Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Capecitabine is a novel fluoropyrimidine carbamate, orally administered and rationally designed to undergo tumor-selective activation. Some studies have been proven it to be safe for outpatient treatment and to have significant antitumor activity in colorectal and breast cancer patients. Randomized trials of patients with advanced colorectal cancer using capecitabine versus Leucovorin (LV).5-FU were studied in two groups. Capecitabine results in both a higher response rate and a more favorable toxicity profile than LV.5-FU. In women aged 55 years or more with breast cancer, capecitabine showed at least comparable efficacy to CMF combination therapy. Capecitabine offers a new effective oral treatment option as a single agent for patients with advanced colorectal or breast cancer.
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PMID:[Capecitabine--a review of its antitumor activity and toxicity in clinical studies]. 1094 31

Raltitrexed (RTX) is an antifolate thymidylate synthase (TS) inhibitor that is effective for the treatment of advanced colorectal cancer and other solid tumors. However, a small minority of patients receiving RTX monotherapy will experience grade III/IV gastrointestinal toxicity that can be life-threatening, particularly if copresenting with neutropenia. Lack of vigilance in recognition and treatment of symptoms of toxicity or violations of protocol have led to treatment-related deaths in some hospitals. The safety of RTX could be improved if an effective rescue agent was available. Leucovorin (LV) is a reduced folate cofactor that competes with RTX for transport and polyglutamation in both tumor and normal tissues and thus has potential as a rescue agent. In vitro cell studies are presented suggesting that the growth-inhibitory, and potentially cytotoxic, effects of RTX on populations of viable cells can be reversed by the delayed administration of LV. The mechanisms involved are inhibition of further drug uptake and polyglutamation and a redistribution and/or reduction in the concentration of preformed raltitrexed polyglutamates. A more clinically relevant in vivo mouse model was used to test the hypothesis further. BALB/c mice treated with 100 mg/kg/day x 4 days of RTX were used as a model for gastrointestinal and bone marrow toxicity. LV (200 mg/kg), which was given after the onset of severe weight loss and diarrhea (twice daily, days 5-7), prevented further weight loss and induced earlier recovery. This was accompanied by improvement in the histological appearance of the intestine (day 7) and the concentration of neutrophils and platelets in the blood (day 9). BALB/c mice could not tolerate 100 mg/kg daily x 5 days unless LV (200 mg/kg twice daily) was given on days 6-8. Measurement of RTX (polyglutamates) by RIA after 100 mg/kg RTX daily (days 1-4) showed less drug in plasma (3-4-fold), liver (8-11-fold), kidney (3-4-fold), and small intestinal epithelium (3-4-fold) on day 7 in LV-treated mice (100 or 200 mg/kg twice daily) compared with controls. A single injection of 100 mg/kg RTX (day 1) gave plasma levels of 3-4 pmol/ml on day 4 that are more clinically relevant. Administration of LV (100 or 200 mg/kg; twice daily on days 4-6) reduced the RTX concentration in the liver 2-4-fold on days 7, 9, and 11 compared with controls. A model is proposed where LV and/or its anabolic products can compete with RTX uptake into tissues and interfere with the homeostatic regulation of RTX polyglutamates. These data support the use of LV rescue in the small minority of patients treated with RTX who present with a severe pattern of antiproliferative toxicities. The use of LV is not recommended routinely because the antitumor activity of RTX may similarly be reversed.
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PMID:Leucovorin rescue from raltitrexed (tomudex)-induced antiproliferative effects: in vitro cell line and in vivo mouse studies. 1099 57

A 55-year-old man had a metastasis in segment 3 of the liver 5 months after surgery for non-functioning islet cell carcinoma of the pancreas. The metastatic lesion increased in size in a short period, and other liver micro-metastases that could not be detected by imaging may exist, so hepatic arterial infusion chemotherapy was scheduled for 3 months. The patient underwent hepatic arterial infusion chemotherapy of 5-fluorouracil (250 mg/day/body for 5 days/week) and adriamycin (10 mg/day/body for 2 days/week) and cisplatin (10 mg/day/body for 5 days/week) and he was put on Leucovorin 30 mg/day as a biochemical modulator of 5-FU and tamoxifen 40 mg/day as a biochemical modulator of ADM. A total 6,000 mg of 5-FU, 100 mg of ADM and 240 mg of CDDP had been administered, until hepatic arterial infusion chemotherapy was discontinued because of complicated gastric ulcer. Three months later, the size of the metastatic liver tumor was reduced remarkably and no other metastasis was detected on CT scan, so he underwent partial hepatectomy of the metastatic lesion. No recurrence was found and he has survived in good physical condition during the follow-up period of 5 months after the second operation.
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PMID:[An effective case of hepatic arterial infusion chemotherapy based on biochemical modulation for hepatic recurrence of non-functioning islet cell carcinoma of the pancreas]. 1108 47

The aim of this randomized open-label study was to compare a bimonthly with a monthly regimen of 5-fluorouracil (5-FU) and leucovorin for the adjuvant treatment of colon and high-rectum adenocarcinoma. The bimonthly regimen was administered for 2 consecutive days every 14 days as d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 as a 2-hour infusion followed by 5-FU bolus of 400 mg/m2 and a 600 mg/m2 5-FU 22-hour continuous infusion (LVSFU2). In the monthly regimen, d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 15-minute infusion followed by a 400 mg/m2 15 minute 5-FU bolus was administered for 5 consecutive days every 28 days (FUFOL). Nine hundred five patients with recently resected stage B2 or C colon or high-rectum adenocarcinoma (inferior pole of the tumor subperitoneal) were recruited into the study. Patients were randomized in a 2 x 2 factorial design to receive either LV5FU2 or FUFOL for 24 or 36 weeks. Characteristics of the patients in the two different treatment groups were similar at baseline. Compliance was good. Mean 5-FU dose intensities were 930 mg/ m2/wk and 463 mg/m2/wk for LVSFU2 and FUFOL, respectively. The incidence of maximal grade III-IV toxicities for LVSFU2 and FUFOL was neutropenia 6% and 16% (P < .001), diarrhea 4% and 10% (P < .001), and mucositis 2% and 7% (P < .001), respectively. Maximum grade III-IV toxicities in the LV5FU2 treatment group were significantly lower than in the FUFOL group (10% v 26%; P < .001). Although patients in the LV5FU2 group received twice the dose of 5-FU compared with those in the FUFOL group, LV5FU2 was shown to be less toxic. Efficacy data will be available in 2001.
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PMID:Randomized adjuvant study comparing two schemes of 5-fluorouracil and leucovorin in stage B2 and C colon adenocarcinoma: study design and preliminary safety results. Groupe d'Etude et de Recherche Clinique en Oncologie Radiotherapies. 1127 88

We treated a patient with intra-peritoneal recurrent tumor from colon cancer who responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5-fluorouracil (5-FU). The patient was a 75-year-old man. He underwent resection of the transverse colon, sigmoid colon and distal stomach for colon and gastric cancers. Nine months after the operation, his CEA level increased to 39.5 ng/ml and a CT scan revealed an intra-peritoneal tumor measuring about 5 cm. He received chemotherapy of 30 mg/day of LV that was injected in a bolus and 500 mg/day of 5-FU that was given i.v. by continuous infusion for 10 days. At the end of 2 cycles of this regimen, CT scan demonstrated complete tumor remission and the patient's CEA level decreased to normal level. After an additional cycle of this regimen, he received modulated chemotherapy combined with l-Leucovorin and 5-FU as an outpatient. However, after 3 months of treatment, a recurrent tumor was detected in the same portion and the first regimen was re-started for 5 days. After 4 cycles of treatment the tumor disappeared completely from a CT scan. It is important to investigate effective regimens that do not reduce the quality of life of the patient. This clinical experience suggests that a low-dose LV/5-FU therapy may be beneficial to patients with recurrent colon cancer. Further investigation is necessary to establish an effective regimen that can be given for a long period without adverse effects on quality of life.
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PMID:[A case of intra-peritoneal recurrence of colon carcinoma that responded remarkably to combined therapy of low-dose leucovorin and 5-fluorouracil]. 1157 43

A 57-year-old female diagnosed with advanced gastric cancer with multiple organ metastases was treated by various intra-arterial chemotherapies. After surgical resection of the tumor, adjuvant chemotherapy was carried out. Continuously administered 5-fluorouracil of 250 mg/day made it possible to control the growth of the liver metastases. Extrahepatic metastases were kept under control by administering 30 mg of methotrexate, 750 mg of 5-fluorouracil and 30 mg of Leucovorin per/day/week, and 60 mg/day biweekly of cisplatinum via an abdominal artery infusion port. Owing to this multiple infusion route and chemotherapy regimen, the patient lived for 18 months after her first diagnosis of gastric cancer with multiple liver metastases. Although liver metastases may respond to hepatic arterial infusion chemotherapy, extrahepatic metastases lead to poor prognosis. Given the above results, intra-abdominal aorta chemotherapy may be effective for extrahepatic metastases since this method gives high concentration of the anticancer agents at tumor sites with a low incidence of side effects.
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PMID:[A case of advanced gastric cancer with multiple liver metastases partially responding to combination intra-arterial chemotherapy via the hepatic artery and abdominal aorta]. 1170 20

A 51-year-old man underwent right hemicolectomy due to ascending colon cancer with multiple liver metastases. Administration of modified pharmacokinetic modulating chemotherapy (PMC) using Leucovorin (intravenous infusion of 5-FU, 600 mg/m2/24 hours; oral administration of UFT, Taiho Pharmaceutical Co., Tokyo, Japan, 400 mg/day; and Isovorin, Wyeth Lederle Co., Tokyo Japan, 250 mg/body) was started postoperatively. Two months of modified PMC produced a drastic tumor reduction without any adverse reactions such as diarrhea or myelosuppression observed. At present the patient continues to tolerate the chemotherapy and is being followed as an outpatient clinic. This case suggests the usefulness of modified PMC using Leucovorin for progressive recurrent colon cancer.
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PMID:[A case of multiple liver metastases from colon cancer successfully treated with modified pharmacokinetic modulating chemotherapy using Leucovorin]. 1246 6

A 48-year-old male patient was admitted to our institution with left hypochondralgia. Preoperative serum CEA was 504 ng/ml. Under a radiological diagnosis of simultaneous double cancer of the pancreas and lung, resection was performed. Pathological study revealed primary pancreatic cancer with lung metastasis. After the operation, serum CEA fell to 55 ng/ml. Seventeen months later, bowel obstruction occurred and serum CEA was 140 ng/ml. One course of systemic chemotherapy, using the combination of CDDP, 5-FU and Leucovorin, was successful. After another three months, however, the same clinical symptoms occurred. With no response to the prior chemotherapy regimen, surgery was undertaken and a mass at the mesentery was removed. Fifty-nine months have passed since the initial operation and the patient is free of disease, though his serum CEA is around 50 ng/ml. In conclusion, there are cases of pancreatic cancer in which tumor dormancy can be achieved by postoperative 5-FU based chemotherapy.
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PMID:[Resection of pancreatic cancer and simultaneous lung metastasis--a case report of successful in tumor dormancy mainly by postoperative 5-fluorouracil-based chemotherapy]. 1248 80

Colorectal Cancer (CRC) is the most frequent digestive cancer in France and a major public health problem. The benefits of adjuvant chemotherapy after curative resection of Stage III CRC has been clearly demonstrated. For metastatic CRC, palliative chemotherapy allows an improvement in survival duration and quality of life compared with symptomatic treatment. 5-FU/Leucovorin chemotherapy (Mayo Clinic protocol and LV5FU2) is the standard adjuvant therapy. The addition of irinotecan (FOLFIRI) or oxyplatin (FOLFOX) to this regimen may improve response in palliative situations. These two regimens have shown their superiority to 5FU/Leucovorin in both tumor response and survival. A good objective response to palliative chemotherapy may allow for a secondary resection of hepatic metastases as part of a multidisciplinary approach. Current studies aim to define: 1) optimal treatment strategies (which drug protocols? in what order?) as they apply to tumor spread, drug toxicity profiles, the general state of the patient, and the desired therapeutic effect; 2) evaluation of new drugs and novel therapeutic approaches. Despite notable progress, the prognosis still remains grim with a survival of only 40% at 5 years. Any improvement in results will require not only an improvement in chemotherapy but also an improvement in methods of early diagnosis (systematic mass screening) which would permit the diagnosis of CRC at earlier stages where curative resection is feasible.
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PMID:[Chemotherapy for colorectal cancers]. 1270 55

Preclinical and clinical models have demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in primary and metastatic colorectal tumors. In preclinical models, there appears to be additive or synergistic effects when combining 5-Fluorouracil (5-FU) with nonsteroidal anti-inflammatory agents (NSAIDs) for the treatment of colorectal neoplasms. This data raised the question as to whether adding a COX-2 inhibitor to 5-FU-based regimens would increase the response rates with an acceptable toxicity profile in patients with metastatic colon cancer. In the current study, patients with metastatic colorectal cancer, who were either untreated or previously treated (more than 1 year ago) with adjuvant 5-FU and Leucovorin (LV) received 5-FU and LV (Mayo regimen) in addition to Rofecoxib. Tumor samples from all patients exhibited evidence of moderate COX-2 over-expression. 4 patients entered on the study developed upper gastrointestinal bleeding (grade III). Other toxicities included grade II stomatitis (3 patients), grade II thrombocytopenia (1 patient), grade II diarrhea (2 patients) and grade I nausea (1 patient). There were no partial or complete responses in the first 10 patients entered on the study so the study was terminated (probability of success < 0.3 with type 1 error of 0.05 and power of 0.8). Thus, Rofecoxib did not appear to increase antitumor activity and resulted in increased gastrointestinal toxicity when combined with 5-FU/LV. Future studies will need to consider the added gastrointestinal toxicity of Rofecoxib when combined with chemotherapy for the treatment of patients with colorectal cancer.
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PMID:Increased toxicity and lack of efficacy of Rofecoxib in combination with chemotherapy for treatment of metastatic colorectal cancer: A phase II study. 1506 99


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