Usual Adult Dose for Non-Small Cell Lung Cancer

IN COMBINATION WITH CISPLATIN:
25 mg/m2 IV over 6 to 10 minutes on Days 1, 8, 15, and 21 of a 28-day cycle in combination with cisplatin 100 mg/m2 IV on Day 1 only of each 28-day cycle
OR
30 mg/m2 IV over 6 to 10 minutes once a week in combination with cisplatin 120 mg/m2 IV on Days 1 and 29, then every 6 weeks

AS A SINGLE AGENT:
30 mg/m2 IV over 6 to 10 minutes once a week

Uses:

• In combination with cisplatin for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)
• As a single agent, for the treatment of patients with metastatic NSCLC

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

DOSE MODIFICATIONS FOR HEPATIC TOXICITY:

• See DOSE ADJUSTMENTS.
• The influence of hepatic impairment on the pharmacokinetics of this drug has not been evaluated, but the liver plays an important role in the metabolism of this drug. Elevations of aspartate aminotransferase occur in more than 60% of patients receiving this drug alone (6% Grade 3 or 4); therefore, exercise caution in patients with hepatic impairment. Reduce the dose of this drug for patients with bilirubin elevation.

Dose Adjustments

HEMATOLOGIC TOXICITY:
Hold or decrease the dose in patients with decreased neutrophil counts on the day of therapy using the following:

• For 1500 cells/mm3 or greater: Give 100% of the starting dose.
• For 1000 to 1499 cells/mm3: Give 50% of the starting dose.
• For less than 1000 cells/mm3: Do not administer this drug. Repeat neutrophil count in 1 week. If 3 consecutive weekly doses are held because neutrophil count in less than 1000 cells/mm3, discontinue therapy.

For patients who experience fever and/or sepsis while neutrophil count is less than 1500 cells/mm3 or had 2 consecutive weekly doses held due to neutropenia, subsequent doses of this drug should be:

• Greater than 1500 cells/mm3: Give 75% of dose
• For 1000 to 1499 cells/mm3: Give 37.5% of dose
• For less than 1000 cells/mm3: Do not administer this drug. Repeat neutrophil count in one week.

HEPATIC TOXICITY:
Patients with elevated serum total bilirubin concentration:

• Serum total bilirubin concentration 2 mg/dL or less: Give 100% of the starting dose.
• Serum total bilirubin concentration 2.1 to 3 mg/dL: Give 50% of the starting dose.
• Serum total bilirubin concentration greater than 3 mg/dL: Give 25% of the starting dose.

CONCURRENT HEMATOLOGIC TOXICITY AND HEPATIC IMPAIRMENT: In patients with both hematologic toxicity and hepatic impairment, administer the lower of the doses based on the corresponding starting dose of this drug determined from the dose modifications for hematologic toxicity and dose modifications for hepatic toxicity.

NEUROLOGIC TOXICITY: Discontinue this drug for NCI CTCAE Grade 2 or higher peripheral neuropathy or autonomic neuropathy causing constipation.

Precautions

US BOXED WARNINGS:

• Severe myelosuppression resulting in serious infection, septic shock, hospitalization and death may occur.

Recommendation:

• Decrease the dose or withhold therapy according to the recommended dose modifications.

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
IV FORMULATION:

• Administer the diluted IV solution over 6 to 10 minutes into the side port of a free-flowing IV line followed by flushing with at least 75 to 125 mL of one of the solutions.
• This drug should only be administered IV. It is extremely important that the IV needle or catheter be properly positioned before any drug is injected.
• Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. If particulate matter is seen, this drug should not be administered.

CAPSULE FORMULATION:

• If the patient chews or sucks the capsule by error, the liquid is an irritant. Rinse the mouth with water or a normal saline solution.
• If a capsule is cut or damaged, the liquid content is an irritant, and may cause damage to the skin, mucosa, or eyes.
• In the case of vomiting within a few hours after drug intake, do not readminister. Supportive treatment such as metoclopramide or 5HT3 antagonists (e.g., ondansetron, granisetron) may reduce the occurrence of vomiting.
• The soft capsule is associated with a higher incidence of nausea/vomiting than the IV formulation.
• Primary prophylaxis with antiemetics and administration of the capsules with some food is recommended to reduce the incidence of nausea and vomiting.

Storage requirements:

• IV formulation: Store the vials at 2C to 8C (36F to 46F) in the carton. Protect from light. Do not freeze. Unopened vials are stable at 25C (77F) for up to 72 hours. Diluted product may be used for up to 24 hours under normal room light when stored in polypropylene syringes or polyvinyl chloride bags at 5C to 30C (41F to 86F).
• Capsule formulation: Store refrigerated at 2C to 8C in the original container. Do not freeze). Protect from light.

Reconstitution/preparation techniques:

• The manufacturer product information should be consulted.

IV compatibility:
This drug is compatible with all the following solutions:
5% Dextrose Injection
0.9% Sodium Chloride Injection
0.45% Sodium Chloride Injection
5% Dextrose and 0.45% Sodium Chloride Injection
Ringer's Injection
Lactated Ringer's Injection

General:

• This drug should be prescribed by a physician who is experienced in the use of chemotherapy with facilities for monitoring cytotoxic drugs.
• Handle and dispose of this drug consistent with recommendations for the handling and disposal of hazardous drugs.
• Exercise caution in handling and preparing the IV solution. The use of gloves is recommended. If the solution contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water.
• Avoid contamination of the eye with this drug. If exposure occurs, flush the eyes with water immediately and thoroughly.

Monitoring:

• Hematologic
• Hepatic

Patient advice:

• Do not swallow damaged capsules. Return them to the pharmacy or to the doctor to be properly destroyed.
• Follow a diet rich in fiber, drink fluids to stay well hydrated, and use stool softeners to avoid constipation. Contact a health care provider for severe constipation, new onset abdominal pain, or nausea and vomiting.
• Contact a healthcare provider for new onset fever or symptoms of infection.
• Patients receiving concomitant morphine or opioid analgesics: laxatives and careful monitoring of bowel mobility are recommended. Prescription of laxatives may be appropriate in patients with prior history of constipation.