High cumulative doxorubicin dose for advanced soft tissue sarcoma

Abstract

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.

Comparison between trabectedin and doxorubicin in soft-tissue sarcomas: a systematic review and meta-analysis

“…Table 1 provides a comprehensive description of each trial included in the meta-analysis. All the 10 articles were RCTs (19)(20)(21)(22)(23)(24)(25)(26)(27)(28). The 10 articles were published between 2015 and 2021.…”

Apatinib with doxorubicin and ifosfamide as neoadjuvant therapy for high-risk soft tissue sarcomas: a retrospective cohort study

“…The first-line treatment for advanced (locally unresectable or metastatic) STS is chemotherapy with doxorubicin [3]. The overall response rate (ORR) to this treatment for advanced STS is approximately 20% [5], and the 5-year survival rate among patients with advanced STS treated with a combination regimen is < 10% [6]. These findings suggest the need for an approach that may help reduce the rates of recurrence and metastasis in patients with early-and mid-stage STS.…”

Undifferentiated Pleomorphic Sarcoma with Neoplastic Fever: A Retrospective Study

“…10 Systemic treatment of advanced UPS includes chemotherapy, targeted therapy, and immunotherapy. 7,11 The median overall survival for latestage UPS is approximately 1 year. 6,11 Although the annual incidence of UPS is extremely low, it can be subdivided into different subtypes.…”

“…7,11 The median overall survival for latestage UPS is approximately 1 year. 6,11 Although the annual incidence of UPS is extremely low, it can be subdivided into different subtypes. 12 UPS with fever of unknown origin (also known as neoplastic fever) is a specific subtype of UPS.…”

“… 10 Systemic treatment of advanced UPS includes chemotherapy, targeted therapy, and immunotherapy. 7 , 11 The median overall survival for late-stage UPS is approximately 1 year. 6 , 11 …”