Dosage Form: injection, solution, concentrate
FULL PRESCRIBING INFORMATION
Anaphylactic reactions to Eloxatin have been reported, and may occur within minutes of Eloxatin administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms of anaphylaxis [see Warnings and Precautions (5.1)].
Indications and Usage for Eloxatin
Eloxatin, used in combination with infusional 5-fluorouracil/leucovorin, is indicated for:
- adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor.
- treatment of advanced colorectal cancer.
DOSAGE and ADMINISTRATION
Eloxatin (oxaliplatin injection) should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.
Dosage
Administer Eloxatin in combination with 5-fluorouracil/leucovorin every 2 weeks. For advanced disease, treatment is recommended until disease progression or unacceptable toxicity. For adjuvant use, treatment is recommended for a total of 6 months (12 cycles):
Day 1: Eloxatin 85 mg/m2 intravenous infusion in 250–500 mL 5% Dextrose injection, USP and leucovorin 200 mg/m2 intravenous infusion in 5% Dextrose Injection, USP both given over 120 minutes at the same time in separate bags using a Y-line, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2–4 minutes, followed by 5-fluorouracil 600 mg/m2 intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion.
Day 2: Leucovorin 200 mg/m2 intravenous infusion over 120 minutes, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2–4 minutes, followed by 5-fluorouracil 600 mg/m2 intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion.
Figure 1
The administration of Eloxatin does not require prehydration. Premedication with antiemetics, including 5-HT3 blockers with or without dexamethasone, is recommended.
For information on 5-fluorouracil and leucovorin, see the respective package inserts.
Dose Modification Recommendations
Prior to subsequent therapy cycles, patients should be evaluated for clinical toxicities and recommended laboratory tests [see Warnings and Precautions (5.6)]. Prolongation of infusion time for Eloxatin from 2 hours to 6 hours may mitigate acute toxicities. The infusion times for 5-fluorouracil and leucovorin do not need to be changed.
Adjuvant Therapy in Patients with Stage III Colon Cancer
Neuropathy and other toxicities were graded using the NCI CTC scale version 1 [see Warnings and Precautions (5.2)].
For patients who experience persistent Grade 2 neurosensory events that do not resolve, a dose reduction of Eloxatin to 75 mg/m2 should be considered. For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered. The infusional 5-fluorouracil/leucovorin regimen need not be altered.
A dose reduction of Eloxatin to 75 mg/m2 and infusional 5-fluorouracil to 300 mg/m2 bolus and 500 mg/m2 22 hour infusion is recommended for patients after recovery from grade 3/4 gastrointestinal (despite prophylactic treatment) or grade 4 neutropenia or grade 3/4 thrombocytopenia. The next dose should be delayed until: neutrophils ≥1.5 × 109/L and platelets ≥75 × 109/L.
Dose Modifications in Therapy in Previously Untreated and Previously Treated Patients with Advanced Colorectal Cancer
Neuropathy was graded using a study-specific neurotoxicity scale [see Warnings and Precautions (5.2)]. Other toxicities were graded by the NCI CTC, Version 2.0.
For patients who experience persistent Grade 2 neurosensory events that do not resolve, a dose reduction of Eloxatin to 65 mg/m2 should be considered. For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered. The 5-fluorouracil/leucovorin regimen need not be altered.
A dose reduction of Eloxatin to 65 mg/m2 and 5-fluorouracil by 20% (300 mg/m2 bolus and 500 mg/m2 22-hour infusion) is recommended for patients after recovery from grade 3/4 gastrointestinal (despite prophylactic treatment) or grade 4 neutropenia or grade 3/4 thrombocytopenia. The next dose should be delayed until: neutrophils ≥1.5 × 109/L and platelets ≥75 × 109/L.
Dose Modifications in Therapy for Patients with Renal Impairment
In patients with normal renal function or mild to moderate renal impairment, the recommended dose of Eloxatin is 85 mg/m2. In patients with severe renal impairment, the initial recommended Eloxatin dose should be reduced to 65 mg/m2 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Preparation of Infusion Solution
Powder for solution for infusion
Reconstitution or final dilution must never be performed with a sodium chloride solution or other chloride containing solutions.
The lyophilized powder is reconstituted by adding 10 mL (for the 50 mg vial) or 20 mL (for the 100 mg vial) of Water for Injection, USP or 5% Dextrose Injection, USP. Do not administer the reconstituted solution without further dilution. The reconstituted solution must be further diluted in an infusion solution of 250–500 mL of 5% Dextrose Injection, USP.
After reconstitution in the original vial, the solution may be stored up to 24 hours under refrigeration [2–8°C (36–46°F)]. After final dilution with 250–500 mL of 5% Dextrose Injection, USP, the shelf life is 6 hours at room temperature [20–25°C (68–77°F)] or up to 24 hours under refrigeration [2–8°C (36–46°F)].
Eloxatin is not light sensitive.
Concentrate for solution for infusion
Do not freeze and protect from light the concentrated solution.
A final dilution must never be performed with a sodium chloride solution or other chloride-containing solutions.
The solution must be further diluted in an infusion solution of 250-500 mL of 5% Dextrose Injection, USP.
After dilution with 250-500 mL of 5% Dextrose Injection, USP, the shelf life is 6 hours at room temperature [20-25°C (68-77°F)] or up to 24 hours under refrigeration [2-8°C (36-46°F)].
After final dilution, protection from light is not required.
Eloxatin is incompatible in solution with alkaline medications or media (such as basic solutions of 5-fluorouracil) and must not be mixed with these or administered simultaneously through the same infusion line. The infusion line should be flushed with 5% Dextrose Injection, USP prior to administration of any concomitant medication.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration and discarded if present.
Needles or intravenous administration sets containing aluminum parts that may come in contact with Eloxatin should not be used for the preparation or mixing of the drug. Aluminum has been reported to cause degradation of platinum compounds.
Dosage Forms and Strengths
Eloxatin is supplied in single-use vials containing 50 mg or 100 mg of oxaliplatin as a sterile, preservative-free lyophilized powder for reconstitution.
Eloxatin is supplied in single-use vials containing 50 mg, 100 mg or 200 mg of oxaliplatin as a sterile, preservative-free, aqueous solution at a concentration of 5 mg/ml.
Contraindications
Eloxatin should not be administered to patients with a history of known allergy to Eloxatin or other platinum compounds [see Warnings and Precautions (5.1)].
Warnings and Precautions
Allergic Reactions
See boxed warning
Grade 3/4 hypersensitivity, including anaphylactic/anaphylactoid reactions, to Eloxatin has been observed in 2–3% of colon cancer patients. These allergic reactions which can be fatal, can occur within minutes of administration and at any cycle, and were similar in nature and severity to those reported with other platinum-containing compounds, such as rash, urticaria, erythema, pruritus, and, rarely, bronchospasm and hypotension. The symptoms associated with hypersensitivity reactions reported in the previously untreated patients were urticaria, pruritus, flushing of the face, diarrhea associated with oxaliplatin infusion, shortness of breath, bronchospasm, diaphoresis, chest pains, hypotension, disorientation and syncope. These reactions are usually managed with standard epinephrine, corticosteroid, antihistamine therapy, and require discontinuation of therapy. Rechallenge is contraindicated in these patients [see Contraindications (4)]. Drug-related deaths associated with platinum compounds from anaphylaxis have been reported.
Neurologic Toxicity
Neuropathy
Eloxatin is associated with two types of neuropathy:
An acute, reversible, primarily peripheral, sensory neuropathy that is of early onset, occurring within hours or one to two days of dosing, that resolves within 14 days, and that frequently recurs with further dosing.The symptoms may be precipitated or exacerbated by exposure to cold temperature or cold objects and they usually present as transient paresthesia, dysesthesia and hypoesthesia in the hands, feet, perioral area, or throat. Jaw spasm, abnormal tongue sensation, dysarthria, eye pain, and a feeling of chest pressure have also been observed. The acute, reversible pattern of sensory neuropathy was observed in about 56% of study patients who received Eloxatin with 5-fluorouracil/leucovorin. In any individual cycle acute neurotoxicity was observed in approximately 30% of patients. In adjuvant patients the median cycle of onset for grade 3 peripheral sensory neuropathy was 9 in the previously treated patients the median number of cycles administered on the Eloxatin with 5-fluorouracil/leucovorin combination arm was 6.
An acute syndrome of pharyngolaryngeal dysesthesia seen in 1–2% (grade 3/4) of patients previously untreated for advanced colorectal cancer, and the previously treated patients, is characterized by subjective sensations of dysphagia or dyspnea, without any laryngospasm or bronchospasm (no stridor or wheezing). Ice (mucositis prophylaxis) should be avoided during the infusion of Eloxatin because cold temperature can exacerbate acute neurological symptoms.
A persistent (>14 days), primarily peripheral, sensory neuropathy that is usually characterized by paresthesias, dysesthesias, hypoesthesias, but may also include deficits in proprioception that can interfere with daily activities (e.g., writing, buttoning, swallowing, and difficulty walking from impaired proprioception). These forms of neuropathy occurred in 48% of the study patients receiving Eloxatin with 5-fluorouracil/leucovorin. Persistent neuropathy can occur without any prior acute neuropathy event. The majority of the patients (80%) who developed grade 3 persistent neuropathy progressed from prior Grade 1 or 2 events. These symptoms may improve in some patients upon discontinuation of Eloxatin.
In the adjuvant colon cancer trial, neuropathy was graded using a prelisted module derived from the Neuro-Sensory section of the National Cancer Institute Common Toxicity Criteria (NCI CTC) scale, Version 1, as follows:
| Grade | Definition |
|---|---|
| Grade 0 | No change or none |
| Grade 1 | Mild paresthesias, loss of deep tendon reflexes |
| Grade 2 | Mild or moderate objective sensory loss, moderate paresthesias |
| Grade 3 | Severe objective sensory loss or paresthesias that interfere with function |
| Grade 4 | Not applicable |
Peripheral sensory neuropathy was reported in adjuvant patients treated with the Eloxatin combination with a frequency of 92% (all grades) and 13% (grade 3). At the 28-day follow-up after the last treatment cycle, 60% of all patients had any grade (Grade 1=40%, Grade 2=16%, Grade 3=5%) peripheral sensory neuropathy decreasing to 39% at 6 months follow-up (Grade 1=31%, Grade 2=7%, Grade 3=1%) and 21% at 18 months of follow-up (Grade 1=17%, Grade 2=3%, Grade 3=1%).
In the advanced colorectal cancer studies, neuropathy was graded using a study-specific neurotoxicity scale, which was different from the NCI CTC scale, Version 2.0 (see below).
| Grade | Definition |
|---|---|
| Grade 1 | Resolved and did not interfere with functioning |
| Grade 2 | Interfered with function but not daily activities |
| Grade 3 | Pain or functional impairment that interfered with daily activities |
| Grade 4 | Persistent impairment that is disabling or life-threatening |
Overall, neuropathy was reported in patients previously untreated for advanced colorectal cancer in 82% (all grades) and 19% (grade 3/4), and in the previously treated patients in 74% (all grades) and 7% (grade 3/4) events. Information regarding reversibility of neuropathy was not available from the trial for patients who had not been previously treated for colorectal cancer.
Reversible Posterior Leukoencephalopathy Syndrome
Reversible Posterior Leukoencephalopathy Syndrome (RPLS, also known as PRES, Posterior Reversible Encephalopathy Syndrome) has been observed in clinical trials (< 0.1%) and postmarketing experience. Signs and symptoms of RPLS could be headache, altered mental functioning, seizures, abnormal vision from blurriness to blindness, associated or not with hypertension [see Adverse Reactions (6.2)]. Diagnosis of RPLS is based upon confirmation by brain imaging.
Pulmonary Toxicity
Eloxatin has been associated with pulmonary fibrosis (<1% of study patients), which may be fatal. The combined incidence of cough and dyspnea was 7.4% (any grade) and <1% (grade 3) with no grade 4 events in the Eloxatin plus infusional 5-fluorouracil/leucovorin arm compared to 4.5% (any grade) and no grade 3 and 0.1% grade 4 events in the infusional 5-fluorouracil/leucovorin alone arm in adjuvant colon cancer patients. In this study, one patient died from eosinophilic pneumonia in the Eloxatin combination arm. The combined incidence of cough, dyspnea and hypoxia was 43% (any grade) and 7% (grade 3 and 4) in the Eloxatin plus 5-fluorouracil/leucovorin arm compared to 32% (any grade) and 5% (grade 3 and 4) in the irinotecan plus 5-fluorouracil/leucovorin arm of unknown duration for patients with previously untreated colorectal cancer. In case of unexplained respiratory symptoms such as non-productive cough, dyspnea, crackles, or radiological pulmonary infiltrates, Eloxatin should be discontinued until further pulmonary investigation excludes interstitial lung disease or pulmonary fibrosis.
Hepatotoxicity
Hepatotoxicity as evidenced in the adjuvant study, by increase in transaminases (57% vs. 34%) and alkaline phosphatase (42% vs. 20%) was observed more commonly in the Eloxatin combination arm than in the control arm. The incidence of increased bilirubin was similar on both arms. Changes noted on liver biopsies include: peliosis, nodular regenerative hyperplasia or sinusoidal alterations, perisinusoidal fibrosis, and veno-occlusive lesions. Hepatic vascular disorders should be considered, and if appropriate, should be investigated in case of abnormal liver function test results or portal hypertension, which cannot be explained by liver metastases [see Clinical Trials Experience (6.1)].
Use in Pregnancy
Pregnancy Category D
Eloxatin may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Eloxatin in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Eloxatin. [see Use in Specific Populations (8.1)].
Recommended Laboratory Tests
Standard monitoring of the white blood cell count with differential, hemoglobin, platelet count, and blood chemistries (including ALT, AST, bilirubin and creatinine) is recommended before each Eloxatin cycle [see Dosage and Administration (2)].
There have been reports while on study and from post-marketing surveillance of prolonged prothrombin time and INR occasionally associated with hemorrhage in patients who received Eloxatin plus 5-fluorouracil/leucovorin while on anticoagulants. Patients receiving Eloxatin plus 5-fluorouracil/leucovorin and requiring oral anticoagulants may require closer monitoring.
Adverse Reactions
Clinical Trials Experience
Serious adverse reactions including anaphylaxis and allergic reactions, neuropathy, pulmonary toxicities and hepatotoxicities can occur [See Warnings and Precautions (5.1)].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
More than 1100 patients with stage II or III colon cancer and more than 4,000 patients with advanced colorectal cancer have been treated in clinical studies with Eloxatin. The most common adverse reactions in patients with stage II or III colon cancer receiving adjuvant therapy were peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue and stomatitis. The most common adverse reactions in previously untreated and treated patients were peripheral sensory neuropathies, fatigue, neutropenia, nausea, emesis, and diarrhea [see Warnings and Precautions (5)].
Combination Adjuvant Therapy with Eloxatin and Infusional 5-fluorouracil/leucovorin in Patients with Colon Cancer
One thousand one hundred and eight patients with stage II or III colon cancer, who had undergone complete resection of the primary tumor, have been treated in a clinical study with Eloxatin in combination with infusional 5-fluorouracil/leucovorin [see Clinical Studies (14)]. The incidence of grade 3 or 4 adverse reactions was 70% on the Eloxatin combination arm, and 31% on the infusional 5-fluorouracil/leucovorin arm. The adverse reactions in this trial are shown in the tables below. Discontinuation of treatment due to adverse reactions occurred in 15% of the patients receiving Eloxatin and infusional 5-fluorouracil/leucovorin. Both 5-fluorouracil/leucovorin and Eloxatin are associated with gastrointestinal or hematologic adverse reactions. When Eloxatin is administered in combination with infusional 5-fluorouracil/leucovorin, the incidence of these events is increased.
The incidence of death within 28 days of last treatment, regardless of causality, was 0.5% (n=6) in both the Eloxatin combination and infusional 5-fluorouracil/leucovorin arms, respectively. Deaths within 60 days from initiation of therapy were 0.3% (n=3) in both the Eloxatin combination and infusional 5-fluorouracil/leucovorin arms, respectively. On the Eloxatin combination arm, 3 deaths were due to sepsis/neutropenic sepsis, 2 from intracerebral bleeding and one from eosinophilic pneumonia. On the 5-fluorouracil/leucovorin arm, one death was due to suicide, 2 from Steven-Johnson Syndrome (1 patient also had sepsis), 1 unknown cause, 1 anoxic cerebral infarction and 1 probable abdominal aorta rupture.
The following table provides adverse reactions reported in the adjuvant therapy colon cancer clinical trial [see Clinical Studies (14)] by body system and decreasing order of frequency in the Eloxatin and infusional 5-fluorouracil/leucovorin arm for events with overall incidences ≥ 5% and for NCI grade 3/4 events with incidences ≥ 1%.
| Eloxatin + 5-FU/LV N=1108 | 5-FU/LV N=1111 | |||
|---|---|---|---|---|
| Adverse reaction (WHO/Pref) | All Grades (%) | Grade 3/4 (%) | All Grades (%) | Grade 3/4 (%) |
| ||||
| Any Event | 100 | 70 | 99 | 31 |
| Allergy/Immunology | ||||
| Allergic Reaction | 10 | 3 | 2 | <1 |
| Constitutional Symptoms/Pain | ||||
| Fatigue | 44 | 4 | 38 | 1 |
| Abdominal Pain | 18 | 1 | 17 | 2 |
| Dermatology/Skin | ||||
| Skin Disorder | 32 | 2 | 36 | 2 |
| Injection Site Reaction* | 11 | 3 | 10 | 3 |
| Gastrointestinal | ||||
| Nausea | 74 | 5 | 61 | 2 |
| Diarrhea | 56 | 11 | 48 | 7 |
| Vomiting | 47 | 6 | 24 | 1 |
| Stomatitis | 42 | 3 | 40 | 2 |
| Anorexia | 13 | 1 | 8 | <1 |
| Fever/Infection | ||||
| Fever | 27 | 1 | 12 | 1 |
| Infection | 25 | 4 | 25 | 3 |
| Neurology | ||||
| Overall Peripheral Sensory Neuropathy | 92 | 12 | 16 | <1 |
The following table provides adverse reactions reported in the adjuvant therapy colon cancer clinical trial [see Clinical Studies (14)] by body system and decreasing order of frequency in the Eloxatin and infusional 5-fluorouracil/leucovorin arm for events with overall incidences ≥ 5% but with incidences <1% NCI grade 3/4 events.
| Eloxatin + 5-FU/LV N=1108 | 5-FU/LV N=1111 | |
|---|---|---|
| Adverse reaction (WHO/Pref) | All Grades (%) | All Grades (%) |
| Allergy/Immunology | ||
| Rhinitis | 6 | 8 |
| Constitutional Symptoms/Pain/Ocular/Visual | ||
| Epistaxis | 16 | 12 |
| Weight Increase | 10 | 10 |
| Conjunctivitis | 9 | 15 |
| Headache | 7 | 5 |
| Dyspnea | 5 | 3 |
| Pain | 5 | 5 |
| Lacrimation Abnormal | 4 | 12 |
| Dermatology/Skin | ||
| Alopecia | 30 | 28 |
| Gastrointestinal | ||
| Constipation | 22 | 19 |
| Taste Perversion | 12 | 8 |
| Dyspepsia | 8 | 5 |
| Metabolic | ||
| Phosphate Alkaline increased | 42 | 20 |
| Neurology | ||
| Sensory Disturbance | 8 | 1 |
Although specific events can vary, the overall frequency of adverse reactions was similar in men and women and in patients <65 and ≥65 years. However, the following grade 3/4 events were more common in females: diarrhea, fatigue, granulocytopenia, nausea and vomiting. In patients ≥65 years old, the incidence of grade 3/4 diarrhea and granulocytopenia was higher than in younger patients. Insufficient subgroup sizes prevented analysis of safety by race. The following additional adverse reactions, were reported in ≥2% and <5% of the patients in the Eloxatin and infusional 5-fluorouracil/leucovorin combination arm (listed in decreasing order of frequency): pain, leukopenia, weight decrease, coughing.
The number of patients who developed secondary malignancies was similar; 62 in the Eloxatin combination arm and 68 in the infusional 5-fluorouracil/leucovorin arm. An exploratory analysis showed that the number of deaths due to secondary malignancies was 1.96% in the Eloxatin combination arm and 0.98% in infusional 5-fluorouracil/leucovorin arm. In addition, the number of cardiovascular deaths was 1.4% in the Eloxatin combination arm as compared to 0.7% in the infusional 5-fluorouracil/leucovorin arm. Clinical significance of these findings is unknown.
Patients Previously Untreated for Advanced Colorectal Cancer
Two hundred and fifty-nine patients were treated in the Eloxatin and 5-fluorouracil/leucovorin combination arm of the randomized trial in patients previously untreated for advanced colorectal cancer [see Clinical Studies (14)]. The adverse reaction profile in this study was similar to that seen in other studies and the adverse reactions in this trial are shown in the tables below.
Both 5-fluorouracil and Eloxatin are associated with gastrointestinal and hematologic adverse reactions. When Eloxatin is administered in combination with 5-fluorouracil, the incidence of these events is increased.
The incidence of death within 30 days of treatment in the previously untreated for advanced colorectal cancer study, regardless of causality, was 3% with the Eloxatin and 5-fluorouracil/leucovorin combination, 5% with irinotecan plus 5-fluorouracil/leucovorin, and 3% with Eloxatin plus irinotecan. Deaths within 60 days from initiation of therapy were 2.3% with the Eloxatin and 5-fluorouracil/leucovorin combination, 5.1% with irinotecan plus 5-fluorouracil/leucovorin, and 3.1% with Eloxatin plus irinotecan.
The following table provides adverse reactions reported in the previously untreated for advanced colorectal cancer study [see Clinical Studies (14)] by body system and decreasing order of frequency in the Eloxatin and 5-fluorouracil/leucovorin combination arm for events with overall incidences ≥5% and for grade 3/4 events with incidences ≥1%.
| Eloxatin + 5-FU/LV N=259 | irinotecan + 5-FU/LV N=256 | Eloxatin + irinotecan N=258 | ||||
|---|---|---|---|---|---|---|
| Adverse reaction (WHO/Pref) | All Grades (%) | Grade 3/4 (%) | All Grades (%) | Grade 3/4 (%) | All Grades (%) | Grade 3/4 (%) |
| ||||||
| Any Event | 99 | 82 | 98 | 70 | 99 | 76 |
| Allergy/Immunology | ||||||
| Hypersensitivity | 12 | 2 | 5 | 0 | 6 | 1 |
| Cardiovascular | ||||||
| Thrombosis | 6 | 5 | 6 | 6 | 3 | 3 |
| Hypotension | 5 | 3 | 6 | 3 | 4 | 3 |
| Constitutional Symptoms/Pain/Ocular/Visual | ||||||
| Fatigue | 70 | 7 | 58 | 11 | 66 | 16 |
| Abdominal Pain | 29 | 8 | 31 | 7 | 39 | 10 |
| Myalgia | 14 | 2 | 6 | 0 | 9 | 2 |
| Pain | 7 | 1 | 5 | 1 | 6 | 1 |
| Vision abnormal | 5 | 0 | 2 | 1 | 6 | 1 |
| Neuralgia | 5 | 0 | 0 | 0 | 2 | 1 |
| Dermatology/Skin | ||||||
| Skin reaction – hand/foot | 7 | 1 | 2 | 1 | 1 | 0 |
| Injection site reaction | 6 | 0 | 1 | 0 | 4 | 1 |
| Gastrointestinal | ||||||
| Nausea | 71 | 6 | 67 | 15 | 83 | 19 |
| Diarrhea | 56 | 12 | 65 | 29 | 76 | 25 |
| Vomiting | 41 | 4 | 43 | 13 | 64 | 23 |
| Stomatitis | 38 | 0 | 25 | 1 | 19 | 1 |
| Anorexia | 35 | 2 | 25 | 4 | 27 | 5 |
| Constipation | 32 | 4 | 27 | 2 | 21 | 2 |
| Diarrhea-colostomy | 13 | 2 | 16 | 7 | 16 | 3 |
| Gastrointestinal NOS* | 5 | 2 | 4 | 2 | 3 | 2 |
| Hematology/Infection | ||||||
| Infection normal ANC† | 10 | 4 | 5 | 1 | 7 | 2 |
| Infection low ANC† | 8 | 8 | 12 | 11 | 9 | 8 |
| Lymphopenia | 6 | 2 | 4 | 1 | 5 | 2 |
| Febrile neutropenia | 4 | 4 | 15 | 14 | 12 | 11 |
| Hepatic/Metabolic/Laboratory/Renal | ||||||
| Hyperglycemia | 14 | 2 | 11 | 3 | 12 | 3 |
| Hypokalemia | 11 | 3 | 7 | 4 | 6 | 2 |
| Dehydration | 9 | 5 | 16 | 11 | 14 | 7 |
| Hypoalbuminemia | 8 | 0 | 5 | 2 | 9 | 1 |
| Hyponatremia | 8 | 2 | 7 | 4 | 4 | 1 |
| Urinary frequency | 5 | 1 | 2 | 1 | 3 | 1 |
| Neurology | ||||||
| Overall Neuropathy | 82 | 19 | 18 | 2 | 69 | 7 |
| Paresthesias | 77 | 18 | 16 | 2 | 62 | 6 |
| Pharyngo-laryngeal dysesthesias | 38 | 2 | 1 | 0 | 28 | 1 |
| Neuro-sensory | 12 | 1 | 2 | 0 | 9 | 1 |
| Neuro NOS* | 1 | 0 | 1 | 0 | 1 | 0 |
| Pulmonary | ||||||
| Cough | 35 | 1 | 25 | 2 | 17 | 1 |
| Dyspnea | 18 | 7 | 14 | 3 | 11 | 2 |
| Hiccups | 5 | 1 | 2 | 0 | 3 | 2 |
The following table provides adverse reactions reported in the previously untreated for advanced colorectal cancer study [see Clinical Studies (14)] by body system and decreasing order of frequency in the Eloxatin and 5-fluorouracil/leucovorin combination arm for events with overall incidences ≥5% but with incidences <1% NCI Grade 3/4 events.
| Eloxatin + 5-FU/LV N=259 | irinotecan + 5-FU/LV N=256 | Eloxatin + irinotecan N=258 | |
|---|---|---|---|
| Adverse reaction (WHO/Pref) | All Grades (%) | All Grades (%) | All Grades (%) |
| |||
| Allergy/Immunology | |||
| Rash | 11 | 4 | 7 |
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