Usual Adult Dose for Ovarian Cancer

1.5 mg/m(2) IV over 30 minutes once a day for 5 consecutive days, starting on day 1 of a 21 day course

Comments:

• In the absence of tumor progression, a minimum of 4 courses is recommended because tumor response may be delayed.
• The median time to response was 9 to 12 weeks.
• Recommended dosage should generally not exceed 4 mg.

Use: Metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Usual Adult Dose for Cervical Cancer

0.75 mg/m(2) IV over 30 minutes on days 1, 2, and 3 of each 21 day cycle

Comments:

• Administer cisplatin 50 mg/m(2) IV on day 1 of each 21 day cycle.
• Consult cisplatin manufacturer product information for administration and hydration guidelines, and for dose adjustments.
• Recommended dosage should generally not exceed 4 mg.

Use: In combination with cisplatin, treatment of stage IVB, recurrent or persistent carcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.

Usual Adult Dose for Small Cell Lung Cancer

IV formulation: 1.5 mg/m(2) IV over 30 minutes once a day for 5 consecutive days, starting on day 1 of a 21 day course
Oral capsules: 2.3 mg/m(2) orally once a day for 5 consecutive days, starting on day 1 of a 21 day course (round dose to nearest 0.25 mg)

Duration of therapy: Until disease progression

Comments:

• In the absence of tumor progression, a minimum of 4 courses is recommended because tumor response may be delayed.
• The median time to response was 5 to 7 weeks.
• Recommended IV dosage should generally not exceed 4 mg.
• Do not prescribe a replacement oral capsule dose for emesis.

Uses:
IV formulation: Small cell lung cancer sensitive disease after failure of first-line chemotherapy. Sensitive disease was defined as disease responding to chemotherapy but subsequently progressing at least 60 to 90 days after chemotherapy.
Capsule formulation: Treatment of relapsed small cell lung cancer in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy.

Renal Dose Adjustments

Small cell lung cancer or Ovarian cancer, IV formulation:

• Mild renal impairment (CrCl 40 to 60 mL/min): No adjustment recommended
• Moderate renal impairment (CrCl 20 to 39 mL/min): Decrease dose to 0.75 mg/m(2)
• Severe renal impairment: Insufficient data to provide a dosage recommendation

Small cell lung cancer, oral capsules:

• Mild renal impairment (CrCl 50 to 79 mL/min): No adjustment recommended
• Moderate renal impairment (CrCl 30 to 49 mL/min): Decrease dose to 1.5 mg/m(2)
• Severe renal impairment (CrCl less than 30): Decrease dose to 0.6 mg/m(2)
• Doses for moderate to severe renal impairment can be increased by 0.4 mg/m(2) after the first course if no severe hematologic or gastrointestinal toxicities occur.

Cervical cancer:

• Only initiate treatment if serum creatinine is less than 1.5 mg/dL
• Serum creatinine greater than 1.5 mg/dL on day 1 of first cycle: Delay initiation of treatment until renal recovery
• Serum creatinine greater than 1.5 mg/dL on day 1 of subsequent cycles: Delay cycle until renal recovery
• Serum creatinine greater than 1.5 mg/dL in subsequent cycles: Permanently discontinue

Liver Dose Adjustments

Data not available

Dose Adjustments

All cancer types:
On day 1 of first cycle, delay therapy initiation until hematologic or renal recovery IF:

• Neutrophil count is less than 1,500 cells/mm(3) OR
• Platelet count 100,000 cells/mm(3) or less OR
• Serum creatinine less than 1.5 mg/dL

On day 1 of subsequent cycles, delay treatment cycle until hematologic or renal recovery IF:

• Neutrophil count is less than 1000 cells/mm(3) OR
• Platelet count 100,000 cells/mm(3) or less OR
• Serum creatinine less than 1.5 mg/dL OR
• Hemoglobin less than 9 gm/dL

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Small cell lung cancer or Ovarian cancer:
IV formulation:
Severe neutropenia [less than 500 cells/mm(3)] in preceding cycle:

• Permanently reduce IV dose by 0.25 mg [to 1.25 mg/m(2)] or oral dose by 0.4 mg/m(2) for subsequent courses OR
• Administer granulocyte-colony stimulating factor (G-CSF) following the subsequent course (before resorting to dose reduction) starting from day 6 of the course (24 hours after completion of topotecan administration).

Platelet count below 25,000 cells/mm(3): Reduce dose to 1.25 mg/m(2) for subsequent courses .

Oral capsules (Small cell lung cancer only):
Permanently reduce dose by 0.4 mg/m(2) for subsequent courses for:

• Neutrophil counts less than 500 cells/mm(3)] with fever or infection lasting 7 or more days
• Neutrophil counts of 500 to 1,000 cells/mm(3) lasting beyond day 21 of treatment course
• Platelet count below 25,000 cells/mm(3)

Do not give oral formulation to patients with Grade 3 or 4 diarrhea

• After recovery to Grade 1 or less, reduce dose by 0.4 mg/m(2) for subsequent courses

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Cervical cancer:
First occurrence of febrile neutropenia [less than 1,000 neutrophils/mm(3) with fever of 38 C/100.4F or higher] in preceding cycle:

• Permanently reduce dose to 0.60 mg/m(2) OR
• Administer prophylactic G-CSF during subsequent cycles

Re-occurrence of febrile neutropenia in preceding cycle despite use of G-CSF:

• Permanently reduce dose to 0.45 mg/m(2)

Platelet nadir less than 25,000 cells/mm(3) in preceding cycle:

• Permanently reduce dose to 0.60 mg/m(2)

Serum creatinine greater than 1.5 mg/dL in subsequent cycles:

• Permanently discontinue topotecan

Precautions

US BOXED WARNING:
BONE MARROW SUPPRESSION

• Bone marrow suppression, primarily neutropenia, may be severe and result in infection and death.
• Do not initiate treatment in patients with bone marrow suppression (e.g. neutrophil counts less than 1,500 cells/mm(3).
• Monitor peripheral blood counts frequently during treatment.
• Reduce or withhold treatment dosing as recommended.

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:

• Verify dose using body surface area.
• Oral capsules should be swallowed whole: do not crush, chew, or divide the capsules.
• Oral capsules can be taken with or without food.

Reconstitution/preparation techniques:

• Prepare in a laminar flow hood while wearing gloves and protective clothing.
• If solution contacts skin, wash skin immediately and thoroughly with soap and water.
• If solution contacts mucous membranes, flush thoroughly with water.