1608P - Chemotherapy for dihydropyrimidine dehydrogenase-deficient patient

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Complications of Treatment
Cancer in Special Situations
Presenter Youichirou Yoshida
Citation Annals of Oncology (2014) 25 (suppl_4): iv546-iv563. 10.1093/annonc/mdu358
Authors Y. Yoshida1, N. Aisu1, S. Tanimura1, S. Hoshino1, K. Ogata2, M. Uchiyama3, S. Hara2, A. Mogi4, Y. Takamatsu4, K. Hirata5, K. Tamura4, H. Mishima6, Y. Yamashita1
  • 1Gastroenterological Surgery, Fukuoka University Faculty of Medicine, 8140180 - Fukuoka/JP
  • 2Faculty Of Pharmaceutical Sciences, Fukuoka University, 814-0180 - Fukuoka/JP
  • 3Pharmacy, Fukuoka University Hospital, 814-0180 - Fukuoka/JP
  • 4Division Of Medical Oncology, Hematology And Infectious Disease, Fukuoka University Facultyl of Medicine, 814-0180 - Fukuoka/JP
  • 5Surgery, Fukuoka Sanno Hospital, 8140001 - Fukuoka/JP
  • 6Clinical Oncology, Aichi Medical University, 480-1195 - Nagakute/JP

Abstract

Aim

5-FU is metabolized by thymidine phosphorylase and orotate phosphoribosyl transferase and is principally degraded in the blood or liver by dihydropyrimidine dehydrogenase (DPD). DPD, the catalyzing enzyme in the first and rate-limiting step of the degradation process, degrades approximately 85% of the administered 5-FU. DPD activity in peripheral blood mononuclear cells has been reported to correlate inversely with 5-FU clearance. In reports of DPD deficiency, the prognosis is poor, and approximately 60% patients die. With a reported high mortality rate, chemotherapy is generally contraindicated for patients with DPD deficiency, and there have been no reports of continued chemotherapy in patients with a DPD activity level of <10%. Here we report the new findings of DPD-deficient patient in whom continuing chemotherapy through the dose-escalation method is successful.

Methods

Chemotherapy for a 73-year old man with jejunal cancer was initiated. Capecitabine was administered in incrementally increasing doses, beginning with a single pill (dose-escalation method), while monitoring plasma 5-FU concentration, leukocyte, neutrophil, and platelet counts.

Results

DPD protein measurement in the peripheral blood mononuclear cells yielded a level of 2.35 U/mg using the ELISA method (the same method yielded DPD measurements ranging from 33.6 to 183.6 U/mg in peripheral blood mononuclear cells from 10 healthy individuals). Ultimately, after increasing the Capecitabine dose to 1800 mg, oxaliplatin and bevacizumab were added and XELOX+bevacizumab treatment was initiated. Subsequent DPD protein measurement showed that the level had increased to approximately 10-fold the level before chemotherapy. Furthermore, the peritoneal metastases disappeared following chemotherapy.

Conclusions

Because of serious adverse events, the chemotherapy-associated mortality rate among DPD-deficient patients is high, and there have been no reports of continuous chemotherapy in patients with DPD activity levels of <10%. This report is the first of its kind worldwide and has indicated that DPD activity can be inducible. These findings may provide early indications of a new treatment method for DPD deficiency and will be reported in detail.

Disclosure

All authors have declared no conflicts of interest.