

28. Kosirog-Glowacki JL, Bressler LR. Cyclophosphamide-induced facial discomfort. Annals of Pharmacotherapy 1994;28(2):197-

9.

29. Arena PJ. Oropharyngeal sensation associated with rapid intravenous administration of cyclophosphamide (NSC-26271).

Cancer Chemotherapy Reports - Part 1 1972;56(6):779-80.

30. Silberstein PT, Vercellotti GM. Facial burning from cyclophosphamide. Cancer Treatment Reports 1984;68(7-8):1057.

31. Lo K, Aulakh AK, Gingerich KS, et al. Cyclophosphamide-induced nasopharyngeal discomfort (wasabi nose): a report of two

cases. 2002;J Oncol Pharm Practice(8):131-4.

32. Bhagat R, Sporn TA, Long GD, et al. Amiodarone and cyclophosphamide: potential for enhanced lung toxicity. Bone Marrow

Transplantation 2001;27(10):1109-11.

33. Chloramphenicol: Drug Information. In: Rose BD, editor. UpToDate. Wellesley, MA,: UpToDate; 2005.

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 13 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

34. Tatro D, editor. Drug Interactions Facts on Disc. St. Louis: Facts and Comparisons; 2004.

35. BC Cancer Agency Breast Tumour Group. BCCA protocol summary for adjuvant thearpy for breast cancer using

cyclophosphamide, epirubicin and fluorouracil (BRAJCEF). Vancouver: BC Cancer Agency; 2002.

36. Dexamethasone: Drug Information. In: Rose BD, editor. UpToDate. Wellesley, MA.: UpToDate; 2005.

37. Prednisolone: Drug Information. In: Rose BD, editor. UpToDate. Wellesley, MA,: UpToDate; 2005.

38. Prednisone: Drug Information. In: Rose BD, editor. UpToDate. Wellesley, MA,: UpToDate; 2005.

39. Repchinsky C, BSP. Compendium of Pharmaceuticals and Specialties; 2005. p. L74.

40. Lexi-Comp Inc. CYP3A4 Substrates/CYP3A4 Inhibitors (Moderate). In: Rose BD, editor. UpToDate. Wellesley, MA: UpToDate;

2005.

41. Lexi-Comp Inc. CYP2B6 Substrates/CYP2B6 Inducers (Strong). In: Rose BD, editor. UpToDate. Wellesley, MA.: UpToDate;

2005.

42. Paul Agro, BScPhm. Personal Communication. Agro Health Associates Inc 2005.

43. Mario de Lemos. Non-lyophilized cyclophosphamide. Systemic Therapy Update 2005;Volumn 8, number 2.

44. Nicole Hojm. Personal communication. Medical Information Manager, Bristol-Myers Squbb Canada;November 26 2004.

45. Kinda Karra. Personal communication. Medical Information Officer, Bristol-Myers Squbb Canada;November 26 2004.

46. Trissel L. Handbook on Injectable Drugs. 13th ed. Houston: American Society of Health-System Pharmacists; 2005.

47. BC Cancer Agency Lymphoma Tumour Group. BCCA protocol summary for lymphoma palliative chemotherapy. Vancouver:

BC Cancer Agency; 2002.

48. BC Cancer Agency Breast Tumour Group. BCCA Protocol summary for adjuvant therapy for breast cancer using

cyclophosphamide, doxorubicin and fluorouracil (BRAJCAF). Vancouver: BC Cancer Agency; 2001.

49. BC Cancer Agency Breast Tumour Group. BCCA Protocol summary for adjuvant therapy for breast cancer using doxorubicin

and cyclophosphamide (BRAJAC). Vancouver: BC Cancer Agency; 2001.

50. BC Cancer Agency Lung Tumour Group. BCCA Protocol summary for treatment of extensive small cell lung cancer (SCLC)

with cyclophosphamide, doxorubicin and vincristine (CAV) (LUCAV). Vancouver: BC Cancer Agency; 2002.

51. BC Cancer Agency Breast Tumour Group. BCCA Protocol summary for adjuvant therapy for premenopausal high risk breast

cancer using cyclophosphamide, methotrexate and fluorouracil (BRAJCMF). Vancouver: BC Cancer Agency; 1999.

52. BC Cancer Agency Lung Tumour Group. BCCA Protocol summary for treatment of extensive small cell lung cancer with

cyclophosphamide, doxorubicin and vincristine (LUCAV). Vancouver: BC Cancer Agency; 2002.

53. BC Cancer Agency Lymphoma Tumour Group. BCCA protocol summary for advanced indolent lymphoma using

cyclophosphamide, vincristine, prednisone (LYCVP). Vancouver: BC Cancer Agency; 2002.

54. BC Cancer Agency Sarcoma Tumour Group. BCCA protocol summary for adjuvant therapy for patients with newly diagnosed

Ewing's sarcoma/peripheral neuroectomdermal tumour (PNET) or rhabdomyosarcoma using vincristine, doxorubicin and

cyclophosphamide (SAVAC). Vancouver: BC Cancer Agency; 2002.

55. BC Cancer Agency Lymphoma Tumour Group. BCCA protocol summary for the treatment of Hodgkin's lymphoma using

cyclophosphamide, vincristine and prednisone (LYCCOP). Vancouver: BC Cancer Agency; 2002.

56. Leukemia/Bone Marrow Transplant Program of British Columbia. Intensive therapy and autography for Leukemia or Non-

Hodgkin's lymphoma (BMT IV BUCY). BC Cancer Agency, 2003.

57. Leukemia/Bone Marrow Transplant Program of British Columbia. Intensive multimodal therapy and autologous BMT for non-

Hodgkin's lymphoma (BMT LY 98-01). BC Cancer Agency, 2003.

58. BC Cancer Agency Lymphoma Tumour Group. BCCA protocol summary for the consolidation for lymphoma using etoposide,

cyclophosphamide and vincristine (LYECV). Vancouver: BC Cancer Agency; 2002.

59. Leukemia/Bone Marrow Transplant Program of British Columbia. High-dose chemotherapy with autologous HSCT for high-risk

nonseminomatous germ cell tumours (BMT 00-04). BC Cancer Agency, 2003.

60. Leukemia/Bone Marrow Transplant Program of British Columbia. Intensive multimodal therapy and hematopoietic progenitor

cell transplantation for progressive Hodgkin's disease (BMT 88-01). BC Cancer Agency, 2000.

61. Leukemia/Bone Marrow Transplant Program of British Columbia. Intensive multimodal therapy and autography for progressive

Hodgkin's disease (HD-CBV 00-01). BC Cancer Agency, 2004.

62. Leukemia/Bone Marrow Transplant Program of British Columbia. High dose etoposide and cyclophosphamide salvage therapy

for refractory acute leukemia (AL 91-02). BC Cancer Agency, 2004.

63. Leukemia/Bone Marrow Transplant Program of British Columbia. Treatment of Lymphoblastic lymphoma (NHL 98-01). BC

Cancer Agency, 2004.

64. BC Cancer Agency Lung Tumour Group. BCCA protocol summary for treatment of limited stage small cell lung cancer (SCLC)

alternating cyclophosphamide, doxorubicin and vincristine (CAV) with etoposide and cisplatin (EP) plus early thoracic irradiation

(LUALTL). Vancouver: BC Cancer Agency; 2002.

65. BC Cancer Agency Breast Tumour Group. BCCA Protocol summary for Palliative Therapy for metastatic Breast Cancer using

Doxorubicin and Cyclophosphamide (BRAVAC). Vancouver: BC Cancer Agency; 1999.

66. BC Cancer Agency Breast Tumour Group. BCCA Protocol summary for Inflammatory Breast Cancer using cyclophosphamide,

doxorubicin and fluorouracil. (BRINFCAF). Vancouver: BC Cancer Agency; 2004.

67. BC Cancer Agency Breast Tumour Group. BCCA Protocol summary for Inflammatory Breast Cancer using cyclophosphamide,

epirubicin and fluorouracil. (BRINFCEF). Vancouver: BC Cancer Agency; 2005.

68. BC Cancer Agency Breast Tumour Group. BCCA Protocol summary for Locally Advanced Breast Cancer using

cyclophosphamide, doxorubicin and fluorouracil. (BRLA2). Vancouver: BC Cancer Agency; 2004.

69. BC Cancer Agency Lymphoma Tumour Group. BCCA protocol summary for the treatment of Lymphoma with doxorubicin,

cyclophosphamide, vincristine and prednisone.(LYCHOP). Vancouver: BC Cancer Agency; 2005.

70. BC Cancer Agency Lymphoma Tumour Group. BCCA protocol summary for the treatment of Lymphoma with doxorubicin,

cyclophosphamide, vincristine prednisone and rituximab.(LYCHOP-R). Vancouver: BC Cancer Agency; 2005.

Cyclophosphamide

BC Cancer Agency Cancer Drug Manual© Page 14 of 14 Cyclophosphamide

Developed: September 1994

Revised: September 2005

71. BC Cancer Agency Sarcoma Tumour Group. BCCA protocol summary for BCCA Protocol Summary for Vincristine, Adriamycin

and Cyclophosphamide Combination for Patients with Newly Diagnosed Ewing's Sarcoma/Peripheral Neuroectodermal

Tumour(Pnet) and Rhabdomyosarcoma with Pelvic Primaries or Chemotherapy Induced Hematuria. SAVAC (r SAVAC + M is

Alternated with SAIME). Vancouver: BC Cancer Agency; 2003.

72. Aronoff GR, Berns JS, Brier ME, et al. Drug Prescribing in Renal Failure. 4th ed; 1999. p. 72-3.

73. Bischoff ME, Blau W, Wagner T, et al. Total body irradiation and cyclophosphamide in a conditioning regimen for unrelated

bone marrow transplantation in a patient with chronic myelogenous leukemia and renal failure on hemodialysis. Bone Marrow

Transplant 1998;22:591-3.

74. Perry JJ, Fleming RA, Rocco MV, et al. Administration and pharmacokinetics of high-dose cyclophosphamide with

hemodialysis in acute leukemia and end-stage renal disease. Bone Marrow Transplant 1999;23:839-42.

75. Haubitz M, Bohnenstengel F, Brunkhorst R, et al. Cyclophosphamide pharmacokinetics and dose requirements in patients with

renal insufficiency. Kidney Int 2002;61:1495-501.

76. Pizzo P, Poplack D. Principles and Practice of Pediatric Oncology. Fourth ed. Philadelphia: Lippincott Williams & Wilkins; 2002.

p. 246.

77. Pochedly C. Neoplastic Diseases of Childhood: harwood academic publishers; 1994. p. 218-20.