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Adriamycin cardiotoxicity: a survey of 1273 patients
Insights
This study investigated Adriamycin (ADR)-related cardiomyopathy (CMP) in 1273 patients. Key co-factors included total ADR dose, concurrent vincristine, prior bleomycin, and mediastinal radiotherapy, with slow infusion reducing risk.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Adriamycin (ADR) is a widely used chemotherapy agent.
- Cardiomyopathy (CMP) is a known, serious side effect of ADR treatment.
- Understanding ADR-CMP incidence and risk factors is crucial for patient safety.
Purpose of the Study:
- To determine the incidence and characteristics of Adriamycin (ADR)-related cardiomyopathy (CMP).
- To identify potential co-factors associated with ADR-induced CMP in cancer patients.
- To evaluate the impact of administration methods (infusion vs. bolus) on ADR-CMP development.
Main Methods:
- Retrospective analysis of 1273 patients from 12 European cancer centers treated with Adriamycin (ADR).
- Data collected via coded patient forms on medical history, clinical course, and chemotherapy regimens.
- Statistical analysis to identify significant associations between co-factors and ADR-CMP occurrence.
Main Results:
- "Definite" ADR-CMP occurred in 1.7% of patients, with "possible" ADR-CMP in 3%.
- Significant co-factors for "definite" ADR-CMP included total ADR dose, concurrent vincristine, prior bleomycin, and mediastinal radiotherapy.
- Slow ADR infusion was associated with a lower incidence of "definite" ADR-CMP compared to bolus injection.
Conclusions:
- Adriamycin (ADR)-related cardiomyopathy (CMP) is a significant concern, with identifiable risk factors.
- Optimizing ADR administration (e.g., slow infusion) and considering co-administered drugs and radiotherapy may mitigate CMP risk.
- Pre-existing conditions like ECG abnormalities and hypertension are associated with "possible" ADR-CMP.
Abstract:
Valuable information was collected on the medical history and clinical course of 1273 patients entered in clinical trials with Adriamycin (ADR) carried out in 12 European cancer centers. A coded patient form was used for the data collection carried out in each center by a qualified physician following a guideline which was discussed and accepted by all of the participants. The aim of the study was to define the incidence, characteristics, and possible co-factors of the cardiomyopathy (CMP) in patients treated with combination chemotherapy regimens including ADR. The mean total dose of ADR was 268 mg/m2 (range, 15--1251 mg/m2), and 5.1% of the patients received a total dose of greater than 550 mg/m2. A "definite" ADR-related CMP was observed in 1.7% of the cases; another 3% of the cases were reported as "possible" ADR-CMP since the role played by the drug could not be clearly defined. "Definite" ADR-CMP was fatal in eight patients (0.6%) while "possible" ADR-CMP was fatal in 13 patients (1.0%). Among the possible co-factors examined, the following ones were found to be significantly associated with the occurrence of a "definite" ADR-CMP: (a) total dose of ADR; (b) vincristine when given both before and concomitantly with ADR; (c) bleomycin when given before ADR; and (d) radiotherapy to the mediastinum when given concomitantly with ADR. Furthermore, none of 182 patients receiving ADR by slow infusion developed a "definite" ADR-CMP, while 2% of the patients treated by bolus injection did so. The occurrence of a "possible" ADR-CMP was found to be significantly associated with two pre-existing pathologic conditions (electrocardiogram [ECG] abnormalities and hypertension) but not with the treatment-related co-factors for the "definite" ADR-CMP mentioned above. Other variables examined, such as sex, age, cancer type, baseline liver function, and cyclophosphamide treatment, did not seem to influence the risk of ADR-CMP. Data on ECG changes occurring during ADR treatment were also reported and their incidence was found to be strictly related to the frequency of the ECG monitoring.