Cisplatin

DRUG NAME: Cisplatin

SYNONYM: CDDP,1 cis-Diamminedichloroplatinum,2 cis-dichlorodiammineplatinum(II),3 cis-Patinum II,2 DDP,4

COMMON TRADE NAME: PLATINOL®; PLATINOL-AQ®

CLASSIFICATION: Platinum compound5

Special pediatric considerations are noted when applicable, otherwise adult provisions apply.

MECHANISM OF ACTION:
6
Cisplatin is similar to the bifunctional alkylating agents. It covalently binds to DNA and disrupts DNA function. After
7,8
cisplatin enters the cells, the chloride ligands are replaced by water molecules. This reaction results in the
2
formation of positively charged platinum complexes that react with the nucleophilic sites on DNA. These platinum
complexes covalently bind to DNA bases using intra-strand and inter-strand cross-links creating cisplatin-DNA
6 9
adducts thus preventing DNA, RNA and protein synthesis. This action is cell cycle phase-nonspecific. Cisplatin
2
also has immunosuppressive, radiosensitizing, and antimicrobial properties.

PHARMACOKINETICS:
10
Interpatient variability systemic clearance resulting in variable blood platinum concentrations or AUCs
11
Oral Absorption not absorbed
12
Distribution rapidly diffuses into tissues ; highest concentrations found in the liver, prostate and
kidney; rapidly distributed into pleural effusions and ascitic fluid
9
cross blood brain barrier? not readily
13
volume of distribution ultrafilterable platinum*: 41 L/m²
5,10,12
plasma protein binding >90%
Metabolism undergoes non-enzymatic conversion to several inactive metabolites which are highly
11
bound to plasma proteins
active metabolite yes
9
inactive metabolite yes
7
Excretion primarily in the urine ; urinary excretion of ultrafilterable platinum* was substantially greater
14
after a 6-hour infusion than after a 15-minute injection
7 6
urine > 90% ; 25% excreted during the first 24 h
feces insignificant
terminal half life of ultrafilterable 20-45 min
7,10,15,16
platinum*
terminal half life of total 5 days or longer
7
platinum*
clearance 6.3 mL/min/kg
Gender no clinically important differences found
Elderly no clinically important differences found
11
Children terminal half life of ultrafilterable platinum* < 1 h
11
terminal half life of total platinum* 24-72 h
Ethnicity no clinically important differences found
Adapted from standard reference16 unless specified otherwise.

*Ultrafilterable platinum consists of non-protein-bound intact drug and metabolites, total platinum consists of all
7
platinum species, both protein-bound or –unbound. Note that it is the platinum that is usually measured.

©
BC Cancer Drug Manual Page 1 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

USES:
Primary uses: Other uses:
17
Adrenalcortical cancer Endometrial cancer
17
Anal cancer Lymphoma, CNS
17
* Bladder cancer Melanoma
17
Brain cancer Multiple myeloma
17
Breast cancer Pancreatic cancer
17
Cervical cancer Penile cancer
17
Esophageal cancer Prostate cancer
Gallbladder cancer
Gastric cancer
Germ cell tumour
Gestational trophoblastic neoplasia
Head and neck cancer
Liver cancer
Lung cancer, non-small cell
Lung cancer, small cell
Lymphoma, Hodgkin’s
Lymphoma, non-Hodgkin’s
Mesothelioma
Neuroendocrine tumours
Nasopharyngeal cancer
Osteosarcoma
* Ovarian cancer
Salivary gland cancer
* Testicular cancer
Thymoma
Urothelial cancer
*Health Canada approved indication

SPECIAL PRECAUTIONS:

Contraindications:
• history of hypersensitivity reaction to cisplatin or other platinum-containing compounds.
16

Caution:
• Administer with caution to individuals with pre-existing renal impairment, myelosuppression or hearing
13
impairment.
• Hydration is required to minimize nephrotoxicity. The manufacturer recommends pre-treatment hydration with 1
13
16
or 2 L of fluid infused 8-12 hours prior to a cisplatin dose. Hydration with NS, hypertonic saline infusion, and
7
mannitol, or furosemide-induced diuresis is used to effectively decrease cisplatin-induced nephrotoxicity. Lower
2
doses of cisplatin are given with less intensive hydration. For example, patients receiving doses of 35 mg/m have
2
been pre-treated with 500 mL NS over 1 hour, with no post-hydration. Patients receiving doses of 25 mg/m have
been pre-treated with vigorous oral hydration (e.g., 600-900 mL) the morning of treatment and 8 glasses (e.g.,
2000 mL/day) daily for a few days following treatment. For a suggested hydration guideline, see the
“Nephrotoxicity” paragraph following Side Effects table.
• Inadvertent substitution of cisplatin for carboplatin can result in a potentially fatal overdosage. Precautions
2

should be taken to avoid overdosing such as writing the cisplatin dose as a daily dose, not as a total cisplatin dose
used in one course of therapy. The manufacturer recommends that an alerting mechanism be instituted to verify
2
any order for cisplatin >100 mg/m per course every 3-4 weeks.

©
BC Cancer Drug Manual Page 2 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

16
Carcinogenicity: found to have a carcinogenic effect in laboratory animals.
16
Mutagenicity: shown to be a mild to moderate mutagen in the Ames test.
18
Fertility: Cisplatin therapy is associated with at least temporary infertility in the majority of patients. Among males
receiving cisplatin for testicular cancer, almost all became azospermic within the first two cycles of therapy, but
recovery of normal sperm morphology, motility, and sperm count occurred in 40% within 1.5-2 years.
9
Pregnancy: FDA Pregnancy Category D. There is positive evidence of human fetal risk, but the benefits from use
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).
9
Breastfeeding is not recommended as cisplatin is excreted in human milk.

SIDE EFFECTS:

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
19
clinically important.

ORGAN SITE SIDE EFFECT

Clinically important side effects are in bold, italics

allergy/immunology hypersensitivity (rare); see paragraph following Side Effects table

auditory/hearing ototoxicity (31%); see paragraph following Side Effects table
audiogram abnormalities (24%)
tinnitus (9%)
vestibular toxicity (rare)
blood/bone marrow/ myelosuppression (25-30%); WBC nadir 18-23 days (range 7.5-45), platelet nadir 18-
febrile neutropenia 23 days (range 7.5-45), recovery 39 days (range 13-62)
anemia (25-30)%; see paragraph following Side Effects table
12
cardiovascular arrhythmias
(arrhythmia)
bradycardia (rare)
cardiovascular (general) vascular toxicities may include myocardial infarction, cerebrovascular accident,
thrombotic microangiopathy, or cerebral arteritis
constitutional symptoms hiccoughs
20
dermatology/skin extravasation hazard: irritant
alopecia (uncommon)
rash (uncommon)
local soft tissue toxicity (rare)
12
endocrine glucose intolerance
21
gastrointestinal emetogenic potential: high
nausea and vomiting (> 90%); see paragraph following Side Effects table
delayed nausea and vomiting; see paragraph following Side Effects table
diarrhea

©
BC Cancer Drug Manual Page 3 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

ORGAN SITE SIDE EFFECT

Clinically important side effects are in bold, italics

loss of taste
12
pancreatitis
9
stomatitis
hepatic transient elevation of hepatic enzymes and bilirubin
metabolic/laboratory elevated serum amylase
2
electrolyte disturbances ; see paragraph following Side Effects table
hyperuricemia
musculoskeletal muscle cramps
neurology autonomic neuropathy
dorsal column myelopathy
Lhermitte’s sign
neurotoxicity, usually peripheral neuropathies; see paragraph following Side Effects
table
6
seizures (rare)
ocular/visual visual impairment (rare)
altered colour perception
blurred vision
cerebral blindness (infrequent)
optic neuritis
papilledema
renal/genitourinary nephrotoxicity (28-36%); see paragraph following Side Effects table
9
secondary malignancy acute leukemia (rare)
syndromes inappropriate antidiuretic hormone syndrome
22-26
vascular venous thromboembolic events

Adapted from standard references2,15,16 unless specified otherwise.

2
Anemia observed with cisplatin use may be caused by a decrease in erythropoietin or erythroid stem cells.
Cisplatin has been shown to sensitize red blood cells, sometimes resulting in a direct Coombs’ positive hemolytic
16
anemia.

Electrolyte disturbances can be serious and mainly includes hypomagnesemia, hypocalcemia and hypokalemia.
2
Hypophosphatemia and hyponatremia have occurred in some patients receiving cisplatin combination regimens.
These effects are due to renal tubular damage. Cisplatin greatly increases the urinary excretion of magnesium and
calcium; increased excretion of potassium, zinc, copper and amino acids also occurs. Hypomagnesemia and or
hypocalcemia may become symptomatic, with muscle irritability or cramps, clonus, tremor, carpopedal spasm and/or
tetany. Children may be at greater risk for developing hypomagnesemia.
10
Emetogenic effects are common with cisplatin therapy and may be serotonin-mediated. Acute nausea and
2
vomiting may occur within 1-6 (usually 2-3) hours after administration of cisplatin. This early period is the most
severe and usually lasts 8 hours, but can last up to 24 hours. Various levels of nausea, vomiting and anorexia may
persist for up to 5-10 days. Delayed nausea and vomiting can occur 24 hours or longer following chemotherapy
when complete emetic control had been attained on the day of cisplatin therapy. The incidence and severity of

©
BC Cancer Drug Manual Page 4 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

cisplatin-induced nausea and vomiting appear to be increased in: females, the young, high doses, rapid infusion and
combinations with other emetogenic drugs. Incidence and severity may be decreased in patients with a history of
chronic alcohol use. Acute nausea and vomiting can be prevented by pre-treatment with a 5-HT 3 antagonist (e.g.,
granisetron, ondansetron) plus a corticosteroid; this can be continued for the first 24 hours following chemotherapy.
Delayed nausea and vomiting should not routinely be treated with 5-HT 3 antagonists; although there is anecdotal
19
evidence that some patients can benefit from 5-HT 3 antagonists , generally these agents are ineffective more than
21
24 hours after chemotherapy. Corticosteroids are the cornerstone of the treatment for delayed nausea, although
12
other combinations are widely used. Refer to BC Cancer SCNAUSEA Protocol for details.

Nephrotoxicity is a major concern when prescribing cisplatin. Renal dysfunction due to cisplatin may manifest as
renal insufficiency, hypokalemia and hypomagnesemia. The risk for these adverse effects is related to the dose and
interval of cisplatin and may be minimized by adequate hydration. Geriatric patients may also be at increased risk.
 The manufacturer recommends pre-treatment hydration with 1 or 2 L of fluid infused 8-12 hours prior to a
16
cisplatin dose. Others suggest hydration with NS, hypertonic saline infusion, and mannitol, or furosemide-
7
induced diuresis to effectively decrease cisplatin-induced nephrotoxicity.

Refer to protocol by which patient is being treated. Numerous hydration regimens exist. Hydration regimens should
take into account the following conditions for the patient ; adequate renal function, clinically euvolemic prior to
administration of cisplatin, no contraindication to saline loading (e.g., uncompensated cardiac conditions, anasarca),
and ability to comply with recommended oral hydration protocol, or expectation that volume status can be
27
maintained (e.g., with fluids via enteral feeding tube or IV). Below is one suggested hydration regimen for adults.

2
Cisplatin (mg/m ) Hydration Electrolyte Additives* Comments
> 80 4000 mL* NS over 4 h KCl 20 mEq inpatient or medical daycare
MgSO 4 1 g unit admission to monitor urine
Mannitol 30 g output
60-80 2000 mL* NS over 2 h KCl 20 mEq
MgSO 4 1 g
Mannitol 30 g
40-60 1000 mL* NS over 1 h KCl 10 mEq includes regimens with cisplatin
MgSO 4 0.5 g administered over multiple days
<40 500 mL* NS over 30 min none includes regimens with cisplatin
administered over multiple days
*Volume may include hydration associated with the administration of other drugs (e.g., other chemotherapy agents, supportive IV
medications). The volumes and durations are minimum administration standards to accommodate the wide variation in clinical
practice in delivery of cisplatin. They should be individualized based on the clinical situation, which may affect the hydration
regimen and addition of electrolytes.

2
In children, for moderate to high-dose cisplatin give pre-hydration at 125mL/m /h for a minimum of 2 hours to
2 28
increase urine output to >100 mL/m /h (> 3 mL/kg/h). The hydration fluid most commonly used is D5NS + 20
29 2 28
mmol/L KCL. In post-hydration, maintain urine output at 65-100 mL/m /h with oral/IV fluids. Post-hydration is
29
usually D5NS + 20 mmol/L KCL + 10 mmol/L MgS04 +/- mannitol.

Nervous system effects are usually peripheral neuropathies and sensory in nature (e.g., parethesias of the upper
2
and lower extremities). They can also include motor difficulties (especially gait); reduced or absent deep-tendon
reflexes and leg weakness may also occur. Peripheral neuropathy is cumulative and usually reversible, although
12
recovery is often slow. Geriatric patients may be at greater risk for these cisplatin-induced neuropathies. Muscle
cramps have been reported, and usually occurred in patients with symptomatic peripheral neuropathy who received
relatively high cumulative doses of cisplatin. Lhermitte’s sign (a sensation during neck flexion resembling electric
shock) often is present with cisplatin-induced neuropathy. The occurrence of Lhermitte’s sign may coincide with the
onset of peripheral neuropathies, and can last for 2-8 months. When signs of neuropathy occur, cisplatin should be
discontinued.
2
Otic effects include tinnitus, with or without clinical hearing loss, and occasional deafness. Ototoxicity is cumulative
12
and irreversible and results from damage to the inner ear. These effects may be more severe in children than in
9
adults. The manufacturer recommends that audiograms be performed prior to initiating therapy and prior to each

©
BC Cancer Drug Manual Page 5 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

16
subsequent dose of drug. Initially, there is loss of high frequency acuity (4000 to 8000 Hz). When acuity is affected
in the range of speech, cisplatin should be discontinued under most circumstances and carboplatin substituted
where appropriate. Ototoxicity appears to be dose related. Higher cumulative doses, higher individual doses and
30
administration by IV bolus resulted in more severe ototoxicity, corresponding with higher plasma levels of
14
ultrafilterable platinum. Ototoxicity may be enhanced in patients with prior or simultaneous cranial irradiation.
Vestibular ototoxicity may increase with increasing cumulative dosage and may be more likely to occur in patients
with pre-existing vestibular dysfunction.

Sensitivity reactions can include anaphylactoid reactions consisting of facial edema, flushing, wheezing or
16
respiratory difficulties, tachycardia, and hypotension. These reactions can occur within a few minutes after IV
administration of cisplatin; diaphoresis, nasal stuffiness, rhinorrhea, conjunctivitis, generalized erythema,
apprehension, and sensation of chest constriction may also occur. Cisplatin-induced anaphylactoid reactions usually
2
have occurred after multiple cycles of cisplatin (e.g., at least 5 doses), but also can occur after the first dose. There
is a case report of a patient who experienced an anaphylaxis to cisplatin following nine previous uncomplicated
31 32
cycles. Some reactions may also be due to the mannitol that is given with cisplatin to prevent nephrotoxicity.
Occasionally, patients who experienced anaphylactoid reactions have been safely retreated with cisplatin following
pre-treatment with corticosteroids and/or antihistamines; however, such prophylaxis is not uniformly effective in
preventing recurrence.

INTERACTIONS:
AGENT EFFECT MECHANISM MANAGEMENT
etoposide synergistic antineoplastic possible impaired some protocols are
activity against testicular, elimination of etoposide in designed to take
small cell lung and, non- patients previously treated advantage of this effect;
small cell lung cancers with cisplatin monitor toxicity closely
nephrotoxic drugs such as increased risk of cumulative nephrotoxoixity use with extreme caution
aminoglycoside antibiotics nephrotoxicity during or shortly after
and amphotericin cisplatin
ototoxic drugs such as increased risk of ototoxicity cumulative ototoxicity carefully monitor for signs
aminoglycoside antibiotics of ototoxicity
or loop diuretics (e.g.,
ethacrynic acid,
furosemide)
phenytoin decreased phenytoin decreased absorption monitor serum levels of
serum levels and/or increased phenytoin
metabolism of phenytoin
33
pyridoxine decrease in cisplatin further investigation avoid concomitant use of
activity required pyridoxine with cisplatin
renally excreted drugs increase the serum levels reduced renal function monitor toxicity
of renally excreted drugs caused by cisplatin
Adapted from standard references2 unless specified otherwise.

SUPPLY AND STORAGE:

Injection: Cisplatin is available as sterile, unpreserved; single-dose vials (10 mg/10 mL, 50 mg/50 mL and 100
16
mg/100 mL) at a concentration of 1 mg/mL. Store at room temperature. Refrigeration or freezing will cause
precipitation. Protect from light.

For basic information on the current brand used at BC Cancer, see Chemotherapy Preparation and Stability
Chart in Appendix.

©
BC Cancer Drug Manual Page 6 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

SOLUTION PREPARATION AND COMPATIBILITY:

For basic information on the current brand used at BC Cancer, see Chemotherapy Preparation and Stability
Chart in Appendix.

Additional information:
• Do not use IV needles, syringes or sets that have aluminum components in the preparation or administration of
16
cisplatin. An interaction between aluminum and platinum will occur resulting in the formation of a black
precipitate, accompanied with a loss of potency.

Compatibility: consult detailed reference

PARENTERAL ADMINISTRATION:
BC Cancer administration guideline noted in bold, italics
Subcutaneous no information found
Intramuscular no information found
Direct intravenous not to be administered by the direct IV route
Intermittent infusion over 15-30 minutes
Continuous infusion over 6-24 hours (administration over 24 hours may
decrease nausea, vomiting and nephrotoxicity)
Intraperitoneal hyperthermic intraperitoneal chemotherapy (HIPEC):
pump solution into abdominal cavity and circulate as per
protocol using hyperthermia pump; solutions and dwell
34-38
time vary by protocol
5
Intrapleural has been used
Intrathecal no information found
15
Intra-arterial has been used
39
Intravesical has been used

DOSAGE GUIDELINES:

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 suppression due to
cytotoxic/radiation therapy or with other toxicities.

Adults:
BC Cancer usual dose noted in bold, italics
Cycle Length:
Intravenous:
40,41 2
1 week : 25-40 mg/m IV on day 1
2
(total dose per cycle 25-40 mg/m )

42 2
2 weeks : 30 mg/m IV for one dose on days 1-3
2
(total dose per cycle 90 mg/m )

43-48 2
3 weeks : 20-100 mg/m IV on day 1
2
(total dose per cycle 20-100 mg/m )

©
BC Cancer Drug Manual Page 7 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

BC Cancer usual dose noted in bold, italics

Cycle Length:
49 2
3 weeks : 60 mg/m IV once daily for 2 consecutive days starting on
day 1
2
(total dose per cycle 120 mg/m )

50 2
3 weeks : 20 mg/m IV for one dose on days 1 and 5
2
(total dose per cycle 40 mg/m )

47 2
3 weeks : 30 mg/m IV for one dose on days 1 and 8
2
(total dose per cycle 60 mg/m )

51-56 2
3 weeks : 25 mg/m IV for one dose on days 1-3
2
(total dose per cycle 75 mg/m )

57-60 2
3 weeks : 20 mg/m IV for one dose on days 1-5
2
(total dose per cycle 100 mg/m )

61,62 2
4 weeks : 70-100 mg/m IV on day 1
2
(total dose per cycle 70-100 mg/m )

63,64 2
4 weeks : 25-30 mg/m IV once daily for 3 consecutive days starting on
day 1
2
(total dose per cycle 75-90 mg/m )

65 2
6 weeks : 75 mg/m IV for one dose on day 1
2
(total dose per cycle 75 mg/m )

66 2
Concurrent radiation: 1 week : 40 mg/m IV for one dose on day 1
2
(total dose per cycle 40 mg/m )

60 2
2 weeks 100 mg/m IV for one dose on day 1
2
(total dose per cycle 100 mg/m )

67 2
3 weeks : 100 mg/m IV for one dose on day 1
2
(total dose per cycle 100 mg/m )

68 2
4 weeks : 25 mg/m IV for 3 consecutive days starting on day 1
2
(total dose per cycle 75 mg/m )

Dosage in myelosuppression: modify according to protocol by which patient is being treated; if no guidelines
available, refer to Appendix 6 "Dosage Modification for Myelosuppression"

Dosage in renal failure: Suggested dose modifications:

Creatinine clearance (mL/min) Dose
≥60 100%
45-59 75% cisplatin or go to carboplatin
option (if available)

©
BC Cancer Drug Manual Page 8 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

BC Cancer usual dose noted in bold, italics

Cycle Length:
<45 hold cisplatin or delay with additional
IV fluids or go to carboplatin option
(if available)

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

Serum Creatinine in µmol/L
* For males N=1.23; for females N=1.04

Dosage in hepatic failure: no adjustment required

9
Dosage in dialysis: removable by dialysis, but only within 3 h of administration

2
Children :
Cycle Length:
2
Intravenous: 1 week: 30 mg/m IV one dose on day 1

2
3 weeks: 90 mg/m IV one dose on day 1

2
3-4 weeks: 60 mg/m IV one dose on day 1 and day 2

REFERENCES:

1. Matsusaka S, Nagareda T, Yamasaki H. Does cisplatin (CDDP)function as a modulator of 5-fluorouracil (5-FU) antitumor action?
A study based on a clinical trial. Cancer Chemotherapy Pharmacology 2005;55:387-392.
2. McEvoy GK, editor. AHFS 2004 Drug Information. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.;
2004. p. 929-945.
3. Meyer KB, Madias NE. Cisplatin nephrotoxicity. Mineral & Electrolyte Metabolism. 1994;20(4):201-13.
4. Farris FF, Dedrick RL, King FG. Cisplatin pharmacokinetics: applications of a physiological model. Toxicology Letters 1988;43(1-
3):117-37.
5. Pizzo P, Poplack D. Principles and Practice of Pediatric Oncology. Fourth ed. Philadelphia: Lippincott Williams & Wilkins; 2002.
p. 256-259.
6. Chabner BA, Longo DL. Cancer chemotherapy and biotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001. p.
453-459.
7. Go R, Adjel A. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol
1999;17(1):409-422.
8. Nieto Y. DNA-binding agents. Cancer Chemotherapy & Biological Response Modifiers 2003;Annual 21:Chapter 8.
9. Cisplatin. USP DI. Volume 1. Drug information for the health care professional. 20th ed. Englewood, Colorado: Micromedex, Inc.;
2002.
10. Murry DJ. Comparative clinical pharmacology of cisplatin and carboplatin. Pharmacotherapy 1997;17(5 Pt 2):140S-145S.
11. Crom WR, Glynn-Barnhart AM, Rodman JH, et al. Pharmacokinetics of Anticancer Drugs in Children. Clinical Pharmacokinetics
1987;12:179-182.
12. O'Dwyer P, Stevenson J, Johnson S. Clinical Pharmacokinetics and Administration of Established Platinum Drugs. Drugs 2000
2000;59 Suppl. 4:19-27.
13. Repchinsky C. Compendium of Pharmaceuticals and Specialties. Ottawa, Ontario: Canadian Pharmacists Association; 2004. p.
431-432.
14. Belt RJ, Himmelstein KJ, Patton TF, et al. Pharmacokinetics of Non-Protein-Bound Platinum Species Following Adminisration
of cis-Dichlorodiammineplatinum(II). Cancer Treatment Reports 1979;63(No. 9-10):1515-1521.
15. McEvoy GK, editor. AHFS 1989 Drug Information. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.;
1989. p. 929-945.
16. Mayne Pharma (Canada) Inc. Cisplatin product monograph. Montreal, Quebec; 2003.
17. Lexi-Drugs® (database on the Internet). Cisplatin. Lexi-Comp Inc., 16 March 2016. Available at: http://online.lexi.com.
Accessed 31 March 2016.
18. Perry M, M.D. FACP. The Chemotherapy Source Book. Baltimore, Maryland: Williams & Wilkins; 1992. p. 405-409.
19. Christopher Lee MD. Personal Communication. Medical Oncologist, BC Cancer Agency, Fraser Valley Cancer Centre; 2005.

©
BC Cancer Drug Manual Page 9 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

20. BC Cancer Agency Provincial Systemic Therapy Program. Policy III-20: Prevention and Management of Extravasation of
Chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 1 February 2004.
21. BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in
Adults. Vancouver, British Columbia: BC Cancer Agency; May 1999.
22. Health Canada. Summary Safety Review - Cisplatin: Assessing the Potential Risk of Blood Clots in the Veins (venous
thromboembolism). 12 February 2016. Available at: http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/index-eng.php.
Accessed 8 April 2016.
23. Health Canada. Health Product InfoWatch - Review Article: Cisplatin and venous thrombembolism. Health Canada Marketed
Health Products Directorate, January 2015. Available at: http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/index-eng.php.
24. Hospira Healthcare Corporation. Cisplatin injection® product monograph. Saint-Laurent, Quebec; 23 July 2015.
25. Seng S, Liu Z, Chiu SK, et al. Risk of venous thromboembolism in patients with cancer treated with cisplatin: a systematic
review and meta-analysis. J Clin Oncol 2012;30(35):4416-4426.
26. Moore RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based
chemotherapy: a large retrospective analysis. J Clin Oncol 2011;29(25):3466-3473.
27. BC Cancer Agency Genitourinary Tumour Systemic Policy Group. Administration of cisplatin in the outpatient setting. BC
Cancer Agency; 8 June 2000.
28. Ablin AR. Supportive Care of Children with Cancer. 2nd ed. Baltimore, Maryland: John Hopkins University Press; 1997.
29. Roberta Esau. Personal communication. Pharmacist, BC Children’s Hospital; 10 May 2016.
30. Balis FM, Holcenberg JS, Bleyer WA. Clinical Pharmacokinetics of Commonly Used Anticancer Drugs. Clinical
Pharmacokinetics 1983;8:202-232.
31. Basu R, Rajkumar A, Datta RN. Anaphylaxis to cisplatin following nine previous uncomplicated cycles. Int J Clin Oncol
2002;7:365-367.
32. Ackland SP, Hillcoat BL. Immediate hypersensitivity to mannitol: a potential cause of apparent hypersensitivity to cisplatin
[letter]. Cancer Treatment Reports 1985;69(5):562-3.
33. Wiernik P, Yeap B, Vogl S, et al. Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for
treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. Cancer Investigation 1992;10(1):1-
9.
34. Yan TD, Deraco M, Baratti D, et al. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant
Peritoneal Mesothelioma: Multi-Institutional Experience. Journal of Clinical Oncology 2009;27(36):6237-6242.
35. Elias D, Gilly F, Boutitie F, et al. Peritoneal Colorectal Carcinomatosis Treated With Surgery and Perioperative Intraperitoneal
Chemotherapy: Retrospective Analysis of 523 Patients From a Multicentric French Study. Journal of Clinical Oncology
2010;28(1):63-68.
36. HayesJordan A, Anderson PM. The diagnosis and management of desmoplastic small round cell tumor: a review.
Curr.Opin.Oncol. 2011;23(4):385-389.
37. BC Cancer Agency Sarcoma Tumour Group. (SAHIPEC) BCCA Protocol Summary for Hyperthermic Intraperitoneal
Chemotherapy (HIPEC) for Patients with Peritoneal Desmoplastic Small Round Cell Tumour (DSRCT) Using CISplatin. Vancouver,
British Columbia: BC Cancer Agency; I January 2016.
38. BC Cancer Agency Gastrointestinal Tumour Group. (GIPMHIPEC) BCCA Protocol Summary for Hyperthermic Intraperitoneal
Chemotherapy (HIPEC) for Patients with Peritoneal Mesothelioma Using DOXOrubicin, CISplatin, and PACLitaxel. Vancouver,
British Columbia: BC Cancer Agency; I December 2015.
39. Dorr RT, Von-Hoff DD. Drug monographs. Cancer chemotherapy handbook. 2nd ed. Norwalk, Conneticut: Appleton and Lange;
1994. p. 286-293.
40. BC Cancer Agency Gastrointestinal Tumour Group. (GIFUC) BCCA Protocol summary for palliative chemotherapy for upper
gastrointestinal tract cancer (gastric, esophageal, gall bladder carcinoma and cholangiocarcinoma) using infusional fluorouracil and
cisplatin. Vancouver: BC Cancer Agency; 2001.
41. BC Cancer Agency Head and Neck Tumour Group. BCCA Protocol summary for recurrent and metastatic nasopharyngeal
cancer using cisplatin and etoposide (HNDE). Vancouver: BC Cancer Agency; 2004.
42. BC Cancer Agency Gynecology Tumour Group. BCCA Protocol summary for treatment for high risk gestational trophoblastic
cancer (GOTDHR). Vancouver: BC Cancer Agency; 2005.
43. BC Cancer Agency Genitourinary Tumour Group. BCCA Protocol summary for palliative therapy for urothelial carcinoma using
cisplatin and gemcitabine (GUAVPG). Vancouver: BC Cancer Agency; 2002.
44. BC Cancer Agency Genitourinary Tumour Group. BCCA protocol summary for neo-adjuvant therapy for urothelial carcinoma
using cisplatin and gemcitabine (UGUNAJPG). Vancouver: BC Cancer Agency; 2005.
45. BC Cancer Agency Genitourinary Tumour Group. (GUVIP2) BCCA Protocol Summary for Nonseminoma
Consolidation/Salvage Protocol Using Etoposide, Cisplatin, Ifosfamide, Mesna. Vancouver, British Columbia: BC Cancer Agency; 1
February 2007.
46. BC Cancer Agency Lung Tumour Group. BCCA protocol summary for adjuvant cisplatin and etoposide following resection of
stage I, II and IIIA non-small cell lung cancer (LUAJEP). Vancouver: BC Cancer Agency; 2001.
47. BC Cancer Agency Lung Tumour Group. BCCA protocol summary for treatment of advanced non-small cell lung cancer with
platinum and gemcitabine (LUAVPG). Vancouver: BC Cancer Agency; 2005.
48. BC Cancer Agency Lung Tumour Group. BCCA protocol summary for first-time treatment of advanced non-small cell lung
cancer with cisplatin and docetaxel (LUCISDOC). Vancouver: BC Cancer Agency; 2005.
49. BC Cancer Agency Gynecology Tumour Group. BCCa protocol summary for treatment of small cell carcinoma of cervix using
paclitaxel, cisplatin, etoposide and carboplatin with radiation (GOSMCC2). Vancouver: BC Cancer Agency; 2002.
50. BC Cancer Agency Genitourinary Tumour Group. BCCA protocol summary for consolidation/salvage treatment for germ cell
carcinoma using vinblastine, cisplatin, ifosfamide and mesna (GUVEIP). Vancouver: BC Cancer Agency; 2003.

©
BC Cancer Drug Manual Page 10 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019
 Cisplatin

51. BC Cancer Agency Genitourinary Tumour Group. BCCA protocol summary for therapy of genitourinary small cell tumours with
a platin and etoposide (GUSCPE). Vancouver: BC Cancer Agency; 2003.
52. BC Cancer Agency Head and Neck Tumour Group. BCCA Protocol summary for advanced head and neck cancer using
cisplatin and fluorouracil (HNFUP). Vancouver: BC Cancer Agency; 2005.
53. BC Cancer Agency Head and Neck Tumour Group. Cisplatin and etoposide for recurrent and metastatic nasopharyngeal
cancer. (HNDE). Vancouver: BC Cancer Agency; 1999.
54. BC Cancer Agency Lung Tumour Group. BCCA protocol summary for treatment of limited stage small cell lung cancer
alternating cyclophosphamide, doxorubicin and vincristine with etoposide and cisplatin plus early thoracic irradiation (LUALTL).
Vancouver: BC Cancer Agency; 2002.
55. BC Cancer Agency Lung Tumour Group. BCCA protocol summary for palliative therapy of selected solid tumours using
cicplatin and etoposide (LUPE). Vancouver: BC Cancer Agency; 2004.
56. BC Cancer Agency Lung Tumour Group. BCCA protocol summary for treatment of limited stage small-cell lung cancer with
etoposide and cisplatin and early thoracic irradiation (LUPESL). Vancouver: BC Cancer Agency; 2004.
57. BC Cancer Agency Gynecology Tumour Group. BCCA Protocol summary for non-dysgerminomatous ovarian germ cell cancer
using bleomycin, etoposide and cisplatin. Vancouver: BC Cancer Agency; 2001.
58. BC Cancer Agency Gynecology Tumour Group. BCCA Protocol summary for therapy of dysgerminomatous ovarian germ cell
cancer using cisplatin and etoposide. Vancouver: BC Cancer Agency; 2001.
59. BC Cancer Agency Genitourinary Tumour Group. BCCA Protocol Summary for Bleomycin, Etoposide, Cisplatin for
Nonseminoma Germ Cell Cancers (GUBEP). Vancouver: BC Cancer Agency; 2002.
60. BC Cancer Agency Genitourinary Tumour Group. BCCA protocol summary for therapy for etoposide - cisplatin protocol for
germ cell cancers (GUBP). Vancouver: BC Cancer Agency; 2005.
61. BC Cancer Agency Genitourinary Tumour Group. BCCA protocol summary for therapy for transitional cell cancers of the
urothelium using methotrexate, vinblastine, doxorubicin and cisplatin (GUMVAC). Vancouver: BC Cancer Agency; 2003.
62. BC Cancer Agency Lung Tumour Group. BCCA protocol summary for combined chemotherapy and radiation treatment for
stage 3 non-small cell lung cancer (LUCMT-1). Vancouver: BC Cancer Agency; 2005.
63. BC Cancer Agency Gynecology Tumour Group. BCCA Protocol Summary for Treatment of Advanced/Recurrent Non-Small
Cell Cancer of the Cervix with Cisplatin and Etoposide (GOCXADV). Vancouver: BC Cancer Agency; 2000.
64. BC Cancer Agency Genitourinary Tumour Group. BCCA protocol summary for combined modality therapy for sqamous cell
cancer of the genitourinary system using fluorouracil and cisplatin (GUFUP). Vancouver: BC Cancer Agency; 2005.
65. BC Cancer Agency Neuro-Oncology Tumour group. BCCA Protocol Summary for adjuvant lomustine, cisplatin and vincristine
in adult high-risk medulloblastoma or other primitive neuro-ectodermal tumour (PNET) - CNCCV. Vancouver: BC Cancer Agency;
2002.
66. BC Cancer Agency Gynecology Tumour Group. BCCA Protocol summary for treatment of high risk squamous cell carcinoma of
cervix with concurrent cisplatin and radiation. (GOCXRADC). Vancouver: BC Cancer Agency; 2002.
67. BC Cancer Agency Head and Neck Tumour Group. BCCA Protocol summary for combined chemotherapy and radiation
treatment for locally advanced squamous cell carcinoma of the head and neck (HNCMT2). Vancouver: BC Cancer Agency; 2004.
68. BC Cancer Agency Gastrointestinal Tumour Group. (GIEFUP) BCCA Protocol Summary for combined modality therapy for
locally advanced esophageal cancer using cisplatin, infusional fluorouracil and radiation therapy. (GIEFUP). Vancouver: BC Cancer
Agency; 2000.

©
BC Cancer Drug Manual Page 11 of 11 Cisplatin
Developed: September 1994
Limited Revision: 1 July 2019