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)

The effectiveness and toxicity of antitumor drugs vary depending on dosing time associated with the 24-h rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. Such chronopharmacological phenomena are influenced by not only the pharmacokinetics but also pharmacodynamics of medications. For example, the antitumor effect and/or toxicity of irinotecan hydrochloride, interferon, and antiangiogenic agents vary depending on the dosing time associated with the 24-h rhythm of their target enzyme, receptor, protein, and pharmacokinetics. Many of them are controlled by clock genes. Chronotherapy is especially relevant when the risk and/or intensity of the symptoms of disease vary predictably over time. In a randomized multicenter trial involving patients with previously untreated metastases from colorectal cancer, the chronomodulated infusion of oxaliplatin, fluorouracil (5-FU), and folinic acid is compared with a constant-rate infusion method. Side effects such as stomatitis, peripheral sensory neuropathy are lower and the objective response is higher in the chronotherapy as compared with the fixed-rate infusion. The merit of chronomodulated infusion is supported by the 24-h rhythm of DNA synthesis and the activity of dehydropyrimidine dehydrogenase, which brings about the intracellular catabolism of 5-FU. Although interferon (IFN) also alters the clock function, the disruptive effect of IFN on clock function can be overcome by devising a dosing regimen that minimizes adverse drug effects on clock function. Thus one approach to increasing the efficiency of pharmacotherapy is the administration of drugs at times at which they are most effective and/or best tolerated.
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PMID:Circadian rhythms in the CNS and peripheral clock disorders: chronopharmacological findings on antitumor drugs. 1729 45

The platinum derivative oxaliplatin is widely used in colorectal cancer. Its side effects differ from those of the other platinum compounds cisplatin and carboplatin. An acute, painful hyperexcitability syndrome (HES) accompanied by cold induced paresthesia, dysesthesia and myotonia is unique to oxaliplatin, whereas a chronic, peripheral sensory neuropathy (PSN) can be caused by all platinum compounds. It is believed that HES is the result of peripheral nerve hyperexcitability as a consequence of voltage-gated sodium channel dysfunction, which may be caused by calcium level imbalance. Therapeutic options for HES are the administration of calcium and magnesium, the serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine and the thiophosphate amifostine.
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PMID:[Painful hyperexcitability syndrome with oxaliplatin containing chemotherapy. Clinical features, pathophysiology and therapeutic options]. 1757 4

We have been collecting data on the adverse reaction of FOLFOX 4 chemotherapy in our hospital from April 2005 to October retrospectively, by electronic clinical records. A retrospective study of 123 patients receiving FOLFOX 4 for advanced colorectal cancer was conducted. Survey results showed high incidences of hemotoxicity (52.8%), chronic sensory neuropathy (16.2%) and allergic reactions (15.4%). In the initial FOLFOX 4 therapy, appetite loss (60.1%), vomiting (19.5%) and acute sensory neuropathy (33.3%) were observed. We prepared a brochure in order to minimize inter-individual differences in pharmaceutical care and drug consultation by clinical pharmacists and to ensure the accurate understanding of patients. We feel sure that this kind of activity will help us to provide better pharmaceutical care for patients.
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PMID:[Drug information brochure for patients undergoing FOLFOX 4 chemotherapy based on survey of adverse reactions]. 1787 40

Epirubicin, cisplatin and continuous infusion of 5-FU is a widely used palliative regimen in patients with gastric cancer. If cisplatin is substituted by oxaliplatin and 5-FU by capecitabine this regimen can be administered in the outpatient setting. Dose-limiting toxicity of oxaliplatin is peripheral sensory neuropathy and it is recommended to give oxaliplatin as a 120 min infusion. However, in patients with colorectal cancer a 30 min infusion of oxaliplatin can safely be administered without increasing neurotoxicity, standard infusion time is 30 min at our departments. In our phase I study the recommended doses of EXE was established (Dupont et al, 2006). Patients with non-resectable gastric adenocarcinoma were eligible. Patients received EXE (epirubicin 50 mg m(-2) day 1; capecitabine 1000 mg m(-2) day(-1) continuously and oxaliplatin 130 mg m(-2) day 1) as outpatient therapy every third week for a maximum of 8 cycles. From June 2004 to September 2005, we enroled 54 patients. Median age was 60 years (31-74 years) Median number of courses was 6 (1-8). Response rate was 45%. Median PFS was 6.8 (5.2-7.9) months and median survival was 10.1 (7.9-1.1) months. Most important grade 3 toxicities were as follows: nausea, vomiting, and diarrhoea (6%). Neurotoxicity grade 2 was seen in 36.5%. We therefore conclude, that EXE every third week is a convenient regimen that easily can be administrated in the outpatient setting but the regimen needs further evaluation in a phase III study.
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PMID:Phase II study of short-time oxaliplatin, capecitabine and epirubicin (EXE) as first-line therapy in patients with non-resectable gastric cancer. 1923 27

In performing FOLFOX chemotherapy (infusional 5-FU/LV with oxaliplatin) for advanced colorectal cancer, the neurotoxicity of oxaliplatin (L-OHP) is the dose-limiting factor. A retrospective study of 25 consecutive patients, receiving modified FOLFOX6 (mFOLFOX6) for advanced colorectal cancer, was conducted. From March 2006 to February 2008, we investigated the process of development of sensory neuropathy by adverse effect grading and our original interview-based intake about the afflicted regions. Neurotoxicity developed in 21 cases (84%) after 6 courses and the cumulative L-OHP dose was 410 mg/m(2) in median. In 11 cases (52%), it developed from the fingers, while in 8 cases (38%), it occurred from the fingers and toes simultaneously. It developed from the toes or tongue only in one case each. In 6 cases (55%), in which it occurred from the fingers, the symptom aggravated to grade 2 (G2) according to the Neurotoxicity Criteria of DEBIOPHARM (DEBNTC). On the other hand, in cases of coexpression of the fingers and toes, 7 cases (88%) developed G2 neuropathy, among one of whom suffered from grade 3 (G3). The coexistence of diabetes mellitus without neuropathy had no influence on the development of the neurotoxicity in the grading of DEB-NTC. One month after the last mFOLFOX6 therapy, neurotoxicity newly developed in one case, and was aggravated in two cases two months after cessation of the chemotherapy. Therefore, careful observation of the course should be continued even after the end of mFOLFOX6 therapy. Our results suggest that L-OHP neurotoxicity develops on fingers or fingers and toes simultaneously in most cases. And when it occurred on fingers and toes simultaneously, it would aggravate to G2 or G3 during the chemotherapy. The interviewed-based intake about the afflicted region, such as ours, can be used to predict the deterioration of the neurotoxicity.
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PMID:[Survey of oxaliplatin-associated peripheral sensory neuropathy using an interview-based questionnaire in patients with advanced colorectal cancer]. 1969 71

With advances in treatment, colorectal cancer (CRC) is being transformed from a deadly disease into an illness that is increasingly curable. With this transformation has come increased interest in the unique problems, risks, needs, and concerns of survivors who have completed treatment and are cancer-free. Research has shown that physical and mental quality of life for CRC survivors was inferior compared with age-matched individuals without cancer. Although issues and symptoms were most prominent during the first 3 years, long-term effects of treatment can persist and include fatigue, sleep difficulty, fear of recurrence, anxiety, depression, negative body image, sensory neuropathy, gastrointestinal problems, urinary incontinence, and sexual dysfunction. The unique challenges and issues of CRC survivors can and should be addressed by health care providers and the research community to ensure effective interventions and models of care to manage these problems. This article discusses what is known about the long-term effects of CRC treatment on quality of life, the care of survivors, and existing models of survivorship care.
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PMID:The challenges of colorectal cancer survivorship. 1975 48

Oxaliplatin has become an integral part of the standard treatment for advanced colorectal cancer. While oxaliplatin has only mild hematologic and gastrointestinal side effects, its dose-limiting toxicity is a cumulative sensory neurotoxicity. Oxaliplatin causes a unique, but frequent, acute sensory neuropathy that is triggered or aggravated by exposure to cold but is rapidly reversible, without persistent impairment of sensory function. Various strategies have been proposed to prevent or treat oxaliplatin-induced neurotoxicity. One such strategy is the "Stop-and-Go" concept, which uses the reversibility of neurologic symptoms to aim at delivering higher cumulative oxaliplatin doses, as long as the therapy is still effective and the other is the administration of neuromodulatory agents (ie, calcium-magnesium infusions, carbamazepine, gabapentin, amifostine, alpha-lipoic acid, and glutathione) that could limit the neurotoxic effects of oxaliplatin. Among all of the agents, intravenous calcium and magnesium have shown the most promise in prophylaxis and treatment of oxaliplatin-induced neurotoxicity. We report a case of a patient, in which oral calcium supplements not only were successful in treating his neurotoxicity, but we also were able to administer a cumulative dose of 2500 mg/m(2) (990 mg/m(2) with oral calcium). Although the current recommendations for the management of the acute and cumulative neurotoxicity from oxaliplatin with the use of infusion of Ca/Mg remain valid, our case is the first report demonstrating the role of oral minerals in ameliorating neurotoxicity from oxaliplatin. Future studies to evaluate the role of oral Ca/Mg are warranted, since they could prove to be an effective, less expensive and more convenient way to treat and prevent oxaliplatin-associated toxicity.
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PMID:Oral Calcium Ameliorating Oxaliplatin-Induced Peripheral Neuropathy. 1981 92

We retrospectively investigated the frequency and severity of adverse events in 124 patients with colorectal cancer who were treated by mFOLFOX6 regimen from August, 2005 to December, 2006. The incidences of grade 3/4 adverse events were; leucopenia 16%, neutropenia 40%, anemia 11%, thrombocytopenia 7%, febrile neutropenia 7%, nausea 3%, vomiting 2%, anorexia 2%, diarrhea 4%, fatigue 7%, and alopecia 0%. The incidences of all grades and grade 3/4 hypersensitivity reaction were 35% and 4%, and the median number of course when it firstly appeared was 6(range, 1-21). The incidences of all grade and grade 3 peripheral sensory neuropathy were 74% and 6%, and the median number of course when it firstly appeared 11(range, 6-16). The incidences of adverse events in this cohort were similar or lower than those reported in Western countries. Our investigation shows that mFOLFOX6 regimen is tolerable in clinical practice in Japan. The informed consent form was revised based on these results. The incidences of adverse events were renewed to provide useful information and improve self-care ability. The symptoms and the time to appearance of the hypersensitivity reaction and peripheral sensory neuropathy were added. We think it is important to provide the information based on the clinical practice.
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PMID:[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen]. 1983 30

Oxaliplatin, a third generation of platinum-based anti-neoplastic agent has been approved for colorectal cancer in both adjuvant and metastatic settings. In addition, oxaliplatin is also indicated for other gastrointestinal malignancies such as metastatic pancreatic cancer in combination with gemcitabine. Its common toxicities include infusional hypersensitivity reaction (HSR), GI symptoms with anorexia/nausea/vomiting, sensory neuropathy and bone marrow suppression. We report a case with persistent dry cough as a variant HSR to oxaliplatin. The patient is a 75-year-old gentleman with gemcitabine refractory metastatic pancreatic cancer who received oxaliplatin and mitomycin C for palliation. He developed sudden onset dry cough without infectious etiology during the 4th infusion of oxaliplatin. Robitussin with codeine and antibiotics did not offer any relief and the cough terminated after cessation of oxaliplatin for two weeks. We believe this to be the first case in the literature with cough as a sole manifestation of HSR to oxaliplatin.
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PMID:Variant hypersensitivity reaction (HSR) presented with persistent dry cough after receiving oxaliplatin in a pancreatic cancer patient. 2012 9

Thirty-seven patients with advanced or recurrent colorectal cancer were treated with mFOLFOX6 or mFOLFOX6 with a Bevacizumab regimen between September 2008 and March 2009. Then, we evaluated persistent neuropathy using the National Cancer Institute Common Terminology Criteria for Adverse Events (ver. 3). As a result of the research, grade 1-3 sensory neuropathy was observed in 5.6% after 3 cycles, 44. 4% after 5 cycles, 83. 3% after 8 cycles, and 83. 4% after 10 cycles. The average dose of L-OHP (mg/m2) until persistent sensory neuropathy appeared was grade 1: 399.7+/-157. 0 (17/ 37 patients); grade 2: 418.0+/-214. 1 (5/37 patients); and grade 3: 498.0+/-152. 8 (3/37 patients). As has been shown in international clinical trials, the severity and frequency of L-OHP-induced neurotoxicity are associated with the cumulative dose and duration of L-OHP administration. Further research is necessary to develop strategies for preventing or treating this side effect.
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PMID:[Analysis of a case of oxaliplatin - induced persistence sensory neuropathy]. 2033 3


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