Important Safety Information
Indications
Hycamtin is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.
Hycamtin is indicated for the treatment of small cell lung cancer sensitive disease after failure of first-line chemotherapy.*
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*In clinical studies submitted to support approval, sensitive disease was defined as disease responding to chemotherapy but subsequently progressing ≥60 days (in the phase III study) or ≥90 days (in the phase II studies) after chemotherapy. |
Hycamtin in combination with cisplatin is indicated for the treatment of histologically confirmed Stage IV-B, recurrent, or persistent carcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
Contraindications
Hycamtin is contraindicated in patients who have a history of hypersensitivity reactions to topotecan or to any of its ingredients. Hycamtin should not be used in patients who are pregnant or breast-feeding, or those with severe bone marrow depression.
Warnings
Hycamtin should be used only in patients with adequate bone marrow reserves, including baseline neutrophil counts of at least 1,500 cells/mm³ and platelet counts of at least 100,000/mm³. Frequent monitoring of blood counts should be instituted during treatment with Hycamtin.
Patients should not be treated with subsequent courses of Hycamtin until neutrophils recover to >1,000 cells/mm³, platelets recover to >100,000 cells/mm³, and hemoglobin levels recover to 9.0 g/dL (with transfusion if necessary). Severe myelotoxicity has been reported when 5-day dosing of Hycamtin is used in combination with cisplatin.
Hycamtin may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Hycamtin.
Drug Interactions
Concomitant administration of G-CSF can prolong the duration of neutropenia, so if G-CSF is to be used, it should not be initiated until 24 hours after completion of treatment with Hycamtin.
Myelosuppression was more severe when Hycamtin, at a dose of 1.25 mg/m²/day x 5 days, was given in combination with cisplatin at a dose of 50 mg/m² in phase I studies. In one study, 1 of 3 patients had severe neutropenia for 12 days, and a second patient died with neutropenic sepsis.
Dosing for Ovarian Cancer/Small Cell Lung Cancer
Prior to administration of the first course of Hycamtin, patients must have a baseline neutrophil count of >1,500 cells/mm³ and a platelet count of >100,000 cells/mm³. The recommended dose of Hycamtin is 1.5 mg/m² by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on day 1 of a 21-day course.
In the absence of tumor progression, a minimum of 4 courses is recommended because tumor response may be delayed. The median time to response in 3 ovarian clinical trials was 9 to 12 weeks, and median time to response in 4 small cell lung cancer trials was 5 to 7 weeks.
In the event of severe neutropenia during any course, the dose should be reduced by 0.25 mg/m² (to 1.25 mg/m²) for subsequent courses. Doses should be similarly reduced if the platelet count falls below 25,000 cells/mm³. Alternatively, in the event of severe neutropenia, G-CSF may be administered following the subsequent course (before resorting to dose reduction) starting from 24 hours after completion of administration of Hycamtin.
Dosing for Cervical Cancer
Prior to administration of the first course of Hycamtin, patients must have a baseline absolute neutrophil count of >1,500 cells/mm³ and a platelet count of >100,000 cells/mm³. The recommended dose of Hycamtin is 0.75 mg/m² by intravenous infusion over 30 minutes daily on days 1, 2, and 3; followed by cisplatin 50 mg/m² by intravenous infusion on day 1 repeated every 21 days (a 21-day course).
Dosage adjustments for subsequent courses of a regimen of Hycamtin in combination with cisplatin are specific for each drug.
In the event of severe febrile neutropenia (defined as <1,000 cells/mm³ with temperature of 38.0°C or 100.4°F), the dose of Hycamtin should be reduced by 20% to 0.60 mg/m² for subsequent courses. Doses of Hycamtin should be similarly reduced (by 20% to 0.60 mg/m²) if the platelet count falls below 10,000 cells/mm³. Alternatively, in the event of severe febrile neutropenia, G-CSF may be administered following the subsequent course (before resorting to dose reduction) starting from day 4 of the course (24 hours after completion of topotecan administration). If febrile neutropenia occurs despite the use of G-CSF, the dose of Hycamtin should be reduced by another 20% to 0.45 mg/m² for subsequent courses.
Adverse Events for Ovarian Cancer/Small Cell Lung Cancer
The most common serious adverse event is myelosuppression.
Severe neutropenia, the dose-limiting toxicity for Hycamtin, occurred in 78% of 879 ovarian and small cell lung cancer patients treated. Other hematologic adverse events reported include severe leukopenia (32%), severe thrombocytopenia (27%), and severe anemia (37%).
Frequently reported nonhematologic adverse events associated with use of Hycamtin included nausea (64%), vomiting (45%), diarrhea (32%), alopecia (49%), fatigue (29%), and dyspnea (22%). Most nonhematologic toxicities were grade 1 or 2.
Adverse Events for Cervical Cancer
The most common serious adverse event is myelosuppression.
Frequently reported grade 3/4 adverse events associated with use of Hycamtin/cisplatin included neutropenia (74%), leukopenia (66%), anemia (40%), thrombocytopenia (33%), pain (22%), vomiting (15%), nausea (14%), other GI (14%), metabolic/laboratory (14%), and genitourinary (12%).
See manufacturer’s Prescribing Information for cisplatin administration and hydration guidelines, and for cisplatin dosage adjustment in the event of hematologic toxicity.
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