Skip to main content

Advertisement

Log in

The risk factors for oxaliplatin-induced peripheral sensory neuropathy and thrombocytopenia in advanced gastric cancer

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Peripheral sensory neuropathy (PSN) and thrombocytopenia are the main dose-limiting toxicities of oxaliplatin for the treatment of advanced gastric cancer (AGC). Because the risk factors for those toxicities in practice have not been clarified, we conducted this prospective study.

Methods

AGC patients who received oxaliplatin-based therapy at any of seven institutions participating in the Kyushu Medical Oncology Group were assessed after we obtained written informed consent.

Results

A total of 60 patients including 39 males and 21 females were examined. The median age was 66 years. The numbers of patients receiving oxaliplatin as the first, second, or third and later lines of therapy were 39, 16, and 5, respectively. An initial dose of 130, 100, or < 100 mg/m2 oxaliplatin was administered to 12, 39, and 9 patients, respectively. S-1 or capecitabine as a concomitant drug was administered in 54 and 6 patients, respectively. In multivariate analysis, the comorbidity of diabetes mellitus was associated with ≥ grade 2 thrombocytopenia (p = 0.035). No significant risk factor was associated with ≥ grade 2 PSN. However, the accumulated dose of oxaliplatin exhibited a strong correlation with ≥ grade 2 PSN (p = 0.0043), and the predicted accumulated dose of oxaliplatin in which 10% of patients developed ≥ grade 2 PSN was 800 mg/m2. The frequency of PSN in subsequent paclitaxel therapy in patients with ≥ grade 2 or worse PSN in oxaliplatin-based chemotherapy did not increase compared to those with none or grade 1 PSN in oxaliplatin.

Conclusion

Thrombocytopenia in AGC patients with diabetes mellitus should be carefully monitored during oxaliplatin-based therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ferlay J, Bray F, Parkin DM, Pisani P (eds) (2001) Globocan 2000: cancer incidence and mortality worldwide (IARC Cancer Base No. 5). IARC Press, Lyon

    Google Scholar 

  2. Cunningham D, Starling N, Rao S et al (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358:36–46. https://doi.org/10.1056/NEJMoa073149

    Article  PubMed  CAS  Google Scholar 

  3. Bang YJ, Van Cutsem E, Feyereislova A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376:687–697. https://doi.org/10.1016/S0140-6736(10)61121-X

    Article  PubMed  CAS  Google Scholar 

  4. Van Cutsem E, Moiseyenko VM, Tjulandin S et al (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first line therapy for advanced gastric cancer: a report of the V325 study group. J Clin Oncol 24:4991–4997

    Article  PubMed  CAS  Google Scholar 

  5. Koizumi W, Narahara H, Hara T et al (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221. https://doi.org/10.1016/S1470-2045(08)70035-4

    Article  PubMed  CAS  Google Scholar 

  6. Kang YK, Kang WK, Shin DB et al (2009) Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 20:666–673. https://doi.org/10.1093/annonc/mdn717

    Article  PubMed  Google Scholar 

  7. Al-Batran SE, Hartmann JT, Probst S et al (2008) Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 26:1435–1442. https://doi.org/10.1200/JCO.2007.13.9378

    Article  PubMed  CAS  Google Scholar 

  8. Hironaka S, Ueda S, Yasui H et al (2013) Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol 31:4438–4444. https://doi.org/10.1200/JCO.2012.48.5805

    Article  PubMed  CAS  Google Scholar 

  9. Saltz LB, Clarke S, Díaz-Rubio E et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019. https://doi.org/10.1200/JCO.2007.14.9930

    Article  PubMed  CAS  Google Scholar 

  10. Yamada Y, Higuchi K, Nishikawa K et al (2015) Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol 26:141–148. https://doi.org/10.1093/annonc/mdu472

    Article  PubMed  CAS  Google Scholar 

  11. Inadomi K, Kusaba H, Matsushita Y et al (2017) Efficacy and safety analysis of oxaliplatin-based chemotherapy for advanced gastric cancer. Anticancer Res 37:2663–2671

    Article  PubMed  Google Scholar 

  12. Koizumi W, Takiuchi H, Yamada Y et al (2010) Phase II study of oxaliplatin plus S-1 as first-line treatment for advanced gastric cancer (G-SOX study). Ann Oncol 21:1001–1005. https://doi.org/10.1093/annonc/mdp464

    Article  PubMed  CAS  Google Scholar 

  13. de Gramont A, Figer A, Seymour M et al (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947

    Article  PubMed  Google Scholar 

  14. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  PubMed  CAS  Google Scholar 

  15. Cancer Therapy Evaluation Program, National Cancer Institute (2010) Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  16. Oki E, Emi Y, Kojima H et al (2015) Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study. Int J Clin Oncol 20:767–775

    Article  PubMed  CAS  Google Scholar 

  17. Loprinzi CL, Qin R, Dakhil SR et al (2014) Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol 32:997–1005

    Article  PubMed  CAS  Google Scholar 

  18. Miltenburg NC, Boogerd W (2014) Chemotherapy-induced neuropathy: a comprehensive survey. Cancer Treat Rev 40:872–882

    Article  PubMed  CAS  Google Scholar 

  19. Quasthoff S, Hartung HP (2002) Chemotherapy-induced peripheral neuropathy. J Neurol 249:9–17

    Article  PubMed  CAS  Google Scholar 

  20. Ramanathan RK, Rothenberg ML, de Gramont A et al (2010) Incidence and evolution of oxaliplatin-induced peripheral sensory neuropathy in diabetic patients with colorectal cancer: a pooled analysis of three phase III studies. Ann Oncol 21:754–758. https://doi.org/10.1093/annonc/mdp509

    Article  PubMed  CAS  Google Scholar 

  21. Jardim DL, Rodrigues CA, Novis YA, Rocha VG, Hoff PM (2012) Oxaliplatin-related thrombocytopenia. Ann Oncol 23:1937–1942. https://doi.org/10.1093/annonc/mds074

    Article  PubMed  CAS  Google Scholar 

  22. Han NY, Park BJ, Kim MJ, Sung DJ, Cho SB (2015) Hepatic parenchymal heterogeneity on contrast enhanced CT scans following oxaliplatin-based chemotherapy: natural history and association with clinical evidence of sinusoidal obstruction syndrome. Radiology 276:766–774. https://doi.org/10.1148/radiol.2015141749

    Article  PubMed  Google Scholar 

  23. Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL (2001) Platelet dysfunction in type 2 diabetes. Diabetes Care 24:1476–1485

    Article  PubMed  CAS  Google Scholar 

  24. Wilke H, Muro K, Van Cutsem E et al (2014) Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15:1224–1235. https://doi.org/10.1016/S1470-2045(14)70420-6

    Article  PubMed  CAS  Google Scholar 

  25. Cavaletti G, Cavalletti E, Oggioni N et al (2000) Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. Neurotoxicology 21:389–393

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the medical staff of each institution who contributed to treatment of the patients.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eishi Baba.

Ethics declarations

Conflict of interest

Koichi Akashi and Eishi Baba have received research grants from Yakult Honsha, Eli Lilly, Taiho Pharm, Chugai Pharm, and Nippon Kayaku. Taito Esaki received research grants from mentioned above other than Chugai Pharm. Koichi Akashi has received a speaker honorarium from Chugai Pharm. Eishi Baba has received a speaker honorarium from Chugai Pharm and Eli Lilly. Akitaka Makiyama and Taito Esaki received a speaker honorarium from Yakult Honsha, Eli Lilly, Taiho Pharm, Chugai Pharm, and Nippon Kayaku.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamaguchi, K., Kusaba, H., Makiyama, A. et al. The risk factors for oxaliplatin-induced peripheral sensory neuropathy and thrombocytopenia in advanced gastric cancer. Cancer Chemother Pharmacol 82, 625–633 (2018). https://doi.org/10.1007/s00280-018-3652-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-018-3652-2

Keywords

Navigation