Hycamtin vs Doxil®
(doxorubicin HCl liposome injection):
A comparative look at single-agent therapies
Gordon et al discusses a phase III, randomized, multicenter, open-label comparative study to compare the efficacy and safety of Hycamtin and Doxil in patients with epithelial ovarian carcinoma that recurred after or didn’t respond to first-line, platinum-based chemotherapy. [6]
Progression-free survival in platinum-sensitive and platinum-resistant/refractory was 17.0 weeks for Hycamtin and 16.1 weeks for Doxil (see chart below) [6]
Analysis of platinum-sensitive patients
In the subset analysis of platinum-sensitive patients, response rates were similar between Hycamtin and Doxil, but overall survival was statistically significant in favor of Doxil [6]. However, there are a few factors to highlight in regards to this conclusion:
- Definitive conclusions about overall survival cannot be drawn from this study because the absence of crossover and poststudy therapy data confound interpretation of overall survival data
- Therapy received after crossover can influence final survival results
- The likelihood that crossover therapy confounded study results was reflected by the authors’ qualifying statement in their discussion of the results:
“The significant survival advantage reported for the pegylated liposomal doxorubicin patients with platinum-sensitive disease merits further investigation. One possible explanation may be due to other therapies patients received after being removed from the study. Patients who initially received topotecan may not have subsequently received pegylated liposomal doxorubicin because it had not yet been approved for use in epithelial ovarian cancer. Unfortunately, subsequent therapy was not collected retrospectively, and it is unknown as to what therapies were administered after the failure of initial therapy.” [6]
Treatment Response for the Intent-to-Treat Population [6]
Analysis of platinum-resistant/refractory patients
Subset analysis of platinum-resistant/refractory patients treated with Hycamtin or Doxil showed similar outcomes in the 2 primary efficacy endpoints of progression-free survival and overall survival. Median progression-free survival in platinum-resistant/refractory patients was 13.6 weeks for Hycamtin and 9.1 weeks for Doxil.
Treatment Response for the Intent-to-Treat Population[6]
Adverse Events for the Intent-to-Treat Population [6]
Important Safety Information
Indications
Hycamtin is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.
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.
Adverse Events
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.
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