High cumulative doses of doxorubicin (average 714.38 mg/m2) in patients with advanced soft tissue sarcoma resulted in a 4.17% incidence of cardiotoxicity, compared to 3.42% in the standard-dose group, suggesting it may be a viable therapeutic option.
Cohort (n=170)
No
Does a high cumulative doxorubicin dose improve efficacy without increasing cardiotoxicity in patients with advanced soft tissue sarcoma?
Continuation or rechallenge with doxorubicin beyond the recommended cumulative dose in advanced soft tissue sarcoma may offer therapeutic benefits without significantly increasing the risk of symptomatic heart failure.
Absolute Event Rate: 4.17% vs 3.42%
BACKGROUND: The recommended cumulative doxorubicin dose in soft tissue sarcoma (STS) treatment was based on cardiotoxicity data from retrospective studies of breast cancer patients. However, the treatment and prognosis of STS and breast cancer are quite different, and reference to breast cancer data alone may not reflect the efficacy of doxorubicin treatment in STS. This study, thus, aimed to review and analyze clinical data of STS patients treated with a high cumulative doxorubicin dose, to provide a reference for treatment selection and clinical trial design. METHODS: We retrospectively collected and analyzed clinical data of patients with advanced STS who received doxorubicin-based chemotherapy from January 2016 to January 2020. The patients were divided into a standard-dose group (who received ≤6 cycles of doxorubicin after the initial diagnosis) and an over-dose group (who were re-administered doxorubicin doxorubicin-rechallenge after receiving 6 cycles of doxorubicin therapy discontinuously). Patient characteristics, cumulative doxorubicin dose, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), cardiotoxicity incidence, and treatment effectiveness were evaluated in both groups. RESULTS: A total of 170 patients with advanced STS were recruited (146 in the standard-dose group and 24 in the over-dose group). The average cumulative doxorubicin dose was 364.04 ± 63.81 mg/m2 in the standard-dose group and 714.38 ± 210.09 mg/m2 in the over-dose group. The ORR, DCR, and median PFS were 15.07, 58.9%, and 6 (95% confidence interval CI: 5.8-6.5) months in the standard-dose group and 16.67, 66.67%, and 4 (95%CI: 2.0-5.8) months in the over-dose group, respectively. Symptomatic heart failure occurred in five patients (3.42%) of the standard-dose group and in one patient (4.17%) of the over-dose group. In these patients with cardiotoxicity, doxorubicin was discontinued, and all of them died of uncontrolled tumor growth. No drug-related deaths occurred. CONCLUSIONS: The continuation of or rechallenge with doxorubicin beyond the recommended cumulative dose could be a promising therapeutic option in the treatment of chemotherapy-sensitive advanced sarcomas. Further evaluation is necessary in prospective trials.
Tian et al. (Mon,) conducted a cohort in Advanced soft tissue sarcoma (n=170). High cumulative doxorubicin dose (>6 cycles) vs. Standard cumulative doxorubicin dose (≤6 cycles, average 364.04 mg/m2) was evaluated on Incidence of cardiotoxicity (symptomatic heart failure). High cumulative doses of doxorubicin (average 714.38 mg/m2) in patients with advanced soft tissue sarcoma resulted in a 4.17% incidence of cardiotoxicity, compared to 3.42% in the standard-dose group, suggesting it may be a viable therapeutic option.
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