Radiation recall phenomenon secondary to capecitabine: possible role of thymidine phosphorylase.
BACKGROUND
The first reported case of radiation (XRT) recall related to capecitabine described dermatitis in a previously radiated field in a breast cancer patient (Ortman; JCO). We previously reported the first case of recall syndrome manifesting as diffuse gastritis and duodenitis related to capecitabine with prior XRT with 5-FU in a pancreatic cancer patient (Saif; JARCET). We report here another pancreatic cancer patient with a radiation recall receiving capecitabine following capecitabine-XRT.


METHODS
From April 2004 to June 2005, 20 patients with locally advanced pancreatic adenocarcinoma were treated with capecitabine 1,600 mg/m2 daily with concomitant radiation (5040cGy) Monday-Friday (weekends off) for a total of 6 weeks, followed by capecitabine 2,000 mg/m2 daily for 14 days every 3 weeks. One male patient with tumor in the neck and body of pancreas and not infiltrating the duodenum dropped hemoglobin to 7.3 g/dl at the end of the ninth week, and melena on rectal examination. Specimen of primary pancreatic ductal adenocarcinoma was obtained via EUS-guided biopsy before starting XRT on day 1 and utilized for RNA extraction. TP mRNA level was determined by real-time quantitative PCR (RT-Q-PCR).


RESULTS
Upper endoscopy revealed gastritis consistent with radiation toxicity. Colonoscopy was negative. Transfusion of three units of packed red blood cells (PRBCs) was given. The dose of capecitabine was reduced by 25%. His anemia continued to progress, a CT scan revealed 39% decrease in the tumor size (PR). Analysis of tumor specimen prior to the start of capecitabine-XRT showed TP expression of 183.16 (high). In addition to TP, DPD was 7.40, and TNF-alpha 4,114.56.


CONCLUSIONS
We believe this case to be the second case of radiation recall presenting as diffuse gastritis in a patient receiving capecitabine after previous treatment with XRT. Further studies, including the role of TP are warranted into the pathogenesis of this unique phenomenon.
Saif
Muhammad Wasif
MW
Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, FMP 116, New Haven, CT 06520, USA. wasif.saif@yale.edu
Black
Glenda
G
Johnson
Martin
M
Russo
Suzanne
S
Diasio
Robert
R
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005756:Gastritis / Q000139:chemically induced / Q000209:etiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011855:Radiodermatitis / Q000139:chemically induced / Q000209:etiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013939:Thymidine Phosphorylase / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003841:Deoxycytidine; D000069287:Capecitabine; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; D005472:Fluorouracil