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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 7  |  Issue : 4  |  Page : 167-169

Successful treatment with continuous high-dose 5-fluorouracil infusion, followed by oral capecitabine in a patient with advanced gastric cancer with bone marrow metastasis and microangiopathic hemolytic anemia


Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

Date of Submission07-May-2020
Date of Decision17-Aug-2020
Date of Acceptance18-Aug-2020
Date of Web Publication1-Dec-2020

Correspondence Address:
Dr. Su- Peng Yeh
Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 40447
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCRP.JCRP_20_20

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  Abstract 


A 61-year-old male with a history of Stage 1A gastric body adenocarcinoma and s/p radical subtotal gastrectomy + B-II reconstruction 5 years previously presented with general malaise and bone pain. A hemogram revealed severe anemia and thrombocytopenia, which were refractory to blood transfusion. A peripheral blood smear showed marked thrombocytopenia with numerous fragmented red blood cells and normoblasts. A bone marrow biopsy showed metastatic adenocarcinoma of gastric origin. Therefore, he was diagnosed with cancer-associated microangiopathic hemolytic anemia (MAHA). In addition to aggressive transfusion support, high-dose continuous 5-fluorouracil infusion was administered, and the MAHA and thrombocytopenia dramatically resolved. Capecitabine was subsequently administered orally at the outpatient clinic, and his disease was well controlled without the recurrence of MAHA or thrombocytopenia for 1 year. Although most chemotherapies may aggravate cytopenia, our case illustrates that effective chemotherapy can not only control cancer-associated MAHA but also restore cytopenia to normal.

Keywords: 5-fluorouracil, advanced gastric cancer, capecitabine, microangiopathic hemolytic anemia


How to cite this article:
Wang HT, Yeh SP. Successful treatment with continuous high-dose 5-fluorouracil infusion, followed by oral capecitabine in a patient with advanced gastric cancer with bone marrow metastasis and microangiopathic hemolytic anemia. J Cancer Res Pract 2020;7:167-9

How to cite this URL:
Wang HT, Yeh SP. Successful treatment with continuous high-dose 5-fluorouracil infusion, followed by oral capecitabine in a patient with advanced gastric cancer with bone marrow metastasis and microangiopathic hemolytic anemia. J Cancer Res Pract [serial online] 2020 [cited 2021 Jun 19];7:167-9. Available from: https://www.ejcrp.org/text.asp?2020/7/4/167/301907




  Introduction Top


Few patients with both gastric cancer and microangiopathic hemolytic anemia (MAHA) have been reported, and their prognosis is extremely poor, with a survival time of usually <1 month despite aggressive supportive care.[1] Treatment of cancer-associated MAHA is very difficult. Although chemotherapy with 5-fluorouracil (5-FU) and cisplatin has been widely used in patients with advanced gastric cancer with a response rate of 35%–50%,[2],[3] the use of such chemotherapy in patients with MAHA may further aggravate cytopenia due to bone marrow toxicity and increase the risk of life-threatening hemorrhage. Infusion of 5-FU is an effective regimen for advanced gastric cancer with negligible myelosuppression; thus, it may be a favorable choice as an initial therapy for such patients. Here, we report a case of recurrent gastric cancer with bone marrow metastasis with severe MAHA and thrombocytopenia successfully treated with high-dose 5-FU infusion followed by capecitabine.


  Case Report Top


This patient was a 61-year-old male with a history of gastric adenocarcinoma diagnosed in August 2013 and s/p radical subtotal gastrectomy + B-II reconstruction in August 2013, pT1bN0, cM0, Stage IA. In March 2018, he presented with general malaise and bone pain. Blood tests showed a typical presentation of hemolytic anemia including a hemoglobin (Hb) level of 6.8 g/dL, reticulocyte percentage of 6.65%, haptoglobin level of <5.83 mg/dL, total bilirubin level of 2.2 mg/dL, lactate dehydrogenase level of 544 IU/L, thrombocytopenia of 16 × 103/uL, and elevated alkaline phosphatase level of 1416 IU/L. A peripheral blood smear showed fragmented red blood cells 2+ (1–2/100 × 10 field), numerous normoblasts, and true thrombocytopenia. We immediately performed a bone marrow examination, which revealed numerous tumor nests. Because of his prior history of gastric cancer, cancer-associated MAHA was considered instead of thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. Esophagogastroduodenoscopy showed a gastric ulcer over the B-II anastomosis site. The pathology of the biopsy revealed no malignancy. A bone marrow biopsy yielded diffuse infiltration of polygonal, signet-ring tumor cells with hyperchromatic nuclei, and vacuolated cytoplasm arranged in nests. Immunohistochemical analysis showed cytokeratin (+), thyroid transcription factor-1 (−), CDX-2 (+, focal and weak), and human epidermal growth factor receptor-2 (−, score 0). Overall, the findings suggested metastatic adenocarcinoma of gastric origin. He was then treated with a 48-h infusion of high-dose 5-FU (2400 mg/m2) and leucovorin (LV) (400 mg/m2). Ten days later, we also administered low-dose oral capecitabine (1500 mg/day) as maintenance therapy. Two weeks after starting chemotherapy, his Hb level increased to 8.9 g/dL, and platelet count increased to 46 × 103/uL without transfusion support. Six weeks later, his blood cell count became normal. Oral capecitabine (1500–1600 mg/day) was continued for 1 year, and his complete blood cell count remained normal during this period. However, gastric cancer progressed with the recurrence of MAHA afterward, and he is now under platinum-based salvage chemotherapy.


  Discussion Top


MAHA is a rare but severe complication of gastric cancer. Effective chemotherapy for the underlying malignancy may be the only way to control MAHA. However, the myelosuppressive effect of most combination chemotherapies may prevent their use in the clinical setting of MAHA.

On reviewing the literature, mainly from Japan, patients with gastric cancer with MAHA and thrombocytopenia have been reported to be successfully treated using 5-FU-containing regimens.[4],[5] Yeh,[4] Hung,[6] and Noda et al.[7] reported a successful initial treatment of patients with gastric cancer, MAHA, and thrombocytopenia with aggressive chemotherapy [Table 1]. A retrospective study of 19 patients with advanced gastric cancer with MAHA and thrombocytopenia as the predominant feature confirmed that high-dose 5-FU/LV, a nonmyelosuppressive dosing schedule of 5-FU, is a safe and effective first-line therapy.[6] In addition, Tokar et al.[8] used a continuous infusion of 5-FU (200 mg/m2/day), another nonmyelosuppressive dosing schedule of 5-FU, as the initial treatment for patients with advanced gastric cancer presenting with MAHA.
Table 1: Different treatments and modalities for patients with advanced gastric cancer and microangiopathic hemolytic anemia

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According to previous retrospective studies, the response induced by a protracted infusion of 5-FU is usually short and persists for only a few weeks. Therefore, once the MAHA and thrombocytopenia symptoms are controlled, the addition of newer cytotoxic drugs may be necessary to consolidate the remission.[8] Initially, we planned to first administer high-dose 5-FU infusion, followed by combination chemotherapy if the MAHA and thrombocytopenia resolved, and the patient developed tolerance. However, because the subsequent subdural hematoma caused a relatively poor performance status, we only administered oral capecitabine as maintenance therapy. Unexpectedly, his cancer-associated MAHA and thrombocytopenia resolved without the recurrence for nearly 1 year [Figure 1] and [Figure 2].
Figure 1: Clinical response of the hemoglobin serum level of the patient HDFL = High dose of 5-FU/leucovorin, SDH = Subdural hematoma

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Figure 2: Clinical response of the platelet count of the patient . HDFL = High dose of 5-FU/leucovorin, SDH = Subdural hematoma

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  Conclusion Top


Cancer-associated MAHA and thrombocytopenia associated with advanced gastric cancer respond to initial treatment with a high dose of 5-FU/LV, which may persist under control with oral capecitabine maintenance therapy.[9]

Declaration of patient consent

We obtained the appropriate patient consent forms. In the form, the patient provided his consent for his clinical information to be reported in the journal. The patient understands that his name and initials will not be published, and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Etoh T, Baba H, Taketomi A, Nakashima H, Kohnoe S, Seo Y, et al. Diffuse bone metastasis with hematologic disorders from gastric cancer: Clinicopathological features and prognosis. Oncol Rep 1999;6:601-5.  Back to cited text no. 1
    
2.
Sastre J, Garcia-Saenz JA, Diaz-Rubio E. Chemotherapy for gastric cancer. World J Gastroenterol 2006;12:204-13.  Back to cited text no. 2
    
3.
Das P, Ajani JA. Gastric and gastro-oesophageal cancer therapy. Expert Opin Pharmacother 2005;6:2805-12.  Back to cited text no. 3
    
4.
Yeh KH, Cheng AL. Gastric cancer associated with acute disseminated intravascular coagulation: Successful initial treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin. Br J Haematol 1998;100:769-72.  Back to cited text no. 4
    
5.
Chao Y, Teng HC, Hung HC, King KL, Li CP, Chi KH, et al. Successful initial treatment with weekly etoposide, epirubicin, cisplatin, 5-fluorouracil and leucovorin chemotherapy in advanced gastric cancer patients with disseminated intravascular coagulation. Jpn J Clin Oncol 2000;30:122-5.  Back to cited text no. 5
    
6.
Huang TC, Yeh KH, Cheng AL, Hsu CH. Weekly 24-hour infusional 5-fluorouracil as initial treatment for advanced gastric cancer with acute disseminated intravascular coagulation. Anticancer Res 2008;28:1293-7.  Back to cited text no. 6
    
7.
Noda N, Sano T, Shirao K, Ono H, Katai H, Sasako M, et al. A case of bone marrow recurrence from gastric carcinoma after a nine-year disease-free interval. Jpn J Clin Oncol 1996;26:472-5.  Back to cited text no. 7
    
8.
Tokar M, Bobilev D, Ariad S, Geffen DB. Disseminated intravascular coagulation at presentation of advanced gastric cancer. Isr Med Assoc J 2006;8:853-5.  Back to cited text no. 8
    
9.
Hironaka SI, Boku N, Ohtsu A, Nagashima F, Sano Y, Muto M, et al. Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with bone metastasis. Gastric Cancer 2000;3:19-23.  Back to cited text no. 9
    


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