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Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma

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Abstract

Purpose

Cisplatin-based chemotherapies are standard treatment regimens of advanced urothelial cell carcinoma. But a significant proportion of patients are unsuitable for cisplatin due to impaired renal function. Carboplatin-based regimens such as gemcitabine and carboplatin regimen (GCb) were applied due to less nephrotoxicity and side effects in these patients. However, it is known that clinical outcome of carboplatin-based regimens was unsatisfactory compared to cisplatin-based regimens. We compared the nephrotoxicity and response to treatment between GCb and gemcitabine plus split-dose cisplatin regimen (GC-S).

Methods

GC-S consists of cisplatin 35 mg/m2 given on day 1, 2 and gemcitabine 1000 mg/m2 on day 1, 8 every 3 weeks. GCb consists of carboplatin (AUC 4.5) on day 1 and gemcitabine 1000 mg/m2 on day 1, 8 every 3 weeks. Patient demographics, serum creatinine and calculated GFR, adverse events, and radiologic response were retrospectively reviewed.

Results

Forty-four patients with advanced urothelial carcinoma treated with GCb (n = 22) or GC-S (n = 22) in our institution. There was no difference at deterioration of serum creatinine or GFR between GCb and GC-S (p = 0.442, p = 0.345). For patients who had GFR < 60 mL/min/1.73 m2 subgroup, similar results were produced (p = 0.292, p = 0.186). In addition, GC-S (68.4 %) showed improved response compared to GCb (31.6 %) (p = 0.023). Both treatments were well tolerated, and there were no unexpected serious adverse events.

Conclusions

Based on preserved renal function, favorable response, and tolerability, GC-S could be a promising alternative to GCb for cisplatin-unfit patients with advanced urothelial carcinoma.

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Acknowledgments

This study was supported by a Grant (HI12C1788, HI14C1931, HI14C1731) from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

This study was reviewed and approved by the Institutional Review Board of Asan Medical Center. For this type of study, formal consent is not required.

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Authors

Corresponding author

Correspondence to Jae Lyun Lee.

Appendices

Appendix 1

See Fig. 3a, b.

Fig. 3
figure 3

Percentage changes in renal function in patients who received six cycles or more. Due to insufficient number of patients, p value could not be obtained. Error bars indicate the standard error of the mean

Appendix 2

Statistical data about changes of renal function and response to treatments (see Tables 3, 4 and 5).

Table 3 Baseline characteristics (absolute value)
Table 4 Baseline characteristics (percentile change)
Table 5 Treatment comparison

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Kim, Y.R., Lee, J.L., You, D. et al. Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma. Cancer Chemother Pharmacol 76, 141–153 (2015). https://doi.org/10.1007/s00280-015-2774-z

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