Treatment of a patient with advanced esophageal cancer with a combination of mitomycin C and capecitabine: activation of the thymidine phosphorylase as active principle?
BACKGROUND
Both capecitabine, an oral prodrug of 5-fluorouracil (5-FU), and mitomycin C (MMC) have demonstrated activity as single agents in patients with gastrointestinal cancer. Furthermore, a combination of MMC with infusional 5-FU can induce tumor remission even in patients pretreated with 5-FU. Capecitabine and MMC act synergistically due to an upregulation of the thymidine phosphorylase activity by MMC in a human xenograft model.


METHODS
We sought to exploit these preclinically observed effects in a patient with esophageal cancer who was progressive after a first-line radiochemotherapy with 5-FU and cisplatin. He was treated with a combination of MMC and capecitabine on a compassionate use basis. A rapid remission lasting for about 6 months was observed.


CONCLUSIONS
This is the first report on a combination therapy with capecitabine and MMC. The remission observed in our patient suggests that the preclinically observed synergy has clinical impact. This combination should be further investigated in prospective clinical trials.
Hofheinz
R-D
RD
Onkologisches Zentrum, III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Germany. ralf.hofheinz@med3.ma.uni-heidelberg.de
Weisser
A
A
Willer
A
A
Hehlmann
R
R
Hochhaus
A
A
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage* / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D013939:Thymidine Phosphorylase / Q000097:blood*; D016896:Treatment Outcome
D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil