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)

Based on in vitro studies that have demonstrated synergy between recombinant alfa-2a-interferon (rIFN alpha-2a) and the fluoropyrimidine, fluorouracil (5FU), against two human colon cancer cell lines, a pilot clinical trial was initiated to determine the effects of the combination of 5FU and rIFN alpha-2a in patients with advanced, unresectable colorectal carcinoma. A total of 30 patients were enrolled; all were evaluable. 5FU was administered as a loading course, 750 mg/m2 daily for 5 days by continuous infusion followed by weekly bolus therapy, rIFN alpha-2a, 9 MU, was administered subcutaneously three times per week. Of 17 previously untreated patients evaluable for response, 13 achieved a response. Three patients had disease progression. No previously treated patients had a major response. There was one death clearly related to therapy, an event preceded by watery diarrhea and neutropenic sepsis. Other toxicities were reversible and responded to dose reduction. With a median follow-up of 16+ months, median survival has not been reached among the previously untreated patient cohort. We conclude that the combination of 5FU and rIFN alpha-2a is an active regimen against disseminated colorectal cancer in previously untreated patients.
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PMID:Fluorouracil and recombinant alfa-2a-interferon: an active regimen against advanced colorectal carcinoma. 258 16

Many patients who present with acute or chronic diarrhea do not have an important organic disease. Most have functional diarrhea. The history, clinical examination, and initial laboratory studies should lead to a provisional diagnosis with respect to organic or functional origin and help define whether the disease affects the small or large intestine. Specific studies are then obtained to define organic causes. The most common causes of acute diarrhea are infections and drugs, while the most common causes of chronic diarrhea are inflammatory bowel disease, malabsorption, parasitic infections, carcinoma of the large bowel, and metabolic diseases. Clinicians should remember that patients with functional diarrhea are as prone to other severe disease as the rest of the population and avoid allowing the functional problem to mask other signs.
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PMID:Diagnosis and therapy of acute and chronic diarrhea. 231 56

Disease-oriented phase II trials of doxifluridine were performed in advanced colorectal, breast, renal, endometrial, stomach, and ovarian carcinomas. The dose schedule recommended by the phase I trial (12.5 g/m2 by continuous iv infusion over 6 hours once a week for 3 weeks followed by a 1-week rest) was chosen first: the initial dose was later decreased to 10 g/m2 due to the fact that several neurotoxic effects were reported. A total of 207 patients were entered: 137 patients who received at least two courses of treatment were evaluable for response. Therapeutic activity was demonstrated in breast cancer [two complete responses (CR) and 13 partial responses (PR) among 42 patients], colon cancer (seven PRs among 35 patients), and rectal cancer (six PRs among 23 patients). Some therapeutic activity was detected in ovarian cancer (one CR among nine patients), endometrial cancer (one PR among five patients), and stomach cancer (one PR among five patients). No significant activity was noticed in renal cancer (one PR among 18 patients). Nonhematological toxicity was evaluated according to World Health Organization criteria. Nausea and vomiting were recorded in 50% of the patients (Grade 3-4 in 5%), diarrhea was recorded in 20% (Grade 3-4 in 5%), and cutaneous and allergic reactions were recorded in 10% (Grade 3-4 in 2%). Myelotoxicity during the first treatment course was mild; median wbc and platelet count nadirs (x 10(9) cells/L) were 4.1 (range, 0.1-11) and 194 (range, 20-482), respectively. Nevertheless, some cases of acute leukopenia and thrombopenia were reported. Consciousness alterations and neurologic symptoms were the major side effects (72 of 173 evaluable patients), since treatment had to be interrupted in 34 patients and four lethal neurotoxic effects occurred. At the same total dose of doxifluridine, the risk of neurotoxicity significantly increases with age and with the weekly dose and to the contrary it decreases with increasing bilirubin level. Although activity was demonstrated, this treatment cannot be recommended because of major neurotoxicity. Further pharmacological studies seem warranted to define the optimal dosage schedule and to obtain a better therapeutic index.
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PMID:Phase II clinical evaluation of doxifluridine. 294 45

Iproplatin was administered intravenously over 30 min daily for 5 consecutive days every 3 weeks to 80 evaluable patients with a variety of refractory solid tumor malignancies. Thrombocytopenia was the dose-limiting toxicity. Reversible drug-induced renal dysfunction was observed in 3 patients. One patient sustained mild ototoxicity but neurotoxicity was not encountered. Transient neutropenia, anemia, nausea, vomiting, diarrhea, elevations of liver enzymes, alopecia, and skin rash also occurred. The spectrum and severity of toxicity of iproplatin were found to differ from those of cisplatin. The maximally tolerated dose (MTD) was 45 mg/m2/day in patients who received prior chemotherapy and 65 mg/m2/day in those who did not. No complete responses occurred. Partial responses were obtained in 2/15 patients with colon cancer, 3/18 with breast cancer, 2/4 with carcinoma of unknown primary site and 1/2 with pancreatic cancer. Thirteen patients with lung (5), breast (4), colon (2), head and neck (1) and cervical (1) cancers had stable disease. Based on the different toxicity profiles between iproplatin and cisplatin and the possible antitumor efficacy of the former, phase II investigation of iproplatin has been initiated.
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PMID:Phase I--preliminary phase II trial of iproplatin, a cisplatin analogue. 319 85

We determined the therapeutic effect of fluorouracil (5-FU) in combination with folinic acid (FA) in patients with measurable recurrent or metastatic carcinoma of the colon or rectum by comparing it to standard 5-FU therapy in a prospective randomized controlled trial. Patients were randomized to receive either FA, 200 mg/m2/d for five consecutive days, or nothing. All patients received 5-FU, 370 mg/m2/d for five days on the first course, with subsequent dose modifications to maintain equal toxicity in the two arms. One hundred thirty patients were entered on trial and only five were excluded from the analysis because they did not meet the eligibility criteria or they refused therapy after randomization. The two treatment arms were balanced for 11 clinical characteristics. Patients were evaluated for response at the end of every two treatment courses and toxicity after every course of therapy. Median follow-up was 1.45 years. Dose-limiting toxicity was mucositis and diarrhea on this treatment schedule, although neutropenia was apparent. The response rate was 33% (21 of 63 patients) in the 5-FU and FA arm and was 7% (four of 61 patients) in the 5-FU arm (P less than .0005). Time to disease progression was significantly different in the combination arm as compared with the single-agent arm (P = .023). Overall survival was significantly longer for patients treated with 5-FU and FA as compared with those receiving 5-FU alone (P = .05). The median survival was 12.6 months for patients receiving the combination, and 9.6 months for those receiving 5-FU alone. Our results indicate that the combination of 5-FU and FA is effective treatment for patients with metastatic or recurrent carcinoma of the rectum and colon who have not received prior chemotherapy.
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PMID:A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. 328 Jul 41

The therapeutic activity of 5-FU in large bowel cancer is enhanced by increasing the intracellular pool of reduced folates. We treated 45 patients with advanced colon cancer with HDFA and 5-FU for 5 consecutive days. None had been given previous radio- or chemotherapy. All had measurable disease. Not one complete response was observed. Thirteen of the 39 evaluable patients showed partial response. Median duration of response was 9+ months. The probability of 50% survival was 15 months for all evaluable patients. There was no case of severe toxicity and the principal toxic effects were oral mucositis and diarrhea. To date, HDFA + 5-FU is one of the most effective treatments for large bowel cancer.
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PMID:High-dose folinic acid (HDFA) combined with 5-fluorouracil (5-FU) in first line chemotherapy of advanced large bowel cancer. 350 48

Colon carcinoma, the second leading cause of cancer-related deaths in the United States, is resistant to chemotherapy in a large majority of cases. Single-agent and combination chemotherapy have failed to prolong survival. New approaches are clearly needed. In experimental models, a steep dose-response curve for colorectal cancer has been demonstrated using various agents. The hematopoietic toxicity of high-dose therapy with these drugs can be circumvented by autologous bone marrow transplantation. We investigated the use of high-dose melphalan with autologous bone marrow rescue in 20 patients with metastatic colon carcinoma. Each patient received melphalan, 180 mg/m2 intravenously (IV), followed eight hours later by bone marrow infusion. Median duration of granulocytopenia (less than 500 neutrophils/microL) was twelve days (range, 5 to 35 days), while transfusion-dependent thrombocytopenia (less than 20,000 platelets/microL) had a median duration of eight days (range, 3 to 23 days). Time to bone marrow engraftment was not affected by prior 5-fluorouracil therapy. Nausea and vomiting occurred in 14 patients but was generally short lived. Mild stomatitis, esophagitis, and diarrhea were common. Severe gastrointestinal (GI) side effects did not occur. One treatment-related death occurred secondary to intramural tumor necrosis, which resulted in massive lower GI bleeding. Complete responses were observed in three patients (15%) and partial responses in six patients (30%), for an overall response rate of 45%. Median survival was 198 days in this group of patients with extensive disease. High-dose melphalan therapy for metastatic colon carcinoma, when used with autologous bone marrow transplantation, appears to achieve a high response rate with tolerable toxicity. Further investigation is needed to define the role of this therapy in the care of advanced colon carcinoma.
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PMID:Phase II trial of high-dose melphalan and autologous bone marrow transplantation for metastatic colon carcinoma. 353 54

Fulminant, necrotizing colitis is a frequent, and generally fatal, complication of severe granulocytopenia, occurring during the treatment of hematological malignancies. In these cases, the patient complains of severe peritonitis, including nausea, vomiting, abdominal pain, diarrhea or melena, and a high temperature. Here, a rare case of anticancer chemotherapy-induced diffuse necrotizing enterocolitis throughout the entire intestinal tract is presented, which developed in a patient who did not have a hematologic malignancy but who had colon cancer, the only clinical symptom of which was watery stools, without any evidence of peritoneal irritation. Full attention should be paid to progressive diarrhea in patients with malignancies during anticancer chemotherapy.
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PMID:Induction of diffuse necrotizing enterocolitis by anticancer chemotherapy. 362 12

The Eastern Cooperative Oncology Group (ECOG) studied 29 patients with advanced measurable colon cancer who were treated with Aminothiadiazole (NSC #4728) 125 mg/m2 intravenously. Allopurinol 300 mg daily was taken by all patients during treatment. Three patients (12%) demonstrated partial responses on this regimen. Hematologic toxicity did not occur. Gastrointestinal toxicity was severe in 16% of patients and consisted primarily of vomiting and diarrhea. No life-threatening toxicity was encountered. A lack of appreciable toxicity together with the few responses seen suggest that further studies at higher dose may be indicated.
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PMID:Aminothiadiazole (NSC #4728) in patients with advanced colon cancer. A phase II study of the Eastern Cooperative Oncology Group. 366 89

Vibrio vulnificus, a marine Vibrio associated with severe extraintestinal infections, has not been previously implicated as a cause of infectious diarrhea. Three patients were identified with diarrheal illness from whom this organism was the sole pathogen recovered from cultured stool specimens. All three had eaten raw oysters within one week of becoming ill. These patients were all taking medication that reduces gastric acidity, two were heavy drinkers of alcohol, and one had unrecognized colon cancer; these factors may have predisposed to the development of disease. Clinicians should consider that V. vulnificus may be a cause of gastroenteritis in patients who have consumed raw oysters.
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PMID:Gastroenteritis in patients with stool isolates of Vibrio vulnificus. 394 53


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