How does idarubicin work?
Idarubicin is an anthracycline, a class of compounds that interferes with the ability of cancer cells to divide and survive.
Idarubicin works in two ways:
- It inhibits an enzyme called topoisomerase 2, which is required for DNA replication and transcription. Essentially, it prevents cancer cells from dividing and creating new cells, and from making proteins.
- It generates free oxygen radicals or reactive oxygen species (ROS), which are toxic to cancer cells and induce cell death.
Idarubicin in clinical trials
Idarubicin can be used either alone or in combination with other chemotherapy agents in myeloma patients.
A randomized Phase 3 clinical trial (NCT00006232) compared the efficacy of two combination chemotherapy regimens, Z-Dex (oral idarubicin and oral dexamethasone) and VAD (vincristine, doxorubicin, and dexamethasone; via IV injection) in previously untreated people with stage 2 or 3 multiple myeloma. The primary outcome measures were complete and partial response rates. During the trial, 106 multiple myeloma patients randomly given four to six cycles of Z‐Dex or VAD treatment.
The results of this study were reported in the British Journal of Hematology. They showed that grade 3/4 neutropenia and infections were comparable for both Z-Dex and VAD treatment groups. Complete or partial responses were found in 58% of Z-Dex-treated patients and 74% of VAD treated patients. Researchers concluded that Z-Dex is a suitable oral alternative to VAD for the treatment of newly diagnosed myeloma patients.
A randomized Phase 3 clinical trial (NCT00003603) compared the efficacy of two combination chemotherapies, CIDEX (lomustine, idarubicin, and dexamethasone) and melphalan plus prednisolone in myeloma patients who relapsed for a first time. Patients in the CIDEX arm received 25 or 50 mg/m2 of oral lomustine on day 1, 10 mg/m2 of oral idarubicin once daily on days 1 to 3, and 10 mg of oral dexamethasone twice a day on days one to four. The treatment cycle was repeated every 28 days for six to nine courses until disease progression.
Trial results were reported in the British Journal of Hematology. The overall response rate (ORR) among the 57 patients enrolled in this study was 49%, of which 30% was a partial response. ORR in patients with relapse (for unknown reasons) was 56% compared to 31% in patients with refractory (treatment resistant) disease. The major toxicity was neutropenia, but otherwise, the regimen was well tolerated. The median survival of all patients was 15 months, and 30% of patients were alive at two years after the start of the regimen. Hence, it was concluded that the CIDEX regimen was an effective treatment option available for relapsed myeloma.
A clinical study tested the efficacy of oral idarubicin as a single-agent therapy in patients with relapsed or refractory myeloma. In this study, 14 patients, previously treated with chemotherapy that included anthracyclines and unsuitable for standard therapy, were treated with 10 mg of idarubicin three times weekly for three weeks, in a five-week cycle that was repeated for a maximum of six courses.
Results of this study, reported in the Leukemia & Lymphoma journal, showed minor responses in two of its 14 patients, but no evidence of the severe toxicity associated with other anthracyclines. Its investigators concluded that oral idarubicin may be used as a single agent or in a combination therapy for patients not able to use for standard therapy.
Another clinical study tested the efficacy of oral idarubicin, vincristine and dexamethasone (VID) in multiple myeloma patients. This study enrolled 53 patients, of which 46% had primary or secondary refractory disease, 20% had been previously treated with a continuous infusion of vincristine and doxorubicin plus high-dose dexamethasone (VAD), 30% had previously untreated disease, and 4% had two or more relapses. Those enrolled were given 1.6 mg per m2 bolus injection of vincristine on day 1, 10 mg per m2 per day idarubicin capsules on days 1 to 4, and 40 mg oral dexamethasone on days 1 to 4, 9 to 12, and days 17 to 20.
Results of this study, reported in Leukemia, found that 45% of the 42 patients who completed the study achieved partial remission, and 26% a minor remission. Study investigators concluded that VID treatment was an effective and convenient alternative for VAD for multiple myeloma, including for patients with relapsed or refractory disease.
A known serious side effect of the cumulative (and dose-dependent) use of anthracyclines in both children and adults is cardiotoxicity, which can cause heart failure. Idarubicin is seen to be less toxic than other anthracyclines, including daunorubicin and doxorubicin.
Last updated: Feb. 3, 2020
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