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 clinical study has been conducted to investigate whether chemotherapy with 24 hour infusion of CPT-11/oral UFT/LV is an effective and safe regimen for advanced or recurrent colorectal cancer. The chemotherapy consisted of a fixed dose of UFT (300 mg/m(2)/day)/LV (75 mg/body) orally administered daily (day 1-day 21) followed by CPT-11 (80-120 mg/m(2)) iv, as a 24-hour infusion (day 1 and day 15). This treatment was carried out weekly for 3 weeks followed by a week rest period, then repeated every 4 weeks. The MTD was reached at 120 mg/m(2) of CPT-11 (2 cases of grade 3 leucopenia and neutropenia) and 100 mg/m(2) (a case of grade 3 anorexia). Therefore the 100 mg/m(2) dose level was established as the recommended dose (RD). All patients were evaluable for efficacy; 5 PR, 4 SD and 1 PD. The overall response rate was 41.7%. The present study suggests that combination chemotherapy with CPT-11 and oral UFT/LV is well tolerated and might be a promising regimen for advanced or recurrent colorectal cancer.
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PMID:[24 hour infusion of CPT-11/oral UFT/LV]. 1683 76

Oxaliplatin (L-OHP) has been established as a key drug for advanced colorectal cancer, and combination therapy with 5-FU/Leucovorin (LV)(FOLFOX regimen) is commonly used in Europe and the US. A phase I study of modified (m) FOLFOX 6 therapy was conducted to determine the recommended dose (RD) of 5-FU infused for 46 hours. Inclusion criteria were unresectable advanced colorectal cancer,measurable lesions, performance status (PS; ECOG) 0-2, age 20-75 years, and adequate organ functions. L-OHP and l-LV was administered over 2 hours and followed by bolus injection and continuous infusion of 5-FU for 46 hours every 2 weeks. Two cycles of mFOLFOX 6 therapy were performed. Doses of L-OHP, l-LV, and bolus injection of 5-FU were fixed at 85 mg/m(2), 200 mg/m(2), and 400 mg/m(2), respectively. The dose of continuous infused 5-FU was escalated from 1,600 mg/m(2), (level 1), 2,000 mg/m(2), (level 2), 2,400 mg/m(2), (level 3), and 2,800 mg/m(2), (level 4). RD was determined in a dose escalation manner, and safety was evaluated according to NCI-CTC Ver 2.0. A total of 13 patients were enrolled. Male/female=7/6, PS 0/1/2=2/4/7, mean age 64 years (range 55-75). Thrombocytopenia was not observed, and grade 2 of neutropenia and peripheral neuropathy was observed in 4 and 6 out of 13 patients. No dose-limiting toxicity (DLT) was observed at level 1 (n=3), 2 (n=4), and 3 (n=4), but at level 4 (n=2), 2 patients experienced DLT; grade 3 easy fatigue and anorexia required treatment delay over 7 days. Level 3 was therefore determined as RD. A phase II study is ongoing to evaluate the efficacy of mFOLFOX 6 therapy.
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PMID:[A phase I study of modified FOLFOX 6 therapy for advanced colorectal cancer]. 1730 27

We evaluated the efficacy and safety of modified FOLFIRI for patients with refractory advanced or recurrent colorectal cancer. Modified FOLFIRI was given 29 patients (21 men and 8 women, with a median age of 61.0 years) from 2 to 16 times (median 10.0). 19 out of 29 patients were colon cancer, and the other 10 were rectal cancer. 18 patients were administered as first-line chemotherapy, and 11 were more than second line. CPT-11 was administered at a dose of under 150 mg/m(2), to remain within the limits in Japan. The response to treatment was CR in 3 patients, PR in 8, and SD in 12. The response rate was 37.9%. Grade 4 hematologic toxicities included leukocytopenia in 2 patients, neutropenia in 7 and anemia in 1. Grade 3/4 non-hematologic toxicities included febrile neutropenia in 4 patients, anorexia in 3, fatigue in 3, and nausea, diarrhea and interstitial pneumonia in 1. Except in 2 patients, all reactions could be controlled with the use of G-CSF or by setting drug holiday. In summary, modified FOLFIRI is a safe and effective regimen even at a dose of under 150 mg/m(2), of CPT-11. It can be given with good tolerance for patients with refractory advanced or recurrent colorectal cancer on an outpatient basis with due care especially for neutropenia.
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PMID:[Feasibility of modified FOLFIRI regimen for patients with refractory advanced or recurrent colorectal cancer]. 1730 28

Recent studies in chronobiology and the neurosciences have led to rapid growth in our understanding of the molecular biology of the human timekeeping apparatus and the neuroanatomic sites involved in signaling between the "master clock" in the hypothalamus and other parts of the brain. The circadian axis comprises a central clock mechanism and a downstream network of hypothalamic relay stations that modulate arousal, feeding, and sleeping behavior. Communication between the clock and these hypothalamic signaling centers is mediated, in part, by diffusible substances that include ligands of the epidermal growth factor receptor (EGFR). Preclinical studies reveal that EGFR ligands such as transforming growth factor-alpha (TGF-alpha) inhibit hypothalamic signaling of rhythmic behavior; clinical observations show that elevated levels of TGF-alpha are associated with fatigue, flattened circadian rhythms, and loss of appetite in patients with metastatic colorectal cancer. These data support the hypothesis that a symptom cluster of fatigue, appetite loss, and sleep disruption commonly seen in cancer patients may be related to EGFR ligands, released either by the cancer itself or by the host in response to the stress of cancer, and suggest that further examination of their role in the production of symptom clustering is warranted.
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PMID:Symptom clusters in cancer patients and their relation to EGFR ligand modulation of the circadian axis. 1750 May 4

A 74-year-old woman was referred to our hospital with complaints of constipation and abdominal distention caused by a sigmoid colon tumor. After examination, she was diagnosed as sigmoid colon cancer with multiple liver metastases. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative days 15, S-1 was started, and she was discharged on postoperative day 26. Each course consisted of daily oral administration S-1 for 4 weeks followed by 2 drug-free weeks. However, because of grade 2 anorexia in the 1st course, the treatment plan was changed to administration for 2 weeks and withdrawal for 1 week. After 7 courses of treatment, computed tomography revealed that the liver metastases were remarkably reduced. Although she experienced an adverse event involving a cutaneous symptom of grade 2, the treatment was continued under ambulatory management. After eight courses, elevation of tumor marker and metastasis at the right femur were found, and she died of the cancer 12 months after the operation. S-1 is expected to be an effective agent for the treatment of advanced colorectal cancer.
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PMID:[A case of sigmoid colon cancer with multiple liver metastases responding to S-1]. 1828 73

A sixty-year-old man was admitted with anorexia and abdominal mass. Colonoscopy revealed type 2 tumor at sigmoid colon. Computed tomography (CT) demonstrated multiple liver metastases. The patient was diagnosed as sigmoid colon cancer with multiple liver metastases. The patient was treated with mFOLFOX6 as neoadjuvant chemotherapy because the liver metastases were unresectable. However, after 2 cycles of mFOLFOX6, the level of CEA and CA19-9 much increased. The regimen was replaced by FOLFIRI. The level of CEA and CA19-9 decreased after 2 cycles of FOLFIRI. CEA and CA19-9 further decreased and colonoscopy and CT revealed a partial response after 5 cycles of FOLFIRI. The patient was subjected to curative resection. Sigmoidectomy and liver resection were performed. Histological response was Grade 1b at liver metastasis. The patient was discharged and had an uneventful recovery. Six months after surgery, CEA and CA19-9 decreased to normal level, and the patient is free of recurrence. Neoadjuvant chemotherapy for metastatic colorectal cancer may render some unresectable patients resectable, affording these patients the possibility of prolonged survival. However, the optimal approach is unknown.
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PMID:[A successfully resected case of colorectal cancer with multiple liver metastases treated with FOLFIRI after failure of mFOLFOX6]. 1834 6

Vorinostat (Zolinza) is a histone deacetylase inhibitor that has demonstrated activity in patients with advanced solid tumors in phase I trials. A multicenter, open-label phase II trial of oral vorinostat 200, 300 or 400 mg bid for 14 days followed by a 7-day rest until disease progression or intolerable toxicity was conducted. Patients with measurable, relapsed or refractory breast or non-small cell lung cancer who had received > or = 1 prior therapy or colorectal cancer who had received > or = 2 prior therapies were eligible. The response rate, safety and tolerability were evaluated. Sixteen patients (median age, 62 years; median 5.5 prior therapies) were enrolled. Six patients received 400 mg bid, six received 300 mg bid and four received 200 mg bid (14 days/3 weeks). Dose-limiting toxicities (DLTs) at the 400 or 300 mg bid levels were anorexia, asthenia, nausea, thrombocytopenia, vomiting, and weight loss. No DLTs were observed at the 200 mg bid level. Disease stabilization was observed in eight patients, but there were no confirmed responses. The median TTP was 33.5 days. Eleven patients discontinued due to clinical adverse experiences (AEs). The most common drug-related AEs were anorexia (81%), fatigue (62%), nausea (62%), diarrhea (56%), vomiting (56%), thrombocytopenia (50%) and weight loss (50%). Drug-related AEs > or = grade 3 included thrombocytopenia (50%), anemia (12%), asthenia (12%) and nausea (12%). Vorinostat in a daily oral schedule for 14 days/3 weeks was tolerable at 200 mg bid only, and no responses were observed in this study. Most patients, however, had limited drug exposure which did not allow a reliable efficacy analysis.
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PMID:Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. 1842 18

Patients with colorectal cancer present a number of supportive care challenges including those related to the underlying disease, such as gastrointestinal obstruction, nausea, anorexia, and fatigue, and those caused by the treatments, such as oral mucositis, neuropathy, and chemotherapy-induced diarrhea. Unique toxicities can accompany specific routes of administration of colon cancer drugs such as hand-foot syndrome with oral capecitabine and continuous infusion fluorouracil and biliary sclerosis with intrahepatic arterial floxuridine. The newer targeted therapies also present new toxicities, such as cardiovascular events and wound-healing complications with bevacizumab and rash and hypomagnesemia with cetuximab. Recent additions to the therapeutic armamentarium have presented new challenges, such as oxaliplatin-induced peripheral neuropathy, capecitabine-induced hand-foot syndrome, cetuximab-induced rash, and bevacizumab-associated arterial thrombotic events, bowel perforation, hypertension, and wound-healing complications. This article focuses on the prevention and management of several of these more common symptoms and toxicities.
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PMID:Supportive care in the management of colon cancer. 1863 90

We have retrospectively been collecting data on adverse reactions to FOLFIRI chemotherapy in our hospital from September 2005 to August 2006, by electronic medical records. The retrospective study was of 67 patients who received FOLFIRI for advanced colorectal cancer. Survey results showed high incidences of vomiting(58.2%), anorexia(91.4%), constipation (47.8%), diarrhea (61.2%) and alopecia(71.6%). The first cycle using FOLFIRI therapy, vomiting (20.9%), anorexia(53.7%), constipation ( 14.9%), and diarrhea (23.9%)were observed. We sought to minimize inter-individual differences in pharmaceutical care and drug consultation by clinical pharmacists and to ensure the accurate understanding of patients. We are sure that this kind of activity will help us to provide better pharmaceutical care for patients.
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PMID:[Preparation of a brochure for patients undergoing FOLFIRI chemotherapy based on survey of adverse reactions]. 1870 44

The present study was designed to retrospectively examine the efficacy of postoperative adjuvant chemotherapy in 107 patients with stage II primary colorectal cancer who underwent curative resection. The chemotherapy regimen was intravenous 5FU/LV in 30 patients (FL-IV group) and oral UFT/PSK in 77 patients (oral group). There were no significant differences between the FL-IV and the oral group with respect to the 3-year relapse-free survival rate, 5-year relapse-free survival rate, and 5-year overall survival rate, which were 82.4 vs. 83.0% (p=0.8546), 78.8 vs. 80.0% (p=0.756), and 81.6 vs. 92.8% (p=0.1609), respectively. Grade 3 adverse events that occurred in the FL-IV group were leukopenia in one patient (3.3%), nausea/vomiting in two (6.6%), anorexia in two (6.6%), diarrhea in one (3.3%), and fatigue in one (3.3%). No grade 3 or 4 adverse events were observed in the oral group. These results suggest that the oral regimen achieved equivalent efficacy to the FL-IV regimen in patients with stage II colorectal cancer, while improving their postoperative quality of life.
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PMID:Comparison between intravenous and oral postoperative adjuvant immunochemotherapy in patients with stage II colorectal cancer. 1894 20


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