Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biologic and antitumor activity of 5-azacytidine has been well demonstrated in the past. The drug at present is thought to be primarily cell cycle phase specific. This study was designed to eliminate undesirable side effects (mainly nausea and vomiting) occurring with a bolus dose and to confirm the recent findings of the relative stability of 5-azacytidine's solution with preserved biologic and antitumor activity. In the study we determined that a dose of 150 mg/m2/day given as a 120-hour continuous iv infusion and repeated at 28-day intervals produced safe, manageable, and reproducible toxicity. The drug was freshly prepared at 4-hour intervals. Eleven courses were administered to seven patients at this dose level and no patient experienced nausea or vomiting. Leukopenia was the major toxic effect. Antitumor activity was shown in one patient with colon cancer and another with American Burkitt's lymphoma.
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PMID:Phase I study of 5-azacytidine (NSC-102816) using 24-hour continuous infusion for 5 days. 5 88

Thirty-two patients with advanced carcinoma of the colon or rectum were given metronidazole orally at a dose of 500-1000 mg/m2 three times a day for 7 consecutive days every 6 weeks. The dose-limiting toxic effects consisted of severe nausea, vomiting, and major motor seizures. Mild peripheral neurotoxic effects were also noted. No objective responses were noted in any of the 32 patients treated. High-dose metronidazole would not seem to have any role in the treatment of advanced colorectal carcinoma and may cause serious neurotoxicity.
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PMID:Phase II study of metronidazole therapy for advanced colorectal carcinoma. 34 20

Patients with breast carcinoma metastatic to the colon generally present with multiple symptoms, usually pain, vomiting, nausea, and ascites. We describe a patient who presented only with persistent diarrhea, underwent surgery for colon cancer, and, on pathological evaluation of the surgical specimen, was found to have metastatic breast cancer affecting the colon. Metastatic breast cancer should therefore be suspected in patients with a history of breast cancer and diarrhea of unknown cause that is not accompanied by other symptoms. Evaluating such patients by colonoscopy and biopsy would provide important information relevant to choosing between colon surgery and systemic therapy.
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PMID:Metastatic breast carcinoma presenting as persistent diarrhea. 143 49

This phase I study investigated flavone acetic acid (FAA) given as a 12-h intravenous infusion every 3 weeks in the absence of urinary alkalinisation. Cohorts of three patients were treated at doses of 7, 10 and 13 g/m2. One subject had colon cancer; 5, renal cancer; and 3, lung cancer. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in four patients, 1 in two subjects and 2 in three cases. The maximum tolerated dose was 13 g/m2. The dose-limiting toxicities were WHO grade 3 hypotension and grade 3 diarrhoea. Other toxicities included lethargy and dizziness, nausea, temperature fluctuation, myalgia and dry mouth, but no significant myelosuppression was encountered. One patient receiving 10 g/m2 for renal cancer showed a partial response that lasted for 3 months and included the resolution of pulmonary and cutaneous metastases. The pharmacokinetics showed large interpatient variability. At 12-16 h post-infusion, the plasma elimination profile entered a plateau phase, with frequent increases in concentration suggesting enterohepatic recycling. Neither peak FAA levels nor AUC values were dose-dependent at the doses studied. Peak plasma levels were 101-402 micrograms/ml and AUC (0-48 h) values were 75-470 mg ml-1 min. Plasma protein binding varied with total concentration. Two metabolites were detected in the plasma, and both also underwent apparent enterohepatic recycling. Repeat dosing resulted in decreases of up to 48% in peak levels and AUC values for FAA in three of six patients. Of the total FAA dose, 39%-77% was excreted in the urine as FAA or metabolites within 2 days. The dose recommended for further phase II studies is 10 g/m2.
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PMID:A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. 155 Nov 73

Based on recent preclinical data suggesting synergism between 5-fluorouracil (5-FU) and interferon alpha (IFN-alpha) and clinical activity of the combination therapy in colon cancer, 14 patients with advanced gastric cancer were treated with combination therapy of 5-FU and recombinant interferon alpha-2b (rIFN alpha-2b) (Intron A, Schering, Kenilworth, NJ, U.S.A.). The maximum tolerated dose was 5-FU 750 mg/m2/day given as a continuous infusion daily for 5 days followed by weekly bolus injection of the same initial daily dose, plus rIFN alpha-2b 5 X 10(6) U given subcutaneously 3 times weekly starting day 1 of 5-FU infusion. The dose-limiting toxicities were fatigue/weakness, diarrhea, and neurologic toxicities such as somnolence and confusion. The other common side effects were nausea, fever, leukocytopenia, thrombocytopenia, and the darkening of the skin. Of 13 evaluable patients, 4 had a partial response (duration 6, 14, 24, and 28 weeks). These data suggest that combination therapy of 5-FU plus rIFN alpha-2b is tolerable and has manageable side effects in patients with advanced gastric cancer. Further Phase II study will be needed to define the antitumor activity of this combination.
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PMID:Combination of 5-fluorouracil and recombinant interferon alpha-2B in advanced gastric cancer. A phase I study. 155 2

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.
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PMID:A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy. 155 45

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.
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PMID:Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer. 159 14

The chemistry, pharmacology, pharmacokinetics, assay methodologies, adverse effects, and dosage of levamisole are described, and the clinical studies of levamisole therapy in patients with colorectal carcinoma are reviewed. Levamisole is a synthetic, orally active agent that has antihelmintic and immunomodulatory properties. It is capable of inducing T-cell differentiation and restoring depressed effector functions of peripheral lymphocytes and phagocytes to normal. The drug is well absorbed from the gastrointestinal tract after oral administration and is extensively metabolized by the liver. Gas chromatography and high-performance liquid chromatography are the most common methods used to measure concentrations of levamisole in biologic fluids. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with surgically resected Dukes stage C colon cancer; this combination is now recommended as standard therapy in these patients. Uses in patients with rectal carcinoma, Dukes stage B colon cancer, metastatic colon cancer, other malignancies, or nonmalignant disorders remain investigational. Common adverse effects include nausea, abdominal pain, vomiting, diarrhea, metallic or altered taste, flulike symptoms, mood elevation, insomnia, hyperalertness, dizziness, and headache. The most serious adverse effect associated with levamisole is granulocytopenia. The FDA-approved dosage of levamisole is 50 mg orally every eight hours for three days every two weeks. Levamisole therapy is to be initiated no earlier than 7 and no later than 30 days after surgery and is to be continued for one year. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with resected stage C colon cancer. Further research is needed to more clearly define the mechanism of action, optimum dose and scheduling, and clinical efficacy of levamisole in treating other malignancies.
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PMID:Levamisole in the adjuvant treatment of colon cancer. 200 37

We examined the quality of life in the arterial infusion chemotherapy of hepatocellular carcinoma patients using a questionnaire. The questionnaire used a category scale method of five grades. The questions about the quality of life covered ten areas for investigation (appetite, discomfort pain, nausea, daily activities, sleep, fatigue, time with family and friends, thinking about illness and confidence in the treatment). We added up scale points after one week and those after two weeks after the treatment. Patients after one-shot infusion showed aggravated scale points of anorexia and discomfort. Patients after transcatheter arterial embolization showed scale points of abdominal pain, general fatigue and discouragement about illness. Scale points in matters of thinking about illness and confidence in the treatment informed us about confidence in the course of treatment and comprehension of illness by cancer patients. How do we measure the quality of our care? This is difficult, but we thought the rate of being at home in survival might furnish us with much information in respect to the treatment and the quality of our care. In 36 patients with hepatocellular carcinoma treated with transcatheter arterial infusion and embolization, the arithmetic mean survival time after treatment was 412.1 days and time at home was 305.6 days. The rate of being at home doing survival time was 74.2% after the arterial infusion chemotherapy in 39 patients. The rate of being at home in 9 cases with one-shot infusion of Adriamycin was 43.5% (111 days); that in 9 cases with infusion of Mitomycin C microcapsules was 86.6% (716 days); that in 17 cases with transcatheter arterial embolization using spongel was 72.0% (234 days),; and that in 4 cases with infusion using implantable reservoir was 84.6% (220 days). In non-resected patients with chemotherapy, the rate of being at home was 20.3% for 61 cases of gastric cancer patients, 30.7% for 11 cases of colon cancer, 9.6% for 14 cases of gallbladder cancer and 39.8% for 112 cases of lung cancer. The arterial infusion and embolization of hepatocellular carcinoma has made it possible to lengthen the time that patients may stay home and thereby assure good quality of life.
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PMID:[Evaluation of quality of life in arterial infusion chemotherapy of hepatocellular carcinoma]. 216 36

Sixteen patients with metastatic carcinoma of the colon were treated with a regimen of leucovorin 200 mg/m2, given as a 10-min infusion followed by a median dose of 833 mg/m2 (range 500-1000 mg/m2) 5-fluorouracil every two weeks. For the 16 patients with proven metastatic disease, two-year survival exceeds 50%. Responses were: 2 complete; 4 partial; 4 minor; 3 progression; and 3 not evaluable but without progression to date. Toxicities include: 8 (50%) leukopenia; 9 (56%), 1 severe thrombocytopenia; 9 (56%), 2 severe, diarrhea; 9 (56%), 3 severe, nausea/vomiting; 8 (50%), 1 severe, stomatitis; 7 (44%) conjunctivitis; 6 (38%) alopecia; and 13 (81%), 3 severe, neurotoxicity. Leucovorin appears to exert a dose-dependent beneficial effect on both the response and survival produced by the intermittent high-dose 5-fluorouracil schedule. This benefit first appears to increase substantially when the leucovorin dose is increased from 120 to 200 mg/m2. Findings identify a testable candidate regimen for selected good risk patients. Full selection criteria remain to be identified.
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PMID:Dose-dependent leucovorin efficacy with an intermittent high-dose 5-fluorouracil schedule. 220 56


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