Japanese Journal of Clinical Oncology Advance Access originally published online on January 25, 2006
Japanese Journal of Clinical Oncology 2006 36(1):60-63; doi:10.1093/jjco/hyi219
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© 2006 Foundation for Promotion of Cancer Research
Case Report |
Neutropenic Colitis during Standard Dose Combination Chemotherapy with Nedaplatin and Irinotecan for Testicular Cancer
Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
For reprints and all correspondence: Ei-ichiro Takaoka, 2-12-16-1306 Minato, Chuo-ku, Tokyo 104-0043, Japan. E-mail: tach-tech-voice{at}mvb.biglobe.ne.jp
Received July 31, 2005; accepted November 7, 2005
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Abstract |
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A 54-year-old man received combination chemotherapy with nedaplatin and irinotecan as salvage chemotherapy for refractory non-seminomatous testicular cancer. The patient developed abdominal pain and high fever on Day 21 after the initiation of chemotherapy. Computed tomography revealed thickening of the terminal ileum wall and paralytic ileus. The patient recovered with intensive supportive management including broad-spectrum antibiotics, bowel rest with gastric intubation and intravenous
-globulin. Neutropenic colitis has been thought to be a serious gastrointestinal complication associated with chemotherapy for hematological malignancy. The mortality rate is as high as 21–48% according to a recent review. The present case indicates that the neutropenic colitis can occur under neutropenic conditions induced by the standard-dose chemotherapy for solid cancer.
Key Words: solid cancer • chemotherapy • neutropenic colitis text
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INTRODUCTION |
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Neutropenic colitis is one of the serious complications of neutropenia; it is characterized by segmental cecal and ascending colon ulceration that may progress to necrosis, perforation and septicemia. Typical but non-specific clinical features are fever, watery diarrhea, and diffuse and cramping abdominal pain. The reported mortality rate ranges from 21 to 48% (1).
Neutropenic colitis has been known as a complication of chemotherapy for hematological malignancy, but it is thought to be rare in patients with solid cancer. However, with introduction of intensified chemotherapy along with the use of new anti-cancer drugs, this complication has been reported with increasing frequency. Here, we report a case of neutropenic colitis during combination therapy with nedaplatin and irinotecan for testicular cancer.
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CASE REPORT |
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A 54-year-old man with testicular cancer that had metastasized to the lungs had previously been treated with five cycles of cisplatin-containing regimens (three courses of cisplatin and etoposide and two courses of cisplatin, ifosfamide and etoposide) in another hospital. Because the serum human chorionic gonadotropin (hCG) levels increased after the last chemotherapy, he was referred to the Tsukuba University Hospital for additional treatment. On admission, the serum hCG level was 11 mIU/ml and the
-fetoprotein level was normal. The radiological examination revealed a solitary brain metastasis in addition to multiple lung metastases. The patient underwent stereotactic radiotherapy for the brain metastasis, and it provided good tumor control. However, the subsequent salvage chemotherapy with two courses of paclitaxel, ifosfamide and cisplatin (2), and two courses of gemcitabine and paclitaxel (3) failed to achieve tumor marker normalization. The serum hCG levels increased to 950 mIU/ml 
1 month after the last chemotherapy. During the salvage chemotherapy, the patient did not experience gastrointestinal symptoms suggesting enterocolitis. We started combination chemotherapy with nedaplatin and irinotecan for this highly chemo-refractory case. The chemotherapeutic regimen followed that originally reported by Miki et al. Briefly, the treatment consisted of 100 mg/m2 irinotecan on Day 1 and Day 15, and 100 mg/m2 nedaplatin on Day 1 every 4 weeks. We used ‘Hangeshashinto’, a Chinese medicine at 7.5 g per day for 7 days every 2 weeks to prevent diarrhea due to irinotecan (4). The patient was free from the gastrointestinal symptoms except for the mild nausea and appetite loss until Day 20. On Day 21, he suddenly began to complain of abdominal pain, watery diarrhea and a fever over 39°C. The white blood cell count decreased to 600/mm3. The KUB showed a nearly gas-less pattern except for the segmental dilatation in the ascending colon shown in Fig. 1A. Despite administration of intravenous cefozopran hydrochloride (CZOP) and subcutaneous recombinant granulocyte colony-stimulating factor (G-CSF), the symptoms became worse. Physical examination revealed decreased bowel sounds, generalized abdominal tenderness and distention. The abdominal computed tomography (CT) on Day 22 showed marked bowel distention accompanied by thickening of the wall of the terminal ileum (Fig. 1B). Based on the physical and radiological findings, the clinical diagnosis of neutropenic colitis was made. We began to add further therapies consisting of bowel rest with a gastric tube, intravenous and intragastric tubal administration of vancomycin hydrochloride (VCM) for coverage of MRSA and intravenous -globulin. Because the patient was hemodynamically stable with aggressive supportive care, a surgical procedure was not indicated. The abdominal pain and watery diarrhea improved with the recovery of the white blood cell count. The plain abdominal X-ray findings were normalized. The abdominal CT on Day 29 revealed apparent improvement of the thickening of the ileum wall (Fig. 1C). Repeated blood and stool cultures failed to detect a specific organism. The patient made a good recovery from the complication. Because the hCG levels decreased to 13 mIU/ml after one course of nedaplatin and irinotecan, we elected to continue this combination chemotherapy. The second cycle was performed with prophylactic oral vancomycin. There were no clinical signs and symptoms suggesting colitis in the second course. The hCG levels decreased to 19 mIU/ml, but they subsequently increased again. The patient suffered from cancer progression with lung metastases and died 4 months later. Figure 2 illustrates the clinical course of the present case.
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DISCUSSION |
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Neutropenic colitis is a clinicopathological condition characterized by a septic or inflammatory abdominal process that may involve the cecum, colon and terminal part of the ileum in patients with neutropenia (1). The temporal association of administration of cytotoxic agents with the subsequent onset of neutropenic colitis suggests that drug-induced mucosal injury plays a significant role in this disease. Severe neutropenia by itself may, through unknown mechanism, cause colonic mucosal ulceration, as observed in cyclic neutropenia. Other precipitating factors contributing to mucosal damage include local bacterial of fungal infection with mucosal injury, necrosis of mural leukemic infiltrates, mural hemorrhage caused by severe thrombocytopenia, instrumentation, stasis of bowel contents with epithelial erosion and mucosal ischemia from sepsis-induced hypotention (5). The common pathological findings are the edema of mucosa or entire intestinal wall, mucosal ulceration, focal hemorrhage and transmural necrosis. Several mechanisms are considered to be involved in the development of neutropenic colitis. They include the direct toxicity of the anti-cancer drugs, the impaired granulocytic reaction and the reduced blood supply to the distended colon. As a result, the compromised systemic and local host defenses permit the persistence and penetration of an intestinal organism in the bowel wall (1). The disease was originally described in cases of hematological malignancies of children (6). However, with the introduction of intensified chemotherapy and new anti-cancer drugs, neutropenic colitis has been seen in adult patients receiving chemotherapy for solid cancer. We previously reported a testicular cancer patient who developed neutropenic colitis during high-dose chemotherapy with autologous blood stem cell transplantation (ABSCT) (7). Boggio et al. also reported three cases of the neutropenic colitis during ABSCT for metastatic breast cancer (8). More recently, this serious complication has been observed during standard-dose chemotherapy for solid cancer. The chemotherapies used in the reported cases were docetaxel combined with vinorelbine (9), vinorelbine as a single agent (10) and the combination of paclitaxel and doxorubicin (11). Kushner et al. reported three cases of neutropenic colitis that developed in combination chemotherapy using irinotecan or topotecan plus high-dose cyclophosphamide for neuroblastoma (12). However, to our knowledge, the present case is the first report of neutropenic colitis during standard-dose combination chemotherapy of nedaplatin and irinotecan. The common physical findings of the syndrome are fever, watery diarrhea, abdominal distension, diffuse abdominal pain and tenderness. The plain abdominal X-ray may show paralytic ileus or small bowel obstruction, a paucity of gas in the right lower quadrant, or a dilated, fluid-filled cecum, but the findings are non-specific and rarely helpful in the diagnosis. Ultrasonography and CT are more helpful. Ultrasonography may reveal an enlarged cecum with characteristic echogenic thickening of the mucosa, with or without fluid collection. Abdominal CT may show thickening of the right colonic wall [>4 mm in a distended bowel segment is considered abnormal (13)], pneumatosis intestinalis and perienteric soft tissue stranding (1,5,13). Part of the differential diagnosis for this clinical picture includes pseudomembranous colitis and ischemic colitis (5), lymphomatous or leukemic intramural deposits and hemorrhage, an abscess related to appendicitis (13). The optimal management of neutropenic colitis ranges from intensive supportive care to emergency surgery. Supportive care consists of bowel rest with nasogastric decompression, adequate fluid replacement, and broad-spectrum antibiotics. Shamberger et al. pointed out that surgical intervention should be considered in case of persistent gastrointestinal bleeding, intestinal perforation and clinical deterioration during medical therapy (6). Despite intensive supportive care or surgery, the reported mortality rates of neutropenic colitis were high, ranging from 21 to 48% (1). In the present case, the clinical features and radiological findings were compatible with those of cases reported in the literature. This case demonstrates that neutropenic colitis may occur in patients receiving standard-dose chemotherapy for solid cancer. Prompt recognition of the predicting signs such as massive watery diarrhea, development of paralytic ileus and thickening of the colon wall is a key to appropriate management of this serious syndrome.
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References |
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