Pediatric Hematology and Oncology, 29:549–550, 2012Copyright C© Informa Healthcare USA, Inc.ISSN: 0888-0018 print / 1521-0669 onlineDOI: 10.3109/08880018.2012.709586

SOLID TUMORS

Colon Carcinoma in a Child Treated with Oxaliplatinand Antiangiogenic Treatment Regimens

Nada Krstovski,1,2 Lidija Dokmanovic,1,2 Jelena Lazic,2 Predrag Rodic,2

Lejla Paripovic,3 and Dragana Janic1,2

1Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 2Department of Hematologyand Oncology, University Children’s Hospital, Belgrade, Serbia; 3Department of PediatricOncology, Institute of Oncology and Radiology, Belgrade, Serbia

Colorectal carcinoma is an extremely rare tumor in childhood. Therefore, the role of adjuvantchemotherapy has not been adequately evaluated in children leading to limited data on safetyprofile and treatment response after application of novel drugs and novel targeted agents. In thisreport, we describe a case of colon adenocarcinoma in a 13-year-old girl treated with standardadult treatment as well as novel targeted therapy. This case report illustrates initial good diseasecontrol with FOLFOX therapy. On the other hand, targeted therapy revealed no improvement indisease control and good safety profile without significant adverse effects.

Keywords carcinoma, childhood, colon, therapy

The role of adjuvant chemotherapy in colorectal carcinoma (CRC) in childhood hasnot been adequately evaluated leading to limited data on safety profile and treatmentresponse after application of novel drugs and novel targeted agents [1]. Here, we de-scribe a 13-year-old girl with 1 year history of anemia and intermittent abdominalpain. Physical exam showed enlarged liver, and laboratory analysis revealed slightlyelevated aminotransferases, gamma-glutamyl transpeptidase, as well as highly ele-vated carcinoembryonic antigen (CEA) at 2695 µg/L and alpha-fetoprotein (AFP) at>30,000 µg/L. Abdominal computed tomography (CT) showed multiple liver metas-tases and a conglomerate of enlarged lymph nodes in ileocecal region. Liver biopsyrevealed metastatic adenocarcinoma, with positive cytokeratine (CK) 20 and CDX 2,as well as negative CK 7, thyroid transcription factor, oestrogen, and progesteronestain. Therapy according to FOLFOX regimen (5-fluorouracil (5-FU) 600 mg/m2 ondays 1 and 2, oxaliplatin 85 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and2)[2] was administered in total of nine cycles, during 5 months. Control abdominal CTafter 1 month showed liver tumor mass reduction. After eight chemotherapy cycles,control AFP and CEA values dropped significantly. FOLFOX therapy passed withoutmajor side effects except for mild anemia, neutropenia, nausea, and paresthesias. Af-ter 4-month therapy, complete tumor resection en bloc with cecum and ileum wasperformed along with liver biopsy. Postoperative FOLFIRI therapy regimen [2] pluscetuximab (total of nine cycles every 2 weeks) was administered (irinotecan180 mg/m2 on day 1, leucovorin 400 mg/m2 on day 1, 5-FU 400 mg/m2 on day 1,

Received 1 June 2012; accepted 3 July 2012.Address correspondence to Dragana Janic, Department of Hematology and Oncology, UniversityChildren’s Hospital, Tirsova 10, 11000 Belgrade, Serbia. E-mail: dragana.janic@mfub.bg.ac.rs

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1200 mg/m2 on days 2 and 3, cetuximab 500 mg/m2). Due to disease progression,therapy consisting of bevacizumab plus capecitabine (two cycles, every 3 weeks: beva-cizumab 7.5 mg/m2 on day 1, capecitabine 1250 mg/m2 days 1–14) followed by 5-FUplus bevacizumab (every 2 weeks during 4 months, leucovorin 400 mg/m2 on day 1,5-FU 400 mg/m2 on day 1, then 1200 mg/m2 on days 2 and 3, bevacizumab 5 mg/m2)during 4 months was tried but without success. Except for paronychia, no other ad-verse effects of this therapy were detected. Lethal outcome of the disease occurred 21months after diagnosis.

Optimal therapy for metastatic CRC in children is unknown. The role of adjuvantchemotherapy has not been adequately evaluated in children but most patients re-ceive standard 5-FU/leucovorin combination [1]. The addition of oxaliplatin improvesrelapse-free survival in adults, but large case series are lacking on the effects of thisdrug in children. Our patient received nine chemotherapy cycles with oxaliplatin, intotal, without significant adverse effects, except for mild myelosupression, nausea,and paresthesias. The initial good disease control in our patient may probably be, atleast partly, explained by oxaliplatin addition to 5-FU/leucovorin regimen. In adults,discontinuation of oxaliplatin due to toxicity should be strongly considered after 3–4months of therapy with other drugs maintained until tumor progression. While stan-dard 5-FU/leucovorin regimen has often been used as adjuvant therapy for CRC inchildren, oxaliplatin and novel targeted therapies have been rarely reported treatmentmodalities. For this reason, safety profile of these drugs and treatment response inchildren are unknown. Our patient experienced no serious side effects previously de-scribed in the literature such as diarrhea, rash, hypertension, or ocular toxicity [3–5].Although safety of oxaliplatin and targeted therapies such as cetuximab and beva-cizumab cannot be shown based on one patient report, we believe that our experi-ence can contribute to total knowledge of application of these drugs in children withthis rare form of malignancy.

Declaration of Interest

This work is supported by grant number III 41004, Ministry of Education and Science,Republic of Serbia. The authors report no conflicts of interest. The authors alone areresponsible for the content and writing of the paper.

REFERENCES

[1] Saab R, Furman WL. Epidemiology and management options for colorectal cancer in children.Paediatr Drugs. 2008;10(3):177–192.

[2] National Comprehensive Cancer Network. Colon Cancer: NCCN Clinical Practice Guidelines in On-cology. Fort Washington, PA: National Comprehensive Cancer Network; 2009. http://www.nccn.org/professionals/physician gls/pdf/colon.pdf. Accessed 15 June 2009.

[3] Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352(5):476–487.[4] Rothenberg ML, Cox JV, Butts C, et al. Capecitabine plus oxaliplatin (XELOX) versus 5-

fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectalcancer: a randomized phase III noninferiority study. Ann Oncol. 2008;19(10):1720–1726.

[5] Widakowich C, de Castro G, Jr, de Azambuja E, Dinh P, Awada A. Review: side effects of approvedmolecular targeted therapies in solid cancers. Oncologist. 2007;12(12):1443–1455.

Pediatric Hematology and Oncology

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