Early relapse on adjuvant gemcitabine associated with an exceptional response to 2nd line capecitabine chemotherapy in a patient with pancreatic adenosquamous carcinoma with strong intra-tumoural expression of cytidine deaminase: a case report

被引:6
作者
Connell, Claire M. [1 ,2 ]
Brais, Rebecca [1 ]
Whitaker, Hayley [3 ]
Upponi, Sara [1 ]
Beh, Ian [1 ]
Risdall, Jane [1 ]
Corrie, Pippa [1 ]
Janowitz, Tobias [1 ,2 ]
Jodrell, Duncan I. [1 ,2 ]
机构
[1] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge CB2 0QQ, England
[2] Univ Cambridge, Li Ka Shing Ctr, CRUK Cambridge Inst, Dept Oncol, Cambridge CB2 0RE, England
[3] UCL, Div Surg & Intervent Sci, Res Dept Tissue & Energy, Charles Bell House,43-45 Foley St, London W1W 7TS, England
关键词
Cytidine deaminase; Drug metabolism; Gemcitabine; Pancreatic adenosquamous carcinoma; CANCER-PATIENTS; TOXICITIES; RESECTION;
D O I
10.1186/s12885-020-6516-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Pancreatic adenosquamous carcinoma has a poor prognosis, with limited prospective trial data to guide optimal treatment. The potential impact of drug metabolism on the treatment response of patients with pancreatic adenosquamous carcinoma is largely unknown. Case presentation We describe the case of a 51 year old woman with pancreatic adenosquamous carcinoma who, following surgical resection, experienced early disease relapse during adjuvant gemcitabine therapy. Paradoxically, this was followed by an exceptional response to capecitabine therapy lasting 34.6 months. Strong expression of cytidine deaminase was detected within the tumour. Conclusions This case study demonstrates that early relapse during adjuvant chemotherapy for pancreatic adenosquamous carcinoma may be compatible with a subsequent exceptional response to second line chemotherapy, an important observation given the poor overall prognosis of patients with adenosquamous carcinoma. Cytidine deaminase is predicted to inactivate gemcitabine and, conversely, catalyze capecitabine activation. We discuss strong intra-tumoural expression of cytidine deaminase as a potential mechanism to explain this patient's disparate responses to gemcitabine and capecitabine therapy, and highlight the benefit that may be gained from considering similar determinants of response to chemotherapy in clinical practice.
引用
收藏
页数:6
相关论文
共 24 条
[1]   A PHASE-I CLINICAL, PLASMA, AND CELLULAR PHARMACOLOGY STUDY OF GEMCITABINE [J].
ABBRUZZESE, JL ;
GRUNEWALD, R ;
WEEKS, EA ;
GRAVEL, D ;
ADAMS, T ;
NOWAK, B ;
MINEISHI, S ;
TARASSOFF, P ;
SATTERLEE, W ;
RABER, MN ;
PLUNKETT, W .
JOURNAL OF CLINICAL ONCOLOGY, 1991, 9 (03) :491-498
[2]   Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma [J].
Bengala, C ;
Guarneri, V ;
Giovannetti, E ;
Lencioni, M ;
Fontana, E ;
Mey, V ;
Fontana, A ;
Boggi, U ;
Del Chiaro, M ;
Danesi, R ;
Ricci, S ;
Mosca, F ;
Del Tacca, M ;
Conte, PF .
BRITISH JOURNAL OF CANCER, 2005, 93 (01) :35-40
[3]   Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review [J].
Borazanci, Erkut ;
Millis, Sherri Z. ;
Korn, Ron ;
Han, Haiyong ;
Whatcott, Clifford J. ;
Gatalica, Zoran ;
Barrett, Michael T. ;
Cridebring, Derek ;
Von Hoff, Daniel D. .
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY, 2015, 7 (09) :132-140
[4]  
CORRIE P, 2017, ANN ONCOL, V28, p73P, DOI DOI 10.1093/annonc/mdx369.121
[5]   Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-upaEuro [J].
Ducreux, M. ;
Cuhna, A. Sa. ;
Caramella, C. ;
Hollebecque, A. ;
Burtin, P. ;
Goere, D. ;
Seufferlein, T. ;
Haustermans, K. ;
Van Laethem, J. L. ;
Conroy, T. ;
Arnold, D. .
ANNALS OF ONCOLOGY, 2015, 26 :V56-V68
[6]   nab-Paclitaxel Potentiates Gemcitabine Activity by Reducing Cytidine Deaminase Levels in a Mouse Model of Pancreatic Cancer [J].
Frese, Kristopher K. ;
Neesse, Albrecht ;
Cook, Natalie ;
Bapiro, Tashinga E. ;
Lolkema, Martijn P. ;
Jodrell, Duncan I. ;
Tuveson, David A. .
CANCER DISCOVERY, 2012, 2 (03) :260-269
[7]   Adenosquamous Versus Adenocarcinoma of the Pancreas: A Population-Based Outcomes Analysis [J].
Katz, Matthew Harold G. ;
Taylor, Thomas H. ;
Al-Refaie, Waddah B. ;
Hanna, Mark H. ;
Imagawa, David K. ;
Anton-Culver, Hoda ;
Zell, Jason A. .
JOURNAL OF GASTROINTESTINAL SURGERY, 2011, 15 (01) :165-174
[8]   Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline [J].
Khorana, Alok A. ;
Mangu, Pamela B. ;
Berlin, Jordan ;
Engebretson, Anitra ;
Hong, Theodore S. ;
Maitra, Anirban ;
Mohile, Supriya G. ;
Mumber, Matthew ;
Schulick, Richard ;
Shapiro, Marc ;
Urba, Susan ;
Zeh, Herbert J. ;
Katz, Matthew H. G. .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (21) :2541-+
[9]  
De Souza AL, 2014, J PANCREAS, V15, P144, DOI 10.6092/1590-8577/2358
[10]   Genotype-based methods for anticipating gemcitabine-related severe toxicities may lead to false-negative results [J].
Mercier, Cedric ;
Evrard, Alexandre ;
Ciccolini, Joseph .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (30) :4855-4855