Oxaliplatin

DRUG NAME: Oxaliplatin

SYNONYM(S): ACT-078, l-OHP, LOHP, oxalatoplatin, oxaliplatinum

COMMON TRADE NAME(S): ELOXATIN

CLASSIFICATION: Alkylating agent

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

MECHANISM OF ACTION:

Oxaliplatin belongs to a new class of platinum agent. It contains a platinum atom complexed with oxalate
and diaminocyclohexane (DACH). The bulky DACH is thought to contribute greater cytotoxicity than cisplatin
1
and carboplatin. The exact mechanism of action of oxaliplatin is not known. Oxaliplatin forms reactive
platinum complexes which are believed to inhibit DNA synthesis by forming interstrand and intrastrand
cross-linking of DNA molecules. Oxaliplatin is not generally cross-resistant to cisplatin or carboplatin,
1,2
possibly due to the DACH group and resistance to DNA mismatch repair. Preclinical studies have shown
3
oxaliplatin to be synergistic with fluorouracil and SN-38, the active metabolite of irinotecan. Oxaliplatin is a
4,5 6
radiation-sensitizing agent. It is cell cycle phase-nonspecific.

PHARMACOKINETICS:
6
Interpatient variability inter- and intra-subject variability is low
Distribution minimal in plasma; accumulation in erythrocytes does not diffuse into plasma or act as
a drug reservoir
cross blood brain barrier? no information found
6
volume of distribution ultrafilterable platinum*: 582 261 L
plasma protein binding 70-95%
7
Metabolism rapid nonenzymatic biotransformation to reactive platinum complexes
6
active metabolite(s) DACH platinum species
6
inactive metabolite(s) several conjugates, including the 1,2-DACH-platinum
3
dichloride (2%) associated with neurotoxicity
8
Excretion platinum is mainly by renal excretion and tissue distribution, while platinum metabolites
1
are mainly by renal excretion
9
urine 50% within 3 days
9
feces minimal
6
terminal half life ultrafilterable platinum*: 273 19 h
1
platinum elimination from erythrocytes: 48 days
6
clearance ultrafilterable platinum*: 10.1 3.07 L/h
Adapted from reference1 unless specified otherwise.
Ultrafilterable platinum consists of oxaliplatin and free oxaliplatin metabolites.

BC Cancer Agency Cancer Drug Manual Page 1 of 9 Oxaliplatin
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Revised: 1 December 2016
 Oxaliplatin

USES:
Primary uses: Other uses:
10-12 13
*Colorectal cancer Breast cancer
14
Gastric cancer
15
Germ cell cancer
16
Head and neck cancer
17
Lung cancer, non-small cell
18
Lymphoma, non-Hodgkins
19,20
Mesothelioma
21,22
Ovarian cancer
23
Pancreatic cancer
24
Prostate cancer
*Health Canada Therapeutic Products Programme approved indication

No pediatric indications.

SPECIAL PRECAUTIONS:

Contraindications:
history of hypersensitivity reaction to oxaliplatin or other platinum agents (eg, cisplatin, carboplatin)
6

peripheral sensory neuropathy interfering with function or severe renal dysfunction (CrCl < 30 mL/min)
6

Caution:
QT prolongation and torsades de pointes are reported; use caution in patients with history of QT
prolongation or cardiac disease and those receiving concurrent therapy with other QT prolonging
25,26
medications. Correct electrolyte disturbances prior to treatment and monitor periodically.

Special populations:
Elderly patients over 65 may be at higher risk of severe (grades 3-4) diarrhea.
11

Women may be at higher risk of severe (grades 3-4) neutropenia.

11

Carcinogenicity: Oxaliplatin is considered a probable carcinogen, although carcinogenic studies have not
6
been done.
6
Mutagenicity: Mutagenic in mammalian in vitro mutation chromosome tests.

Fertility: no information found

6
Pregnancy: Oxaliplatin produced embryo-fetal toxicity in rats.
6
Breastfeeding is not recommended due to the potential secretion into breast 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 clinically important. Incidence of adverse events is generally similar when
oxaliplatin is used as a single agent or in combination with fluorouracil and leucovorin, although severe
(grades 3-4) diarrhea, nausea and vomiting, and neurotoxicity are more common with combination
1,27
therapy.

BC Cancer Agency Cancer Drug Manual Page 2 of 9 Oxaliplatin
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 Oxaliplatin

ORGAN SITE SIDE EFFECT

Clinically important side effects are in bold, italics
6,28,29
allergy/immunology anaphylaxis (0.5-2%)
blood/bone marrow anemia (64-83%, severe 4-5%)
febrile neutropenia febrile neutropenia (< 2%)
30
immune hemolytic anemia (rare)
neutropenia: single agent (15%, severe 3%); with fluorouracil and leucovorin (66%,
severe 38%)
thrombocytopenia: single agent (41%, severe 3%); with fluorouracil and leucovorin (76%,
severe 4%)
constitutional symptoms fever (36%)
31-36 37
dermatology/skin extravasation hazard: irritant ; treat as vesicant ; see paragraph following Side
Effects table
alopecia (2%)
38
gastrointestinal emetogenic potential: high moderate
diarrhea: single agent (41%, severe 5%); with fluorouracil and leucovorin (58%, severe
10%)
mucositis: single agent (4%, severe 2%); with fluorouracil and leucovorin (42%, severe
8%)
nausea, vomiting (69-71%, severe 12-14%)
hepatic liver function abnormalities (46%, severe 12%)
infection infection (23%)
25,26,39,40
investigations QT prolongation, torsades de pointes
41-45
neurology central neurotoxicity/reversible posterior leukoencephalopathy syndrome (<1%) ; see
paragraph following Side Effects table
neuropathy, sensory (85-95%); see paragraph following Side Effects table
pharyngolaryngeal dysesthesia (1-2%); see paragraph following Side Effects table
renal/genitourinary renal dysfunction (3%, severe < 1%)
46 46-48
vascular thromboembolic events, including deep vein thrombosis (1-10%)
Adapted from reference6 unless otherwise specified.

Peripheral sensory neuropathy is cumulative, dose-related and usually reversible a few months after
stopping treatment. Symptoms include sensory ataxia and dysesthesia of the limbs, mouth, throat and
1,38
larynx, and may be exacerbated by exposure to cold (eg, touching cold surface, drinking cold liquid). The
incidence of grade 2 neuropathy is 10% after 3 treatment cycles and 50% after 10 cycles. Grade 3
neuropathy occurs in 10% after 9 cycles and 50% after 14 cycles, is reversible in 74% of the cases, and
begins to recover after 13 weeks. Paresthesia interfering with function (eg, buttoning clothing, holding
objects, writing) is seen in 16% of patients after 4 months of treatment and rarely leads to oxaliplatin
11
withdrawal. Unlike cisplatin, oxaliplatin neuropathy is related to injury to small rather than large sensory
17
fibres. The use of calcium gluconate or magnesium sulfate infusions pre- and/or post oxaliplatin treatment
49-52
do not appear to reduce or protect against oxaliplatin-induced neurotoxicity.

Gabapentin PO 100 mg twice daily, with increments of 100 mg PO daily as needed, may be effective in
53 54
some patients to reduce oxaliplatin neuropathy, while carbamazepine does not appear to be effective.
Other agents used with some success include alpha-lipoic acid IV 600 mg weekly for 3-5 weeks, then
55
followed by oral 600 mg three times daily. Oxaliplatin delivered according to 24-hour biologic rhythms
1,12
(chronomodulated) appears to be associated with less peripheral neuropathy than fixed rate infusion.

Pharyngolaryngeal dysesthesia with sporadic reduced sensitivity of the larynx and pharynx is seen in 1-
2% of patients shortly after drug infusion. Symptoms usually resolve within hours of onset but the feeling of
difficulty in breathing or swallowing may be distressing to the patient. Treatment is usually not needed,

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 Oxaliplatin

although antihistamines and bronchodilators have been used. To prevent recurrence, infusion time should
1,6
be extended to 6 hours with subsequent treatments.

Reversible posterior leukoencephalopathy syndrome (RPLS; also known as PRES) has been
41-45 42,43
associated with oxaliplatin, which may cause endothelial dysfunction and lead to vasogenic edema.
Clinical presentation includes altered mental status, seizures, headache, and loss of vision with associated
42
radiographic abnormality on MRI or CT. Symptom onset may be delayed relative to treatment, with cases
43,44,56
reported 8 to 12 days after the first infusion and as long as 6 weeks post treatment. Management is
usually supportive, with control of hypertension, electrolyte replacement, seizure management, and
42,43
discontinuation of oxaliplatin. Although usually reversible, permanent disability and fatalities have been
42,43
reported.

Management of extravasation: Extravasation of oxaliplatin may sometimes cause severe local

31-36
inflammation and potentially tissue necrosis. The optimal non-pharmacological management of
oxaliplatin extravasation is unclear. However, it has been suggested that warm compresses may be
33,57,58
preferred over cool compresses which may theoretically precipitate or worsen peripheral sensory
neuropathy. For management of extravasation reactions, see BCCA Policy Number III-20 Prevention and
Management of Extravasation of Chemotherapy.

INTERACTIONS:

AGENT EFFECT MECHANISM MANAGEMENT

59
fluorouracil no influence on fluorouracil
pharmacokinetics
60-62
irinotecan induction of irinotecan- may potentiate irinotecan give prophylactic atropine
related cholinergic syndrome inhibition of acetylcholinesterase before irinotecan
63
topotecan no effects on topotecan
pharmacokinetics
64
warfarin significantly higher incidence unknown; possible synergy of for oxaliplatin/fluorouracil
of INR elevation when anticoagulant effect of based regimens only:
administered with fluorouracil by oxaliplatin monitor INR regularly
oxaliplatin/fluorouracil based during and for one month
regimens following completion of
treatment; adjust warfarin
dose as needed

Avoid concurrent use of QT/QTc-prolonging drugs if possible. Use caution with drugs that may disrupt electrolyte levels.
Correct electrolytes as needed and monitor as applicable.25

SUPPLY AND STORAGE:

Injection:
sanofi-aventis Canada Inc. supplies oxaliplatin as 50 mg and 100 mg single-use vials of sterile lyophilized
powder and 50 mg, 100 mg, and 200 mg single-use vials of sterile preservative-free aqueous solution in a
concentration of 5 mg/mL. Store at room temperature. Do not freeze. Protect from light for long-term
45
storage.

Sandoz Canada Inc. supplies oxaliplatin as 50 mg, 100 mg, 150 mg, and 200 mg single-use vials of
preservative-free aqueous solution in a concentration of 5 mg/mL. Store at room temperature. Do not freeze.
65
Protect from light.

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

BC Cancer Agency Cancer Drug Manual Page 4 of 9 Oxaliplatin
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Revised: 1 December 2016
 Oxaliplatin

SOLUTION PREPARATION AND COMPATIBILITY:

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

Additional information:
Aluminum-containing IV needles, syringes or sets should not be used to prepare or administer oxaliplatin;
6
aluminum reacts with platinum from oxaliplatin to form a precipitate, resulting in loss of potency.
Oxaliplatin can be co-administered with leucovorin infusion using a Y-line placed immediately before the
66,67
site of injection; however, the drugs should not be combined in the same infusion bag.

Compatibility: consult detailed reference

PARENTERAL ADMINISTRATION:
BCCA administration guideline noted in bold, italics
Subcutaneous no information found
Intramuscular no information found
Direct intravenous no information found
Intermittent infusion in 500 mL D5W over 2 h ;
11

in 250-500 mL D5W over 30 min , 3 h , or 6 h ;

9 68 12

administer before fluoropyrimidines (eg, fluorouracil) ;

6

do not piggyback or flush lines with sodium chloride solution

6

12
Continuous infusion chronomodulated infusion over 5 days using programmable-in-time pump
Intraperitoneal hyperthermic intraperitoneal chemotherapy (HIPEC): pump solution into abdominal
cavity and circulate as per protocol using hyperthermia pump; solutions and dwell time
69-71
vary by protocol
Intrapleural no information found
Intrathecal no information found
72
Intra-arterial investigational, over 4 h
Intravesical no information found

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 (ANC). Dosage may be reduced, delayed or discontinued in patients with bone marrow
depression due to cytotoxic/radiation therapy or in patients with other toxicities.

Adults:
BCCA usual dose noted in bold, italics
Cycle Length:
68
Intravenous: 1 week : 35 mg/m IV for one dose on day 1
1,10,73
2 weeks : 85 mg/m (range 80-100 mg/m) IV for one dose on
day 1
1,3,73
3 weeks : 130 mg/m (range 85-135 mg/m) IV for one dose on
day 1

30 mg/m/day by continuous IV infusion for 5

consecutive days
74
(total dose per cycle 150 mg/m)

35 mg/m/day by chronomodulated IV infusion for 5

consecutive days
74
(total dose per cycle 175 mg/m)

BC Cancer Agency Cancer Drug Manual Page 5 of 9 Oxaliplatin
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Revised: 1 December 2016
 Oxaliplatin

4 weeks: 85 mg/m IV for one dose on days 1 and 15

75
(total dose per cycle 170 mg/m)

50 days: 50 mg/m IV for one dose on days 1,8, 15, 22, 29, 36
76
(total dose per cycle 300 mg/m)
4
Concurrent radiation: investigational, 130 mg/m IV on days 1 and 29 concurrent with radiation

Dosage in myelosuppression: modify according to protocol by which patient is being treated; if no

guidelines available, refer to Appendix "Dosage Modification for
Myelosuppression"
6
Dosage in neurotoxicity:

Duration of Neurotoxicity Severity Dose

6,11 troublesome
> 7 days reduce dose from: 130 mg/m to 100 mg/m; or from 85
mg/m to 65 mg/m; or from 65 mg/m to 50 mg/m
6
persists until next cycle no functional reduce dose from 85 mg/m to 65 mg/m
impairment
11
> 7 days functional reduce dose from 85 mg/m to 50 mg/m
impairment
6,11
persists until next cycle functional discontinue*
impairment
*if neurotoxicity improves following discontinuation, resumption of therapy may be considered6,77

Dosage in renal failure:

CrCl (mL/min) Dose
78
> 30 100%
< 30 no information found

CrCl (mL/min) = N x (140 - Age) x wt (kg)

Serum Creatinine (mol/L)

where N = 1.04 for females and 1.23 for males

6
Dosage in hepatic failure: no adjustment required for mild to moderate liver dysfunction ; no
information found regarding severe hepatic insufficiency

Dosage in dialysis: no information found

45
Children: has been used; effectiveness has not been established

REFERENCES:

1. Wiseman LR, Adkins JC, Plosker GL, et al. Oxaliplatin: a review of its use in the management of metastatic colorectal
cancer. Drugs & Aging 1999;14(6):459-75.
2. Misset JL, Bleiberg H, Sutherland W, et al. Oxaliplatin clinical activity: a review. Critical Reviews in Oncology-
Hematology 2000;35(2):75-93.
3. Cvitkovic E, Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer. Seminars in Oncology
1999;26(6):647-62.
4. Freyer G, Bossard N, Romestaing P, et al. Oxaliplatin (OXA), 5-fluorouracil (5FU), L-folinic acid (FA) and concomitant
irradiation in patients with rectal cancer: A phase 1 study. Proceedings of the American Society of Clinical Oncology
2000;19:260a-abstract 1012.
5. Carraro S, Roca E, Cartelli C, et al. Oxaliplatin (OXA), 5-fluorouracil (5-Fu) and leucovorin (LV) plus radiotherapy in
unresectable rectal cancer (URC): Preliminary results. Proceedings of the American Society of Clinical Oncology
2000;19:291a-abstract 1140.

BC Cancer Agency Cancer Drug Manual Page 6 of 9 Oxaliplatin
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Revised: 1 December 2016
 Oxaliplatin

6. Sanofi-Synthelabo France. Eloxatin: Summary of product characteristics (Europe). 1 October 1999.

7. Culy CR, Clemett D, Wiseman LR. Oxaliplatin. A review of its pharmacological properties and clinical efficacy in
metastatic colorectal cancer and its potential in other malignancies. Drugs 2000;60(4):895-924.
8. Graham MA, Lockwood GF, Greenslade D, et al. Clinical pharmacokinetics of oxaliplatin: a critical review. Clinical
Cancer Research 2000;6(4):1205-18.
9. Extra JM, Marty M, Brienza S, et al. Pharmacokinetics and safety profile of oxaliplatin. Seminars in Oncology 1998;25(2
Suppl 5):13-22.
10. Andre T, Bensmaine MA, Louvet C, et al. Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil
infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen. Journal
of Clinical Oncology 1999;17(11):3560-8.
11. de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment
in advanced colorectal cancer. Journal of Clinical Oncology 2000;18(16):2938-47.
12. Giacchetti S, Perpoint B, Zidani R, et al. Phase III multicenter randomized trial of oxaliplatin added to
chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. Journal of Clinical
Oncology 2000;18(1):136-47.
13. Cottu PH, Zelek L, Vannetzel J, et al. A phase II study of oxaliplatin (Oxa) and 5-fluorouracil (Fu) in
advanced/metastatic breast carcinoma (Abc) patients (Pts) previously treated with taxanes (t): Preliminary results.
Proceedings of the American Society of Clinical Oncology 2000;19:155a-abstract 609G.
14. Louvet C, Andre T, Tigaud J, et al. Phase II trial of oxaliplatin (OXA) in combination with 5FU and folinic acid (FA) -
FOLFOX6 regimen - as first-line treatment for advanced or metastatic gastric cancer (A/MGC) patients. Proceedings of
the American Society of Clinical Oncology 2000;19:265a-abstract 1031.
15. Soulie P, Garrino C, Bensmaine MA, et al. Antitumoral activity of oxaliplatin/cisplatin-based combination therapy in
cisplatin-refractory germ cell cancer patients. Journal of Cancer Research & Clinical Oncology 1999;125(12):707-11.
16. Degardin M, Cappelaere P, Krakowski I, et al. Phase II trial of oxaliplatin (L-OHP) in advanced, recurrent and/or
metastatic squamous cell carcinoma of the head and neck [letter]. European Journal of Cancer. Part B, Oral Oncology
1996;32B(4):278-9.
17. Monnet I, Brienza S, Hugret F, et al. Phase II study of oxaliplatin in poor-prognosis non-small cell lung cancer
(NSCLC). ATTIT. Association pour le Traitement des Tumeurs Intra Thoraciques. European Journal of Cancer
1998;34(7):1124-7.
18. Germann N, Brienza S, Rotarski M, et al. Preliminary results on the activity of oxaliplatin (L-OHP) in
refractory/recurrent non-Hodgkin's lymphoma patients. Annals of Oncology 1999;10(3):351-4.
19. Fizazi K, Caliandro R, Soulie P, et al. Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle
against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in
mesothelioma. European Journal of Cancer 2000;36(12):1514-21.
20. Fizazi K, Doubre H, Viala J, et al. The combination of raltitrexed ('Tomudex') and oxaliplatin is an active regimen in
malignant mesotherlioma: Results of a phase II study. Proceedings of the American Society of Clinical Oncology
2000;19:578a-abstract 2276.
21. Piccart MJ, Green JA, Lacave AJ, et al. Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian
cancer: A randomized phase II study of the European Organization for Research and Treatment of Cancer Gynecology
Group. Journal of Clinical Oncology 2000;18(6):1193-202.
22. Misset JL, Vennin P, Chollet P, et al. Multicenter phase II/III study of oxaliplatin plus cyclophophamide (C) [OXC]
versus cisplatin (P) plus cyclophosphamide (CPC) in advanced chemonaive ovarian cancer (AOC) patients (Pts): Final
results. Proceedings of the American Society of Clinical Oncology 2000;19:380a-abstract 1502.
23. Rougier P, Ducreux M, Ould Kaci M, et al. Randomized phase II study of oxaliplatin alone (OXA), 5-fluorouracil (5FU)
alone, and the two drugs combined (OXA-FU) in advanced or metastatic pancreatic adenocarcinoma (APC). Proceedings
of the American Society of Clinical Oncology 2000;19:262a-abstract 1018.
24. Droz JP, Muracciole X, Mottet N, et al. Phase II randomized study of oxaliplatin (OXA), and its combination with 5-FU
(OXA-FU) in hormone refractory prostate cancer (HRPC) patients (Pts) (Meeting abstract). Proceedings of the American
Society of Clinical Oncology 2000;19:359a (abstract 1415).
25. sanofi-aventis Canada Inc. ELOXATIN product monograph. Laval, Quebec; 13 March 2015.
26. FDA Medwatch. Safety labelling changes approved by FDA Center for Drug Evaluation and Research (CDER):
ELOXATIN (oxaliplatin) for intravenous use. FDA US Food and Drug Administration, October 2015. Available at:
http://www.fda.gov/Safety/MedWatch/default.htm. Accessed 29 December 2015.
27. Brienza S, Vignoud J, Itzhaki M, et al. Oxaliplatin (L-OHP): global safety in 682 patients (pts) (Meeting abstract).
Proceedings of the American Society of Clinical Oncology 1995;14:A513.
28. Tournigand C, Maindrault-Goebel F, Louvet C, et al. Severe anaphylactic reactions to oxaliplatin [letter]. European
Journal of Cancer 1998;34(8):1297-8.
29. Medioni J, Coulon MA, Morere JF, et al. Anaphylaxis after oxaliplatin [letter]. Annals of Oncology 1999;10(5):610.
30. Garufi C, Vaglio S, Brienza S, et al. Immunohemolytic anemia following oxaliplatin administration [letter]. Annals of
Oncology 2000;11(4):497.
31. Baur M, Kienzer HR, Rath T, et al. Extravasation of Oxaliplatin (Eloxatin((R))) - Clinical Course. Onkologie
2000;23(5):468-471.
32. Kennedy JG, Donahue JP, Hoang B, et al. Vesicant characteristics of oxaliplatin following antecubital extravasation.
Clin Oncol (R Coll Radiol) 2003;15(5):237-9.
33. Foo KF, Michael M, Toner G, et al. A case report of oxaliplatin extravasation. Ann Oncol 2003;14(6):961-2.
34. Eckert R, Maier KP. Necrotizing panniculitis after extravasation of oxaliplatin. Annals of Oncology 2002;13(Suppl 5):29
(abstract 103).
35. Kretzschmar A, Pink D, Thuss-Patience P, et al. Extravasations of oxaliplatin. J Clin Oncol 2003;21(21):4068-9.
36. Kretzschmar A, Thuss-Patience P, Pink D, et al. Extravasations of oxaliplatin. J Clin Oncol 2002;21:A2900.

BC Cancer Agency Cancer Drug Manual Page 7 of 9 Oxaliplatin
Developed: 2001
Revised: 1 December 2016
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37. BC 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
August 2014.
38. Extra JM, Espie M, Calvo F, et al. Phase I study of oxaliplatin in patients with advanced cancer. Cancer
Chemotherapy & Pharmacology 1990;25(4):299-303.
39. Kim HJ, An SH, Cho YH, et al. Oxaliplatin-induced Torsades de pointes and long QT syndrome in a patient with
gastric cancer. Acta Oncologica 2013;52(6):1223-1224.
40. Chung LW, Liao YM, Hsieh CY, et al. Oxaliplatin-induced long QT syndrome in a patient with appendiceal
adenocarcinoma. Acta Oncologica 2009;48(1):156-157.
41. Taieb S, Freyer G, Rambaud L, et al. Central neurotoxicity induced by oxaliplatin: Report on 4 cases. Proceedings of
the American Society of Clinical Oncology 2000;19:312a-abstract 1234.
42. Skelton MR, Golberg RM, O'Neil BH. A case of oxaliplatin-related posterior reversible encephalopathy syndrome. Clin
Colorectal Cancer 2007;6(5):386-388.
43. Sharief U, Perry DJ. Delayed reversible posterior encephalopathy syndrome following chemotherapy with oxaliplatin.
Clin Colorectal Cancer 2009;8(3):163-165.
44. Moris G, Ribacoba R, Gonzalez C. Delayed reversible posterior encephalopathy syndrome following chemotherapy
with oxaliplatin and gemcitabine. J Neurol 2007;254(4):534-535.
45. sanofi-aventis Canada Inc. ELOXATIN product monograph. Laval, Quebec; 17 September 2010.
46. sanofi-aventis Canada Inc. ELOXATIN product monograph. Laval, Quebec; 8 June 2011.
47. AHFS Drug Information (database on the Internet). Oxaliplatin. Lexi-Comp Inc., November 2009. Available at:
http://online.lexi.com. Accessed 5 March 2013.
48. Lexi-Drugs (database on the Internet). Oxaliplatin. Lexi-Comp Inc., 4 March 2013. Available at: http://online.lexi.com.
Accessed 5 March 2013.
49. Loprinzi CL, Qin R, Dakhil SR, et al. Phase III randomized, placebo-controlled, double-blind study of intravenous
calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol
2013;32(10):997-1005.
50. Hochster HS, Grothey A, Shpilsky A, et al. Effect of intravenous (IV) calcium and magnesium (Ca/Mg) versus placebo
on response to FOLFOX+bevacizumab (BEV) in the CONcePT trial. Proc Am Soc Clin Oncol Gastrointestinal Cancers
Symposium 2008:(abstract 280).
51. Nikcevich DA, Grothey A, Sloan JA, et al. Effect of intravenous calcium and magnesium (IV CaMg) on oxaliplatin-
induced sensory neurotoxicity (sNT) in adjuvant colon cancer: Results of the phase III placebo-controlled, double-blind
NCCTG trial N04C7. J Clin Oncol (Meeting Abstracts) 2008;26(15_suppl):4009.
52. Grothey A, Hart LL, Rowland KM, et al. Intermittent oxaliplatin (oxali) administration and time-to-treatment-failure
(TTF) in metastatic colorectal cancer (mCRC): Final results of the phase III CONcePT trial. J Clin Oncol (Meeting
Abstracts) 2008;26(15_suppl):4010.
53. Mariana G, Garrone O, Granetto C, et al. Oxaliplatin induced neuropathy: Could gabapentin be the answer?
Proceedings of the American Society of Clinical Oncology 2000;19:609a-abstract 2397.
54. Wilson RH, Lehky T, Thomas RR, et al. Acute Oxaliplatin-Induced Peripheral Nerve Hyperexcitability. J Clin Oncol
2002;20(7):1767-1774.
55. Gedlicka C, Scheithauer W, Schull B, et al. Effective Treatment of Oxaliplatin-Induced Cumulative Polyneuropathy
With Alpha-Lipoic Acid. J Clin Oncol 2002;20(15):3359-3361.
56. Pinedo DM, Shah-Khan F, Shah PC. Reversible posterior leukoencephalopathy syndrome associated with oxaliplatin.
J Clin Oncol 2007;25(33):5320-5321.
57. Stephen Doyle. Personal communication. Medical Marketing Manager - Oncology & Haematology; Sanofi~Synthelabo
Australia Pty Limited; 21 July 2004.
58. The National Extravasation Information Service. Protocol for management of chemotherapy extravasation. ; 6 January
2004.
59. Joel SP, Richards F, Seymour M. Oxaliplatin (L-OHP) does not influence the pharmacokinetics of 5-fluorouracil (5-
FU)(Abstract 748). Proc Am Soc Clin Oncol 2000;19:192a.
60. Valencak J, Raderer M, Kornek GV, et al. Irinotecan-related cholinergic syndrome induced by coadministration of
oxaliplatin [letter] [see comments]. Journal of the National Cancer Institute 1998;90(2):160.
61. Cvitkovic E, Marty M, Wasserman E, et al. Re: Irinotecan-related cholinergic syndrome induced by coadministration of
oxaliplatin [letter; comment]. Journal of the National Cancer Institute 1998;90(13):1016-7.
62. Dodds HM, Bishop JF, Rivory LP. More about: irinotecan-related cholinergic syndrome induced by coadministration of
oxaliplatin [letter; comment]. Journal of the National Cancer Institute 1999;91(1):91-2.
63. Lokiec F, Goldwasser F, Santoni J, et al. Pharmacokinetics (PK) of the oxaliplatin (LOHP)/topotecan (T) combination:
Preliminary data of an ongoing phase I trial (Meeting abstract). Proc Am Assoc Cancer Res 1999;40:82-abstract 548.
64. Masci G, Magagnoli M, Zucali PA, et al. Minidose warfarin prophylaxis for catheter-associated thrombosis in cancer
patients: can it be safely associated with fluorouracil-based chemotherapy? J Clin Oncol 2003;21(4):736-739.
65. Sandoz Canada Inc. Oxaliplatin injection product monograph. Boucherville, Quebec; 12 August 2015.
66. Sanofi-Synthelabo. ELOXATIN: Summary of product characteristics. August 2001.
67. Sanofi-Synthelabo. Eloxatin: Summary of product characteristics. Guildford, Surrey, United Kingdom; 13 December
2001.
68. Vassilaki M, Desses N, V P, et al. Two phase II studies with the combination of oxaliplatin (L-OHP) + 5-fluorouracil (5-
FU) + leucovorin (LV) as first line treatment in pts with metastatic colorectal cancer (MCC). Proceedings of the American
Society of Clinical Oncology 2000;19:284a-abstract 1111.
69. Elias D, Lefevre JH, Chevalier J, et al. Complete Cytoreductive Surgery Plus Intraperitoneal Chemohyperthermia With
Oxaliplatin for Peritoneal Carcinomatosis of Colorectal Origin. Journal of Clinical Oncology 2009;27(5):681-685.

BC Cancer Agency Cancer Drug Manual Page 8 of 9 Oxaliplatin
Developed: 2001
Revised: 1 December 2016
 Oxaliplatin

70. 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.
71. BC Cancer Agency Gastrointestinal Tumour Group. (GIHIPEC) BCCA Protocol Summary for Hyperthermic
Intraperitoneal Chemotherapy (HIPEC) for Patients with Peritoneal Carcinomatosis from Limited Advanced Colorectal and
Appendiceal Carcinomas Using Oxaliplatin and Fluorouracil (5-FU). Vancouver, British Columbia: BC Cancer Agency; I
November 2015.
72. Kern W, Beckert B, Lang N, et al. Phase I and pharmacokinetic study of hepatic arterial infusion with oxaliplatin, folinic
acid and 5-fluorouracil in patients with hepatic metastases from colorectal cancer. Proceedings of the American Society of
Clinical Oncology 2000;19:289a-abstract 1132.
73. Brienza S, Bensmaine MA, Soulie P, et al. Oxaliplatin added to 5-fluorouracil-based therapy (5-FU +/- FA) in the
treatment of 5-FU-pretreated patients with advanced colorectal carcinoma (ACRC): results from the European
compassionate-use program. Annals of Oncology 1999;10(11):1311-6.
74. Caussanel JP, Levi F, Brienza S, et al. Phase I trial of 5-day continuous venous infusion of oxaliplatin at circadian
rhythm-modulated rate compared with constant rate. Journal of the National Cancer Institute 1990;82(12):1046-50.
75. Giornelli G, Roca E, Chacon M, et al. Bimonthly oxaliplatin (L-OHP) and weekly bolus 5-fluorouracil and folinic acid
(FA) in patients (Pts) with metastatic colorectal cancer (CRC): A feasible and active regimen. Proceedings of the
American Society of Clinical Oncology 2000;19:295a.
76. Janinis J, Papakostas P, Samelis G, et al. Second-line chemotherapy with weekly oxaliplatin and high-dose 5-
fluorouracil with folinic acid in metastatic colorectal carcinoma: a Hellenic Cooperative Oncology Group (HeCOG) phase II
feasibility study. Annals of Oncology 2000;11(2):163-7.
77. Maindrault-Goebel F, Louvet C, Carola E, et al. Oxaliplatin reintroduction in patients pretreated with leucovorin (LV), 5-
FU and oxaliplatin for metastatic colorectal cancer. A Gercor study (Meeting abstract). Proceedings of the American
Society of Clinical Oncology 2000;19:255a-abstract 990.
78. Massari C, Brienza S, Rotarski M, et al. Pharmacokinetics of oxaliplatin in patients with normal versus impaired renal
function. Cancer Chemotherapy & Pharmacology 2000;45(2):157-64.

BC Cancer Agency Cancer Drug Manual Page 9 of 9 Oxaliplatin
Developed: 2001
Revised: 1 December 2016