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Phase I study of pegylated liposomal doxorubicin and cisplatin in patients with advanced osteosarcoma

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Abstract

Purpose

The repeated use of doxorubicin is limited due to dose-limiting cardiac toxicity. Pegylated liposomal doxorubicin (PEG-LD, Duomeisu) has a reduced cardiac toxicity. This phase I study aimed to investigate the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the PEG-LD and cisplatin combination in patients with metastatic and recurrent osteosarcoma.

Methods

Patients were given PEG-LD at a dose of 40, 50, or 60 mg/m2 on day 1 of each 21-day cycle, according to a 3 + 3 approach for dose escalation. Cisplatin was administered as a fixed dose of 100 mg/m2 for every cycle. Toxicities and tumor response were observed.

Results

A total of 15 patients were enrolled in this trial, and nine of the patients had received prior doxorubicin. The MTD of PEG-LD was reached at 50 mg/m2 in this regimen, with neutropenic fever and stomatitis as DTLs. The main adverse event (AE) was myelosuppression. The most common non-hematological AEs were vomiting, hypoproteinemia, stomatitis and transient sinus arrhythmia. Grade 3–4 toxicity was neutropenia, leukopenia, thrombocytopenia, anemia and stomatitis in the whole cohort. All the AEs were relieved after symptomatic and supportive treatment. Totally, the overall response rate was 13.3% and disease control rate was 66.7%. For the six patients who have not received prior doxorubicin, one partial response and five stable diseases were observed.

Conclusion

We provide the data showing that PEG-LD 50 mg/m2 combined with cisplatin 100 mg/m2 demonstrated an acceptable safety profile and promising clinical activity in advanced osteosarcoma, which merits further evaluation in phase II studies.

Trial registration

ChiCTR1900021550.

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Availability of data and material

Data supporting the results reported in this study are not publicly available but are accessible from the corresponding author on reasonable request.

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Acknowledgements

We are grateful to our patients and their families for participating in this study.

Funding

Not applicable.

Author information

Author notes

  1. Xi-zhi Wen and Qiu-zhong Pan contributed equally to this work.

Authors and Affiliations

  1. Melanoma and Sarcoma Medical Oncology Unit, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, People’s Republic of China

    Xi-zhi Wen, Qiu-zhong Pan, Bu-shu Xu, De-sheng Weng, Jing-jing Zhao & Xing Zhang

  2. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China

    Xi-zhi Wen, Qiu-zhong Pan, Bu-shu Xu, Wei Xiao, De-sheng Weng, Jing-jing Zhao & Xing Zhang

  3. Department of Hematological Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, People’s Republic of China

    Wei Xiao

  4. Department of Orthopaedic Oncology Surgery, Beijing Jishuitan Hospital, Beijing, 100000, China

    Hai-rong Xu, Zhen Huang & Xiao-hui Niu

Authors
  1. Xi-zhi Wen
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Contributions

XZW, XHN and XZ designed the study. XZW, QZP, BSX, WX, DSW, JJZ, HRX, ZH and XZ conducted the study and collected the data. XZW, QZP, XHN and XZ analyzed the data and interpreted the results. XZW, QZP, XHN and XZ wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiao-hui Niu or Xing Zhang.

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Conflict of interest

The authors declare that they have no completing interests.

Ethical approval

The study was approved by the Scientific and Ethics Committees of Sun Yat-sen University Cancer Center (Number B2018-102-05).

Consent to participate

Each patient signed a written informed consent before participating to this study (Trial Registration: ChiCTR, ChiCTR1900021550).

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Wen, Xz., Pan, Qz., Xu, Bs. et al. Phase I study of pegylated liposomal doxorubicin and cisplatin in patients with advanced osteosarcoma. Cancer Chemother Pharmacol 89, 209–215 (2022). https://doi.org/10.1007/s00280-021-04371-6

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  • DOI: https://doi.org/10.1007/s00280-021-04371-6

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