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Pharmacokinetics and safety of lobaplatin plus etoposide in Chinese men older than 65 years with extensive-stage small cell lung cancer: a phase II clinical trial

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Abstract

Purpose

This phase II, multicenter, single arm clinical study was first performed to evaluate the therapeutic efficacy and safety of the regimen—a combination of lobaplatin (LBP) and etoposide (VP-16)—and investigate the pharmacokinetics of LBP in Chinese men older than 65 years with extensive-stage small cell lung cancer (SCLC).

Methods

Patients older than 65 were treated with the combination of LBP and VP-16 for 4–6 cycles through intravenous drip. The initial dose of VP-16 was 100 mg/m2/day for d1-d3 in each 21-day cycle, while LBP was administrated for d1 in each cycle based on creatinine clearance (Ccr), 20 mg/m2 for Ccr < 60 mL/min; 25 mg/m2 for 60 ≤ Ccr < 80 mL/min and 30 mg/m2 for Ccr ≥ 80 mL/min. Efficacy, safety and pharmacokinetics were evaluated to confirm the therapeutic effect.

Results

Thirteen elderly patients were enrolled and three patients were discontinued. The median progress-free survival was 129 days and the median overall survival was 238 days, which caused a significantly prolonged survival rate of 38.5% and a higher disease control rate of 80%. Most frequent adverse events were mild to moderate containing leukopenia, neutropenia, anemia, nausea and anorexia. Pharmacokinetic analysis revealed that there is no significant difference between LP-D1 and LP-D2 at the same dosage level. With the dosage increasing, the elimination clearance showed a slowing tendency, especially for 30 mg/m2 group.

Conclusions

LBP (20, 25, 30 mg/m2) in combination with VP-16 (100 mg/m2) could inhibit the elderly SCLC disease process, prolong their survival time and reduce adverse reactions via preliminary assessment and provide guidance for further investigation.

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Acknowledgements

Authors want to thank Ph.D Zhang for support and access to biological samples.

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Author notes

  1. Jianhua Chen and Bingyang Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Mailbox 39#, 103 Wenhua Road, Shenyang, 110016, China

    Bingyang Liu, Fang Zhang, Weiping Cui & Peng Zhang

  2. Hunan Provincial Cancer Hospital, Changsha, 410013, China

    Jianhua Chen

Authors
  1. Jianhua Chen
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  2. Bingyang Liu
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  3. Fang Zhang
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  4. Weiping Cui
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  5. Peng Zhang
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Correspondence to Peng Zhang.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional. Informed consent was obtained from all individual participants included in the studies.

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Chen, J., Liu, B., Zhang, F. et al. Pharmacokinetics and safety of lobaplatin plus etoposide in Chinese men older than 65 years with extensive-stage small cell lung cancer: a phase II clinical trial. Cancer Chemother Pharmacol 84, 73–81 (2019). https://doi.org/10.1007/s00280-019-03828-z

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  • DOI: https://doi.org/10.1007/s00280-019-03828-z

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