Hycamtin/cisplatin: The first and only FDA-approved regimen with a survival advantage vs cisplatin alone in patients with 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 [31]
Randomized phase III trial of cisplatin with or without Hycamtin in carcinoma of the uterine cervix: a Gynecologic Oncology Group study
Study Design
- Primary endpoint: survival
- Intent-to-treat analysis
- All regimens were to be administered for a maximum of 6 cycles for nonresponders, or until disease progression or unacceptable toxicity
- Patients with partial response and acceptable level of toxicity were permitted to continue treatment beyond 6 cycles
The study found that Hycamtin, in combination with cisplatin, was effective in treating cervical cancers which were not amenable to curative treatment with surgery and/or radiation therapy. [31]
The median survival for Hycamtin/cisplatin was 9.4 months; for cisplatin, 6.5 months.
- Overall survival significantly favored the combination
| – | Log rank P value = 0.033 (significance level was 0.044 after adjusting for the interim analysis) |
| – | The unadjusted hazard ratio was 0.76 (95% CI, 0.59-0.98) |
GOG 179: The first randomized, prospective phase III trial to demonstrate a significant survival advantage for combination chemotherapy in cervical cancer.[31]
The combination of Hycamtin/cisplatin was active in patients with cervical cancer, whether or not they had received prior cisplatin therapy [31]
- Median survival for Hycamtin/cisplatin was 9.4 months; for cisplatin, 6.5 months [31]
- Overall survival favored the combination (log rank P=0.033) [1]
- Hycamtin/cisplatin was active in patients with cervical cancer regardless of prior cisplatin-based chemoradiotherapy [31]
The Hycamtin plus cisplatin combination was generally well tolerated. The most common dose-limiting toxicity was myelosuppression. Major hematologic adverse events (grades 3 and 4) were more frequent in the combination arm than in the single-agent arm and included neutropenia (74% vs 2%), thrombocytopenia (33% vs 3%), and infection-febrile neutropenia (19% vs 8%), respectively. The most common nonhematologic adverse events reported were constitutional,* gastrointestinal, pain, and metabolic toxicities.
*Includes fatigue (lethargy, malaise, a feeling of weakness), fever (in the absence of neutropenia), rigors, chills, sweating, and weight gain or loss.
Important Safety Information
Indications
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).
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.
Dosing
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
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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