Nine weeks versus 1 year adjuvant trastuzumab in patients with early breast cancer: an observational study by the Turkish Oncology Group (TOG).

BACKGROUND: Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey. METHODS: Records of 680 patients with HER2-positive early breast cancer who received adjuvant trastuzumab plus chemotherapy were obtained and patients were followed up to compare the disease-free survival (DFS) outcome of 9 weeks versus 1 year trastuzumab. RESULTS: Nine weeks and 1 year trastuzumab was given to 202 (29.7 %) and 478 (70.3 %) patients, respectively. There was a significantly lower rate of patients with negative lymph nodes in the 9-week trastuzumab group. At median 3 years of follow-up from the date of starting trastuzumab, the DFS rates were 88.6 and 85.6 %, respectively (p = 0.670). When adjusted for all the prognostic factors that were significant on univariate analysis, again there was no significant difference in DFS between the groups (HR 0.675; 95 % CI 0.370-1.231; p = 0.200). Cardiac toxicity defined as a ≥15 % decrease in LVEF was significantly higher in the 1-year trastuzumab group (1.88 % versus none for 1-year and 9-week trastuzumab groups, respectively; p = 0.050). CONCLUSION: The results of this observational study suggest that DFS outcome of 9 weeks of adjuvant trastuzumab may be comparable to 1 year adjuvant trastuzumab: this needs confirmation by randomized trials.

Synchronous tumors of the female genital tract: a 20-year experience in a single center.

OBJECTIVE: To evaluate the clinicopathological characteristics and the clinical outcome of synchronous malignant neoplasms of the female reproductive tract. MATERIAL AND METHODS: Patients who were operated and diagnosed with synchronous malignant tumor of the genital system (n = 25) at the Dokuz Eylul University Department of Obstetrics and Gynecology Gynecologic Oncology Unit between 1992 and 2012 were included into this study. Recurrent, metastatic and metachronously detected tumors were not included. Age at diagnosis, parity menopausal status, hormone use, presenting sign or symptoms and the clinical outcomes were evaluated. RESULTS: 20 of 25 patients had endometrial-ovarian cancer. The mean age at diagnosis was 53,6 years. The most common presenting symptom was abnormal uterine bleeding. The median follow-up duration for all patients was 69 months. Overall survival for all patients was 87 months and 81 months for patients with endometrial-ovarian cancer 5-year survival rate was 73% for all patients and 68% for patients with endometrial-ovarian cancer. CONCLUSIONS: Endometrial-ovarian cancer togetherness is the most common in synchronous gynecologic malignancies. They occur at a younger age and have more favorable prognosis than metastatic primary gynecologic tumors.

A cross-sectional survey of the diagnosis and management of bone metastasis in breast cancer patients in Turkey.

PURPOSE: This study aimed to report the practice of managing breast cancer with bone metastasis in Turkey and to determine the adherence to the British Association of Surgical Oncology (BASO) guidelines. METHODS: This multicenter, cross-sectional epidemiological survey was conducted in 38 centers across Turkey. Data from 1,026 breast cancer patients with bone metastases (mean age 54.0 ± 11.9 years) were analyzed. RESULTS: Over 30 % of patients had a diagnosis of metastatic breast cancer (stage IV) at the time of primary diagnosis. The imaging modalities used for diagnosing bone metastases were bone scintigraphy (57.8 %), radiography (22.8 %), and bone survey (4.4 %). Tumor markers were detected in 94.9 %, and markers of bone metabolism were measured in 90.4 % of patients. A total of 3.5 % of patients underwent surgery for bone metastasis, 26.4 % underwent palliative chemotherapy (most commonly docetaxel + capecitabine), and 56.5 % endured radiotherapy. Most patients (96 %) also received bisphosphonate. Radiography, bone scintigraphy, and CT were the main imaging tools used for postoperative follow-up of bone metastasis. Our results were >95 % in line with the BASO guidelines for the management of bone metastasis, except that interventional procedures, such as biopsy, were applied less frequently in our survey. CONCLUSIONS: The diagnosis and management practices of breast cancer with bone metastasis in Turkey were generally compatible with international guidelines. However, the awareness and knowledge of physicians on the current guidelines should be increased, and equipment for the appropriate interventional procedures should be provided in every clinic to obtain optimal and standard management of bone metastases.

Evaluation of Neoadjuvant Chemotherapy Response with Dynamic Contrast Enhanced Breast Magnetic Resonance Imaging in Locally Advanced Invasive Breast Cancer.

OBJECTIVE: The reliability of traditional methods such as physical examination, ultrasonography (US) and mammography is limited in determining the type of treatment response in patients with neoadjuvant chemotherapy (NAC) application for locally advanced breast cancer (LABC). Dynamic contrast-enhanced magnetic resonance imaging (MRI) is gaining popularity in the evaluation of NAC response. This study aimed to compare NAC response as determined by dynamic contrast-enhanced breast MRI in patients with LABC to histopathology that is the gold standard; and evaluate the compatibility of MRI, mammography and US with response types. MATERIALS AND METHODS: The US, mammography and MRI findings of 38 patients who received NAC with a diagnosis of locally advanced breast cancer and surgical treatment were retrospectively analyzed and compared to histopathology results. Type of response to treatment was determined according to the "Criteria in Solid Tumors Response Evolution 1.1" by mammography, US and MRI criteria. The relationship between response types as defined by all three imaging modalities and histopathology were evaluated, and the correlation of response type as detected by MRI and pathological response and histopathological type of breast cancer was further determined. For statistical analysis, the chi-square, paired t test, correlation and kappa tests were used. RESULTS: There is a statistical moderate positive correlation between response type according to pathology and MRI (kappa: 0.63). There was a weak correlation between response type according to mammography or US and according to pathology (kappa: 0.2). When the distribution of treatment response by MRI is stratified according to histopathological types, partial response was higher in all histopathological types similar to the type of pathologic response. When compared with pathology MRI detected treatment response accurately in 84.2% of the patients. CONCLUSION: Dynamic contrast-enhanced breast MRI appears to be a more effective method than mammography or US in the evaluation of response to neoadjuvant chemotherapy. MRI evaluation of LABC is accepted as the appropriate radiological approach.

Invasive micropapillary carcinoma of the breast: a clinicopathologic study of 103 cases of an unusual and highly aggressive variant of breast carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c-erb-B2 overexpression of tumors were re-evaluated. Mann-Whitney U, chi-squared, Kaplan-Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high-grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c-erbB-2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c-erb-B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log-rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c-erb-B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.

The Roles of Epithelial-to-Mesenchymal Transition (EMT) and Mesenchymal-to-Epithelial Transition (MET) in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment.

Many studies have revealed molecular connections between breast and bone. Genes, important in the control of bone remodeling, such as receptor activator of nuclear kappa (RANK), receptor activator of nuclear kappa ligand (RANKL), vitamin D, bone sialoprotein (BSP), osteopontin (OPN), and calcitonin, are expressed in breast cancer and lactating breast. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) effectors play critical roles during embryonic development, postnatal growth, and epithelial homeostasis, but also are involved in a number of pathological conditions, including wound repair, fibrosis, inflammation, as well as cancer progression and bone metastasis. Transforming growth factor ß (TGFß), insulin-like growth factor I & II (IGF I & II), platelet-derived growth factor (PDGF), parathyroid hormone-related protein (PTH(rP)), vascular endothelial growth factor (VEGF), epithelial growth factors II/I (ErbB/EGF), interleukin 6 (IL-6), IL-8, IL-11, IL-1, integrin αvß3, matrix metalloproteinases (MMPs), catepsin K, hypoxia, notch, Wnt, bone morphogenetic proteins (BMP), and hedgehog signaling pathways are important EMT and MET effectors identified in the bone microenviroment facilitating bone metastasis formation. Recently, Runx2, an essential transcription factor in the regulation of mesenchymal cell differentiation into the osteoblast lineage and proper bone development, is also well-recognized for its expression in breast cancer cells promoting osteolytic bone metastasis. Understanding the precise mechanisms of EMT and MET in the pathogenesis of breast cancer bone metastasis can inform the direction of therapeutic intervention and possibly prevention.

Systemic treatment of neuroendocrine tumors with hepatic metastases.

Neuroendocrine tumors, 1-2% of all malignancies, are relatively slow-growing neoplasms. The majority of neuroendocrine tumors belong to the World Health Organization Group 2 with well-differentiated endocrine carcinomas, but some tumors can be aggressive. The most common are gastroenteropancreatic-neuroendocrine tumors, followed by bronchopulmonary neuroendocrine tumors; less frequent locations are the ovaries, testis and hepatobiliary locations. They can be either non-functioning tumors with symptoms related to mass effects and malignant tumor disease or functioning tumors with specific hormones/neuropeptides autonomously secreted to induce specific clinical syndromes. Localized neuroendocrine tumors are less frequent than metastatic ones; in fact, up to 75% of patients with small bowel neuroendocrine tumors and 30-85% of pancreatic neuroendocrine tumors present with liver metastases either at the time of diagnosis or during the course of the disease. The predominant metastatic site is the liver, which is the best prognostic marker of survival regardless of the primary site. If surgical resection or interventional therapies of the hepatic tumor burden are not feasible, or if the metastases are not confined to the liver, systemic treatment remains the only option. None of the systemic therapies is liver-specific, but rather acts on all metastatic sites. The lack of prospective studies comparing different treatment modalities in homogeneous cohorts of patients makes the best treatment strategy poorly defined. Standard systemic therapy options are somatostatin analogues (octreotide and lanreotide), interferon-α and chemotherapy. Somatostatin analogues not only control symptoms related to functioning tumors but tumor growth as well. Because of the studies challenging its efficacy, as well as the potential for side effects, the more widespread acceptance of interferon-α in the treatment of metastatic neuroendocrine tumors has been limited. Well-differentiated neuroendocrine tumors do not show high sensitivity to chemotherapy because of their low mitotic rates, high levels of antiapoptotic protein bcl-2 and increased expression of the multi-drug resistant gene. Traditional chemotherapeutic agents are streptozotocin in combination with 5-fluorouracil or doxorubicin, or to some extent dacarbazine. Temozolomide, capecitabine and oxaliplatin, as monoagents or in combination therapy, show efficacy in phase II trials. Patients with poorly differentiated neuroendocrine tumor, regardless of the primary tumor localization, are candidates for cisplatin and etoposide chemotherapy regimen. Peptide receptor radionuclide therapy is reported to be an effective treatment option for patients with good performance status and high somatostatin-receptor scintigraphy uptake as well as without major liver involvement. Basic fibroblast growth factor, vascular endothelial growth factor, platelet-derived growth factor, transforming growth factor alpha and beta, insulin-like growth factor type 1, epidermal growth factor, stem cell factor (c-kit), and corresponding receptors have been shown to be expressed in Neuroendocrine tumors. Current phase II-III clinical trials with molecular-targeted therapies revealed promising agents such as everolimus (RAD001), an oral mTOR inhibitor, and sunitinib malate (SU-11248), an oral multitargeted tyrosine kinase inhibitor against vascular endothelial growth factor receptors, platelet-derived growth factor receptors, c-kit receptors, glial cell linederived neurotrophic factor, and FMS-like tyrosine kinase-3 (Flt 3), which were approved for the treatment of advanced pancreatic neuroendocrine tumors. Ongoing clinical trials with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, will further define the role of angiogenesis inhibitors in advanced intestinal neuroendocrine tumors. Various further novel strategies of targeted therapy and microRNA-regulated pathways in neuroendocrine tumors are under development.

A patient with nonfunctional pancreatic neuroendocrine tumor and incidental metachronous colon carcinoma detected by positron emission tomography: case report.

Pancreatic neuroendocrine tumors constitute about 2% of all gastrointestinal neoplasms. Approximately half of the pancreatic euroendocrine tumors are nonfunctional. Due to lack of specific symptoms, most patients with nonfunctional pancreatic neuroendocrine tumors present with locally advanced or metastatic disease. Second primary malignancies are seen very rarely in these patients. Colon carcinoma ranks third in frequency among primary sites of cancer in both men and women in western countries. Presence of a metachronous colon adenocarcinoma in a patient with nonfunctional pancreatic neuroendocrine tumor has not been reported before. We present a patient who had an asymptomatic mass in the head of the pancreas, detected by ultrasonography in 1996. The patient did not consent to operation. In 2002, after the diagnosis of an unresectable, nonfunctional pancreatic neuroendocrine tumor, interferon alpha- 2b and octreotide were started. A year after biological treatment, he refused further treatment. In 2004, during the evaluation of dissemination of the asymptomatic disease, positron emission tomography revealed a high uptake by the descending colon despite the failure of other imaging methods. After surgery for operable colon carcinoma, the patient received chemotherapy and biological therapy for both tumors. Since 2005, he has been doing well without any further treatment thus far. In conclusion, computerized tomography/magnetic resonance imaging and octreotide scintigraphy may be insufficient to show disseminated disease and asymptomatic second primary malignancies. Therefore, positron emission tomography is a valuable promising option for the evaluation of gastroenteropancreatic neuroendocrine tumors and concomitant or metachronous malignancies. Lifelong follow-up by a multidisciplinary oncology team is needed so that a long-term survival can be achieved with integrated multimodal systemic treatment approaches.

Relation of body mass index (BMI) to disease free (DFS) and distant disease free survivals (DDFS) among Turkish women with operable breast carcinoma.

BACKGROUND: The correlation between body mass index (BMI) and patient and tumor characteristics related to prognosis has not been well explored and may help to elucidate the mechanisms involved in the carcinogenesis. Because of the equivocal, inconsistent and uncertain research results as well as racial and ethnic differences, we aimed to evaluate the prognostic significance of high BMI in Turkish women with operable breast carcinoma. METHODS: Two hundred and sixty-six patients who had operable invasive breast carcinoma diagnosed from 2000 through 2004 in a single institution were evaluated for their demographic features, BMI, histopathological/immunohistochemical examinations and treatments. Quetelet BMI [weight (kg)/height (m)2] categories were selected according to the World Health Organization definition. Disease free survival (DSF) as well as distant disease free survival (DDSF) analyses were performed to identify independent prognostic factors. RESULTS: Post-menopausal patients were significantly in the higher quartile of BMI than pre-menopausal patients (P = 0.003). While post-menopausal obese patients had worse DSF and DDFS (P = 0.001), vascular invasion was the independent prognostic factor for both survival indices (P = 0.031). CONCLUSIONS: Post-menopausal obese Turkish women are at increased risk of developing breast tumors with aggressive phenotype and obesity is a strong predictor of poor DSF and DDFS. Preventive strategies to reduce not only the prevalence of obesity and breast cancer but also the mortality must be recognized as the cost-effective public-health policy for Turkey.

Gastric carcinoma during pregnancy: report of a case.

BACKGROUND/AIMS: Gastric cancer in pregnancy is extremely rare and often diagnosed at advanced stages. Well-recognized pregnancy-related symptoms, such as nausea and epigastric discomfort, can be the first symptoms of gastric cancer. Thus, the diagnosis of gastric cancer in pregnancy is difficult. We herein report a case of gastric cancer in pregnancy to alert clinicians to this rare possibility. MATERIALS AND METHODS: A 22-year- old nulliparous woman was examined by a gynecologist with a complaint of low abdominal pain. An abdominal ultrasound of the patient revealed 7th week of gestation and also showed massive ascites. She was referred to a hospital for further evaluation. Her other symptoms included loss of appetite, early satiety, and postprandial fullness. Gastroscopy demonstrated a tumor originating from the cardia and invading throughout the distal corpus. The histopathological diagnosis was gastric carcinoma with signet ring cells and her pregnancy was terminated. An explorative laparotomy revealed an unresectable gastric cancer and multiple peritoneal implants. Tumoral invasion was detected in pancreas and spleen. She was admitted to the medical oncology clinic and received a palliative chemotherapy. Bilateral double-J-stent placement was performed because of obstructive uropathy. A nasogastric tube was inserted for intestinal decompression, and total parenteral nutrition was administered. An adequate pain medication was given. To date (3 months after the diagnosis) the patient has been well without any signs of progression. CONCLUSION: Early diagnosis of gastric cancer is very important for a better outcome. The diagnosis may be delayed because mild gastrointestinal symptoms are common during pregnancy. Clinicians should take this into consideration in the differential diagnosis of persistent epigastric complaint during pregnancy. Suspicion and early upper gastrointestinal endoscopy are necessary.

The effect of anthracycline-based (epirubicin) adjuvant chemotherapy on plasma TAFI and PAI-1 levels in operable breast cancer.

An increased incidence of thromboembolic events has been described in women receiving systemic chemotherapy for breast cancer. The effect of anthracycline-based adjuvant chemotherapy regimens on fibrinolytic system markers of plasminogen activator inhibitor-1 (PAI-1) and thrombin activitable fibrinolysis inhibitor (TAFI) was investigated in patients with operable breast cancer. Twenty-four patients with operable breast cancer (median age, 54.5 years; range, 37-72 years) enrolled in our study. Stage I-II and stage IIIA cases received EC (Epirubicin 90 mg/m(2)/d1, I.V. and cyclophosphamide 600 mg/m(2)/d1, I.V.) and FEC (5-fluorouracil 500 mg/m(2)/d1, I.V., epirubicin 100 mg/m(2)/d1, I.V., and cyclophosphamide 500 mg/m(2)/d1, I.V.) as an adjuvant chemotherapy regimen, respectively. Each group consisted of 12 patients. Blood samples were obtained at baseline and just before the third cycle of EC and fourth cycle of FEC chemotherapy regimens. Plasma TAFI antigen and PAI-1 levels did not disclose any statistical difference between basal and postchemotherapy levels within each group and between two groups. Although postchemotherapy D-dimer levels were statistically higher in the FEC group than in the EC group, results in both groups were within normal ranges. More studies concerning the role of fibrinolytic system in breast cancer patients receiving chemotherapy, probably including cases with advanced stage and with different chemotherapy regimens and dose intensities, are needed.

Toxicity induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene and the protective effects of selenium in Wistar rats.

7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA (12 mg). In the Se group, rats received 20 microg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA-Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA-Se-treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA-Se-treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA.

False negative bone scintigraphy in a patient with primary breast cancer: a possible transient phenomenon of bisphosphonate (alendronate) treatment.

Breast cancer is the most common cancer and the second leading cause of cancer deaths among women in developed countries. Bone is a frequent site of metastatic disease with a stage-dependent incidence. Most women with breast cancer are at risk of osteoporosis due to their age or their breast cancer treatment. Scintigraphy enables imaging of the entire skeleton with high sensitivity but limited specificity. The false positive rate varies from 1.6% to as high as 22%, while the false negative rate varies from 0.96% to 13%. We observed a 70-year-old woman with a diagnosis of breast cancer and a false negative bone scan despite extensive bone metastases. She was under alendronate treatment for osteoporosis at the time. The false negative finding might be due to a transient phenomenon of alendronate, a bisphosphonate cleared from the plasma by uptake into bone and by renal excretion. 99mTc-MDP is eliminated via the same pathways, and therefore competition may occur between the two substances. Another possible explanation for the false negative bone scan could be that bone metastases, indicating hematogenous tumor spread, are detected earlier by CT scan or MRI than by bone scan. Breast cancer patients under bisphosphonate treatment for osteoporosis must be carefully evaluated for bone metastasis during radionuclide studies with 99mTc-MDP.

Primary non-hodgkin lymphoma of breast in a patient with rectal carcinoma and magnetic resonance spectroscopic examination.

A 62-year-old woman being treated for stage IIIC rectal adenocarcinoma was diagnosed with primary non-Hodgkin lymphoma of the breast after a 4-year follow-up. This case illustrates the importance of close and long-term follow-up as well as of differential diagnostic procedures for second primary malignancies after the initial diagnosis and treatment of a solid tumor.

The development of pulmonary adenocarcinoma in a patient with Job's syndrome, a rare immunodeficiency condition.

The hyperimmunoglobulin E (HIE) (Job's) syndrome often has it onset in childhood and is characterized by markedly elevated serum IgE levels, chronic dermatitis and recurrent pyogenic infections. Lymphoid malignancies have most commonly been associated with this syndrome while the first case in the literature of carcinoma associated with HIE syndrome was a squamous cell carcinoma of the vulva, described by Clark et al. in 1998. We observed a male patient with Job's syndrome diagnosed at age three who presented with bone pain and a metastatic epithelial tumor of the bone revealed by biopsy. Diagnostic procedures aimed at detecting the primary site showed multiple mediastinal lymph nodes with lung and liver metastases on computed tomography scans and an extradural spinal metastasis at the upper thoracic level on magnetic resonance imaging. Although the patient refused a bronchoscopic procedure, a diagnosis of pulmonary adenocarcinoma was established on the basis of sputum cytology and the clinical aspects of tumor extent. Intravenous corticosteroids and palliative radiotherapy were given for the spinal metastasis. Palliative chemotherapy could not be started because of the patient's poor performance status as well as nosocomial fungal pneumonia and pseudomonal urogenital infection with bacteremia. Despite the antifungal and broad-spectrum antimicrobial treatments, the patient died of pseudomonal sepsis.

Rapid tumor lysis syndrome in a patient with metastatic colon cancer as a complication of treatment with 5-fluorouracil/leucoverin and irinotecan.

Tumor lysis syndrome is a potentially fatal complication of anti-cancer therapy that is usually seen in patients with bulky, rapidly proliferating, treatment-sensitive tumors such as hematological malignancies, but it rarely occurs in a variety of solid tumors such as colorectal carcinoma. Combination chemotherapy with infusional 5-fluorouracil/leucoverin and irinotecan has been recently accepted as the first treatment option for metastatic colorectal cancer. We present a case of tumor lysis syndrome in a patient with metastatic colon carcinoma that occurred 72 hrs after the initial course of a combination chemotherapy with irinotecan and 5-fluorouracil/leucoverin. Despite the immediate treatment with aggressive hydration by a sodium bicarbonate infusion, followed by forced diuresis and uricolytic therapy, he died of a sudden cardiac arrest complicated by acute renal failure. Our case indicates that administration of 5-fluorouracil/leucoverin and irinotecan for bulky tumors of colorectal origin with a rapid doubling time may induce an acute tumor lysis syndrome, which necessitates frequent laboratory monitoring and a close follow-up of the patient as well as prompt initiation of appropriate therapeutic measures.