Hepatic artery infusion chemotherapy for metastatic colorectal carcinoma.

Hepatic metastases are a major cause of morbidity and will affect up to 80,000 new patients annually in the United States. Up to 20% of these patients will die with metastatic disease localized to the liver. Hepatic arterial infusion (HAI) therapy has a sound anatomical and pharmacological rationale.

Liver Metastases.

Liver metastases, especially from colorectal primary cancers, are treatable and potentially curable. Imaging techniques such as CT, MRI, and sonography have advanced in recent years and led to increased sensitivity and specificity in the diagnosis of liver metastases. Liver surgery also has been revolutionized in the past two decades.

Whole-Body FDG-PET in Patients with Recurrent Colorectal Carcinoma. A Comparative Study with CT.

Purpose: To assess the clinical accuracy of whole-body 2-[F-18]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in the diagnosis of recurrent colorectal carcinoma in comparison to conventional computed tomography (CT).Materials and methods: Forty patients with suspected recurrent colorectal carcinoma based on either progressive serial carcinoemrbyonic antigen (CEA) serum elevation or positive/equivocal CT findings underwent whole-body FDG-PET. PET results were compared with those of CT and correlated to the final histopathological and clinical findings.

Intra-abdominal fibrosis after systemic and intraperitoneal therapy containing fluoropyrimidines.

Background: Intra-abdominal and retroperitoneal fibrosis has been described as secondary to intraperitoneal (IP) administration of several chemotherapeutic agents, including carboplatin, mitoxantrone, and the combination of 5-fluorouracil and cisplatin. The IP administration of floxuridine (FUDR) is an effective and minimally toxic treatment for patients with metastases to the peritoneum. An increasing number of patients with colorectal, gastric, or ovarian carcinoma are treated with IP chemotherapy.

Levels of E2F-1 expression are higher in lung metastasis of colon cancer as compared with hepatic metastasis and correlate with levels of thymidylate synthase.

We recently reported that forced overexpression of the transcription factor E2F-1 in human HT-1080 fibrosarcoma cells resulted in corresponding high levels of thymidylate synthase (TS) and resistance to 5-fluoropyrimidines (D. Banerjee et al., Cancer Res.

Non-surgical treatment for liver metastases.

The liver is a common site for developing metastatic disease. Although any malignancy can spread to the liver, the direct passage of blood from the gastrointestinal tract to the liver via the portal circulation results in a high rate of liver metastasis from gastrointestinal tract tumours. Various radiographical tests including computed tomography and magnetic resonance imaging can detect the majority of liver metastases.

Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer.

Background: Two years after undergoing resection of liver metastases from colorectal cancer, about 65 percent of patients are alive and 25 percent are free of detectable disease. We tried to improve these outcomes by treating patients with hepatic arterial infusion of floxuridine plus systemic fluorouracil after liver resection.

Methods: We randomly assigned 156 patients at the time of resection of hepatic metastases from colorectal cancer to receive six cycles of hepatic arterial infusion with floxuridine and dexamethasone plus intravenous fluorouracil, with or without leucovorin, or six weeks of similar systemic therapy alone.

Utility of 18F-FDG positron emission tomography scanning on selection of patients for resection of hepatic colorectal metastases.

Background: Hepatectomy represents a standard and potentially curative therapy for hepatic colorectal metastases. However, up to two thirds of patients explored for resection are found to have unsuspected disease, which precludes resection.

Methods: In order to determine if 18F-FDG positron emission tomography (PET) scanning may prevent unnecessary surgery, a group of 40 patients being considered for hepatic resection but at high risk for unresectable disease by clinical criteria were subjected to whole body 18F-FDG-PET scanning.

Hepatic arterial chemotherapy in metastatic colorectal patients.

Hepatic metastases are a major cause of morbidity and mortality for patients with colorectal cancer (CRC). The rationale for hepatic arterial chemotherapy has both an anatomical and pharmacological basis. Several randomized clinical studies of fluoropyrimidine showed higher response rates in all trials when the drug was given as an hepatic arterial infusion (HAI) versus systemic administration.

5-fluorouracil-induced small bowel toxicity in patients with colorectal carcinoma.

Background: Diarrhea and oral mucositis are the most frequently reported gastrointestinal side effects caused by 5-fluorouracil (5-FU). Diarrhea may be severe in 10-30% of patients and is schedule-dependent. 5-FU-induced gastrointestinal toxicity predominantly affects the upper and the lower gastrointestinal tract.

Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma.

Hepatic metastases from colorectal carcinoma are common and may be resected for cure. The response of liver metastases to systemic chemotherapy is low. In contrast, hepatic arterial chemotherapy produces higher response rates than systemic chemotherapy, but randomized trials have not definitely proved a survival advantage because they allowed cross over.

Evaluation of chest computed tomography in the staging of patients with potentially resectable liver metastases from colorectal carcinoma.

Background: Chest computed tomography (CT) often is used to rule out lung metastases in patients with potentially resectable liver metastases from colorectal carcinoma. In the current study the authors evaluated whether CT of the chest was necessary in patients with a negative chest radiograph.

Methods: The authors performed a retrospective analysis of 202 patients with negative initial chest X-rays who were undergoing evaluation for potentially resectable liver metastases from colorectal carcinoma.

Phase I clinical and pharmacologic study of weekly cisplatin combined with weekly irinotecan in patients with advanced solid tumors.

Purpose: In vitro synergy between cisplatin and irinotecan (CPT-11) has been reported. We designed a combination schedule of these agents to maximize the potential for synergistic interaction.

Patients And Methods: To maximize the opportunity for synergy, we divided the cisplatin into four consecutive weekly treatments, followed by a 2-week rest.

In vitro detection of occult bone marrow metastases in patients with colorectal cancer hepatic metastases.

Purpose: The purpose of this study was to assess the immunocytochemical status of bone marrow aspirates from patients with clinically isolated hepatic metastases to test the hypothesis that such findings would allow improved patient selection for liver-directed treatment.

Methods: All patients had biopsy-proven or presumed colorectal cancer metastatic to the liver and were scheduled for an operative procedure for hepatic resection or for hepatic artery catheter and chemotherapy pump implant. Immunocytochemical analysis of bone marrow aspirate smears was performed with a panel of monoclonal antibodies directed toward cytokeratins, Lewis Y antigen and A-33 colorectal epitopes.

Mathematical model of 5-[125I]iodo-2'-deoxyuridine treatment: continuous infusion regimens for hepatic metastases.

Purpose: Due to the cytotoxicity of DNA-bound iodine-125, 5-[125I]Iodo-2'-deoxyuridine ([125I]IUdR), an analog of thymidine, has long been recognized as possessing therapeutic potential. In this work, the feasibility and potential effectiveness of hepatic artery infusion of [125I]IUdR is examined.

Methods: A mathematical model has been developed that simulates tumor growth and response to [125I]IUdR treatment.

Phase II trial of docetaxel (Taxotere) for untreated advanced colorectal carcinoma.

The antimicrotubule agent docetaxel (Taxotere), a semisynthetic taxoid, has demonstrated antitumor activity against colorectal cancer cell lines in vitro, and in murine tumor models. We sought to characterize its activity in a group of previously untreated patients with colorectal carcinoma. Eighteen previously untreated patients with advanced, measurable colorectal carcinoma were treated with a 60-min intravenous infusion of docetaxel with a dose of 100 mg/m2 administered every 21 days.

Higher levels of thymidylate synthase gene expression are observed in pulmonary as compared with hepatic metastases of colorectal adenocarcinoma.

Purpose: It has been observed previously that the pulmonary metastases of colorectal adenocarcinoma are less responsive to therapy with fluorouracil (FUra) as compared with other sites of metastasis (liver, local). To investigate the basis of this chemoresistance, the levels of thymidylate synthase (TS) mRNA and protein were measured, as TS expression has been shown to be predictive of response to therapy in colorectal cancer.

Materials And Methods: Tumors were obtained from 19 patients with metastatic colorectal cancer (12 hepatic and seven pulmonary).

Role of chest CT in patients with negative chest x-rays referred for hepatic colorectal metastases.

Background: Hepatic resection is the standard treatment for hepatic colorectal metastases. The lung represents the next most likely site, after the liver, of metastatic disease. Computed tomography (CT) of the chest is more sensitive than is chest x-ray in detecting metastatic lung lesions.

9-Aminocamptothecin by 72-hour continuous intravenous infusion is inactive in the treatment of patients with 5-fluorouracil-refractory colorectal carcinoma.

Background: 9-Aminocamptothecin (9AC) and its parent compound, camptothecin, have shown outstanding preclinical activity against colorectal carcinoma. Irinotecan (CPT-11), another camptothecin derivative, has demonstrated clinical activity in patients with 5-fluorouracil (5-FU)-refractory colorectal carcinoma.

Methods: The authors performed a Phase II trial of 9AC involving patients with measurable metastatic colorectal carcinoma who had progressed through only one prior regimen of 5-FU-based chemotherapy.

Adjuvant therapy of colorectal cancer.

Approximately 141,000 patients will develop colorectal cancer each year and 45% will have positive lymph nodes, one of the most significant predictors of survival. Now there is evidence that systemic chemotherapy with fluorouracil (FU) and leucovorin, levamisole, or FU and leucovorin with decrease recurrence and increase survival for patients with Dukes' C colon cancer. In patients with Dukes' B or C rectal cancer, combined radiation and FU increase survival and decrease local and distal recurrence.

Neutropenic enterocolitis in a patient with colorectal carcinoma: unusual course after treatment with 5-fluorouracil and leucovorin--a case report.

Background: Neutropenic enterocolitis is observed in approximately 25% of patients with acute leukemia, but has been reported rarely in patients with solid tumors. If treatment is not initiated promptly, the mortality is high. The incidence of this disease is rising in patients with hematologic malignancies.

Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for clinically resectable T3 rectal cancer.

Purpose: We report the downstaging, sphincter preservation, acute toxicity, and preliminary local control and survival results of preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and concurrent radiation therapy followed by postoperative LV/5-FU for treatment of patients with clinically resectable T3 rectal cancer.

Materials And Methods: A total of 32 patients received two monthly cycles of preoperative LV/5-FU (bolus daily X 5). Radiation therapy (5,040 cGy) began concurrently on day 1.