Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large number of reports have been devoted to the physiologic and toxic effects of methyl chloride, many of which are based on case histories involving occupational exposure. The detrimental actions of methyl chloride on the central and peripheral nervous systems are well established effects. It is a moderately severe narcotic and potentially severe nerve poison. Chronic intoxication is associated with damage to the central nervous system (CNS), kidneys, liver, bone marrow, cardiovascular system, respiratory system, and intestinal tract. The signs and symptoms range from the more severe medical dysfunctions such as cardiac irregularities, respiratory paralysis, nerve degeneration, and severe convulsions to the more subtle clinical observations such as CNS depression, nervousness and emotional instability, insomnia and anorexia, ataxia, blurred vision, light-headedness, nausea, dizziness, narcosis, and disorientation. The behavioral correlates of these and other neurotoxic effects of methyl chloride suggest that a gradual behavioral degradation occurs. Pharmacodynamic studies have shown the compound to be rapidly absorbed by the blood with most authors attributing the toxicity to an enzyme-catalyzed methylation reaction in the body. Despite the fact that several investigators have attempted to correlate such biological responses of methyl chloride with its toxicity, the present knowledge of the problem still lacks a detailed mechanism of action. Until such mechanisms are verified, adequate methods to assess subclinical neurological and behavioral changes must be effectively developed.
CRC Crit Rev Toxicol 1979 Nov
PMID:Behavioral, neurological, and toxic effects of methyl chloride: a review of the literature. 38 67

Carbetimer (carboxyimamidate) was administered at a dose of 6,500 mg/m2/day intravenously for 5 consecutive days to 14 patients with measurable metastatic or recurrent colorectal cancer in a single institution phase II study of the Northern California Oncology Group. A total of 38 cycles of therapy were administered; nine patients completed at least three cycles of treatment. No partial or complete responses were observed. One patient did have a greater than 50% response in the liver while developing new retroperitoneal lymphadenopathy and is considered a nonresponder. Carbetimer was well tolerated with elevations of calcium from 10.2 to 12.5 mg/dl in nine patients, prolongation of prothrombin time and partial thromboplastin time in 14 patients, proteinuria in 10 patients, dizziness in six patients, nausea in two patients, and venous pain during infusion in three patients. Myelosuppression was not observed. Carbetimer at this dose and schedule is inactive in the treatment of colorectal cancer.
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PMID:A phase II trial of carbetimer for the treatment of colorectal cancer. A trial of the Northern California Oncology Group. 219 95

Preclinical data showed that the cytotoxic effects of 5-fluorouracil (5-FU) are augmented by interferon (IFN). In a small study, 13 of 17 patients with advanced colorectal cancer responded to a regimen of 5-FU with IFN. Using the same dose and schedule as in this pilot study, 38 previously untreated patients with metastatic colorectal carcinoma were treated with continuous intravenous (IV) infusion of 5-FU 750 mg/m2 daily for 5 days, followed by weekly bolus 5-FU at 750 mg/m2 and subcutaneous IFN at 9 million units three times per week. Of 35 evaluable patients, nine (26%) had a partial response (95% confidence limit, 11% to 41%), with a median response duration of 7.5 months (range, 4.4 to greater than 11.7 months). Seven patients (20%) had a minor response, and ten (28%) had stable disease. The most common toxicities observed were stomatitis (52%) and diarrhea (43%). Neurotoxicity was seen in 34% of patients and consisted of gait disturbance, dizziness, confusion, memory loss, and dementia. Because of toxicity, 84% of patients required a reduction of the IFN dose by at least 50%, and 63% required reduction of the 5-FU dose by at least 25%. Although the combination of 5-FU and IFN in patients with advanced colorectal carcinoma has some activity, the regimen was toxic, and the observed response rate (26%) was not substantially superior to alternative 5-FU programs.
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PMID:Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma. Assessment of activity and toxicity. 224 87

In the community of Kungsbacka, Sweden, with about 48,000 inhabitants, all subjects with colorectal cancer were studied during a three-year period. The incidence was 30 per 100,000 inhabitants per year. In all there were 42 cases. Blood in the stools, anaemia, tiredness, and dizziness were common initial signs and symptoms. Diarrhoea and constipation were also rather frequent. Positive test for faecal occult blood was observed in 40%, negative tests in 12% while in 48% no such test had been performed. The majority of the subjects (64%) first visited a general practitioner (GP). Mean doctor's delay was five months. More than half the cancers were located in the rectal or sigmoid area. Subjects in whom no metastases were observed had a favourable prognosis, compared with those with distant metastases. Since most patients with colorectal cancer first visit a GP for their symptoms, the GP has an important role in the diagnosis of colorectal cancer.
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PMID:The diagnosis of colorectal cancer--experiences from the community of Kungsbacka, Sweden. 235 72

A Phase II study of a new fluorinated pyrimidine (TAC-278) was performed in 14 institutions from May 1980 to April 1981. 400-1200 mg of TAC-278 was orally administered in 2 to 4 divided doses every day for more than 4 weeks. Selection of patients and evaluation of clinical response were done according to the criteria for "Evaluation of Clinical Effects of Chemotherapy on Solid Tumors" by Koyama and Saito. A total of 188 patients were entered in the study and 96 of them were evaluable. Partial responses were observed in 9.4% (9/96) of the evaluated cases. Stomach cancer and colorectal cancer showed partial responses in 10.8% (4/37) and 20% (5/25), respectively. As for side effects, slight gastrointestinal symptoms (loss of appetite, nausea and vomiting etc.) were found in 24% and CNS-symptoms such as dizziness and disorientation were observed in approximately 8% of the patients.
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PMID:[Phase II study of a new fluorinated pyrimidine, ethyl (+/-)-t-6-butoxy-5-fluoro-2, 4-dioxohexahydropyrimidine-r-5-carboxylate (TAC-278)]. 718 76

3,5-Dichloro-2,4-dimethoxy-6-(trichloromethyl)pyridine (penclomedine, NSC 338720, CRC 88-04) is an alpha-picoline derivative with anti-tumour activity in preclinical models. Penclomedine administration by 1-h intravenous infusion on 5 consecutive days was repeated 3 weekly in the absence of dose-limiting toxicity (DLT) or disease progression. Five dose levels were investigated (22.5-340 mg m(-2) day[-1]). Eight men and eight women were entered, median age 59 years (range 39-73 years), with good performance status (ECOG 0/1) in 11 patients. A total of 13 out of 16 patients had received previous chemotherapy. Common toxicity criteria grade (CTCg) II vomiting was recorded at all dose levels. Neurotoxicity (cerebellar ataxia and dizziness) was the DLT, CTCg III toxicity occurring in three out of three patients treated at 340 mg m(-2) day(-1). CTCg III dizziness was noted in one out of three patients at 250 mg m(-2) day(-1). Neurotoxicity developed during the 1-h infusion and persisted for a variable period (maximum 5 h) after infusion. Prophylactic antiemetic drugs appeared to reduce associated vomiting but did not prevent ataxia. No antiproliferative toxicities were noted and no anti-tumour responses were documented. Penclomedine pharmacokinetic studies confirmed preclinical evidence of extensive apparent distribution (93 l m[-2]) and rapid clearance (41 l h[-1] m[-2]). Purkinje cell loss has been identified in preclinical models after intraperitoneal administration (O'Reilly et al, 1996a) and further clinical development of penclomedine will focus on oral administration.
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PMID:Dose-limiting neurotoxicity in a phase I study of penclomedine (NSC 388720, CRC 88-04), a synthetic alpha-picoline derivative, administered intravenously. 951 62

Stereotactic radiosurgery (SR) is being used with increasing frequency in the treatment of brain metastases. This study provides data from a clinical experience with radiosurgery in the treatment of cases with multiple metastases and identifies parameters that may be useful in the proper selection and therapy of these patients. From January 1993 to April 1997, 97 patients (43 women and 54 men; median age 58 years) suffering from multiple brain metastases (median 3; range 2-4) in MRI scans, received SR with the Gamma Knife. The median dose at the tumor margin was 20 Gy (range 17-30 Gy). Median tumor volume was 3900 cmm (range 100-10,000). Different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness and ataxia had been the predominant neurological symptoms. Major histologies included lung carcinoma (44%), breast cancer (21%), renal cell carcinoma (10%), colorectal cancer (8%), and melanoma (7%). The median survival time was 6 months after SR. The actual one-year survival rate was 26%. In univariate and multivariate analysis, a higher Karnofsky performance rating and absence of extracranial metastases had a significantly positive effect on survival. Local tumor control was achieved in 94% of the patients. Complications included the onset of peritumoral edema (n = 5) and necrosis (n = 1). SR induces a significant tumor remission accompanied by neurological improvement and, therefore, provides the opportunity for prolonged high quality survival. We conclude that radiosurgical treatment of multiple brain metastases leads to an equivalent rate of survival when compared to the historic experience of patients treated with whole brain radiotherapy. Patients presenting initially with a higher Karnofsky performance rating and without extracranial metastases had a median survival time of nine months. Each such case should therefore be evaluated based on these factors to determine an optimal treatment regimen.
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PMID:Prognostic factor analysis for multiple brain metastases after gamma knife radiosurgery: results in 97 patients. 1042 Oct 75

The reported incidence of hypersensitivity reactions (HSRs) associated with oxaliplatin in patients with colorectal cancer (CRC) is approximately 12%, with 1 - 2% of patients developing grade 3 or 4 in severity. However, the recent rising incidence of HSR to oxaliplatin observed is the result of increasing clinical use. HSR to oxaliplatin may manifest as facial flushing, rash/hives, tachycardia, dyspnoea, erythema, pruritus, fever, tongue swelling, headache, chills, weakness, vomiting, burning sensations, dizziness and oedema. Anaphylactic shock is rare but serious, and must be considered in the event of hypotension. No definitive approaches to prevent and treat HSR associated with oxaliplatin are available; however, few successful strategies have been reported. Such strategies include: slowing the infusion rate, use of steroids and antagonists of type 1 and 2 histamine receptors, and desensitisation. Successful implementation of oxaliplatin desensitisation protocols based on other platinum-containing compounds have been reported, which could enable a small number of patients who experience severe HSR to further receive an effective therapy for CRC. However, reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitisation strategies are still missing. Recently, subcutaneous adrenaline has also been utilised as an alternative approach to manage HSR to oxaliplatin. Knowledge of this rare but real toxicity of oxaliplatin is paramount because the use of this drug continues to increase not only for the treatment of patients with stage II-IV CRC, but also other solid malignancies. In this article, the author discusses the incidence, clinical presentation, pathogenesis, risk factors and current strategies of management of HSR associated with oxaliplatin.
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PMID:Hypersensitivity reactions associated with oxaliplatin. 1690 58

Hypersensitivity reactions (HSR) to oxaliplatin in patients with colorectal cancer include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. We report a patient with fever as the sole manifestation of initial HSR, review the literature and discuss the management of HSR. A 57-year-old female with T3N2M0 rectal adenocarcinoma received modified FOLFOX-6. She tolerated the first 8 cycles without any toxicities except grade 1 peripheral neuropathy and nausea. During 9th and 10th infusions, she developed fever to a maximum of 38.3 centigrade with stable hemodynamic status despite medications. During 11th infusion, she developed grade 3 HSR consisting of symptomatic bronchospasm, hypotension, nausea, vomiting, cough, and fever. On examination, she was pale, cyanotic, with a temperature of 38.8 centigrade, BP dropped to 95/43 mm Hg, pulse of 116/min and O(2) saturation of 88%-91%. She was hospitalized for management and recovered in 24 h. Fever alone is not a usual symptom of oxaliplatin HSR. It may be indicative that the patient may develop serious reactions subsequently, as did our patient who developed hypotension with the third challenge. Treatment and prevention consists of slowing the infusion rate, use of steroids and antagonists of Type 1 and 2 histamine receptor antagonists, whereas desensitization could help to provide the small number of patients who experience severe HSR with the ability to further receive an effective therapy for their colorectal cancer.
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PMID:Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction. 1787 1

Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States.
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PMID:Hypersensitivity reactions to oxaliplatin and other antineoplastic agents. 1837 76


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