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)

1. The rate of whole-body nitrogen flux, protein synthesis and protein breakdown were measured in patients with colorectal cancer (Dukes A-C) just before and 12 weeks after surgical removal of the tumour. The rates were determined from the urinary excretion of 15N in ammonia and in urea over a 9 h period after an oral dose of [15N]glycine. 2. The food intake during the 2 study days was identical for individual patients. The amount each received was determined from measurement of their intake of food ad libitum on the day preceding the pre-operative study and was consumed in six equal portions every 2 h during the experimental period. 3. No significant differences in the rates of nitrogen flux, protein synthesis and protein breakdown were found before and after tumour resection, whether calculated from the excretion of 15N in ammonia or in urea. Some changes in flux, both increases and decreases, were observed in individual patients after tumour removal but these could not be related to classification of the tumour, or to the presence of pre-operative anorexia or weight loss. 4. The results suggest that the primary tumour itself does not alter the overall rate of protein metabolism in the whole body.
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PMID:Whole-body protein turnover before and after resection of colorectal tumours. 682 46

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

Methoxymorpholinyldoxorubicin (FCE 23762) is a novel, highly lipophilic doxorubicin analogue. It possesses potent in vitro and in vivo antitumor activity including efficacy in multidrug-resistant tumor cell lines. It is also metabolically activated in vivo resulting in an 80-fold increase in potency over the parent drug. In this phase I study the drug was administered by i.v. bolus injection at 3-week intervals. Fifty-three patients with refractory solid tumors were treated; 133 courses of FCE 23762 were administered at doses ranging from 30 to 2250 micrograms/m2. The dose limiting toxicity was reversible myelo-suppression (granulocytopenia and thrombocytopenia), demonstrating a delayed nadir and recovery in comparison to doxorubicin. Other toxicities included transient elevation of hepatic transaminases, delayed and prolonged nausea and vomiting, mucositis, anorexia, fatigue, and diarrhea. Heavily pretreated patients demonstrated more myelosuppression than previously untreated patients at 1250 micrograms/m2. No cardiotoxicity was observed. Four objective tumor responses were seen: one complete response in a patient with pelvic recurrence of cervical cancer; one partial response in a patient with cutaneous and lymph gland metastases from head and neck cancer; and two minor responses in patients with liver metastases from colorectal cancer. Plasma concentrations of FCE 23762 and its 13-dihydro metabolite, FCE 26176, were measured in 20 patients at doses > or = 675 micrograms/m2, using HPLC with fluorescence detection. The area under the plasma concentration-time curve ranged from 30 to 80 ng/h/ml; plasma data suggested linear kinetics in the range of tested doses (although there was considerable interpatient variability). The maximum tolerated dose defined in this study using this schedule is 1500 micrograms/m2. A safe phase II dose for previously untreated patients using this schedule is 1250 micrograms/m2; however, this may actually be below the optimal dose for this patient population.
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PMID:Phase I clinical and pharmacokinetic study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762). 774 8

A multicentral cooperative study was conducted to evaluate the clinical efficacy and toxicity of l-Leucovorin (l-LV) and 5-fluorouracil (5-FU) in advanced colorectal cancer. The administration schedule was a two-hour intravenous infusion of l-LV (250 mg/m2) and an intravenous bolus injection of 5-FU (600 mg/m2), given one hour after the beginning of the l-LV infusion. Sixty-four patients were treated weekly for six weeks followed by two-weeks rest, and then evaluated for response. Complete response and partial response were obtained in 21 patients (32.8%). The median survival time was 12.8 months. The most prominent side effects were anorexia (57.8%), nausea and vomiting (56.3%), diarrhea (48.4%) and myelosuppression such as leucopenia (54.7%), thrombocytopenia (18.8%) and decreased hemoglobin (40.6%). These side effects, however, were within permissible levels. Severe toxicity was prevented by discontinuance of the treatment. From the present study, l-LV and 5-FU combination therapy seems to be a very promising and useful treatment for patients with advanced colorectal carcinoma.
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PMID:[A late phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal cancer. l-Leucovorin and 5-FU Study Group (Japan Western Group)]. 779 98

Twenty-two patients with metastatic colorectal cancer entered a Phase I-II trial to assess the maximum tolerable dose of alpha-2B-interferon administered intramuscularly three times per week in combination with fixed doses of 5-fluorouracil (450 mg/m2 IV for 5 days, and, from day 28, weekly) and folinic acid (200 mg/m2 IV before 5-fluorouracil) and the efficacy of this combination. Diarrhea and mucositis were the most frequent 5-fluorouracil-related toxicities and were > or = ECOG grade 3 in 23% and 18% of patients, respectively. Of 15 patients receiving interferon > or = 9 x 10(6) IU, 10 required interferon dose reduction mostly because of severe fatigue, anorexia, and declining performance status. Among 19 patients evaluable for response, 3 achieved a partial response and 1 a complete response for an overall response rate of 21% (95% confidence interval, 6-46%). In conclusion, our study demonstrates that IFN-alpha 2B at doses higher than 6 x 10(6) IU intramuscularly three times per week in the combination with 5-fluorouracil and folinic acid we used is too toxic for the majority of patients; this combination has moderate activity in metastatic colorectal cancer, although similar response rates have been reported, with less toxicity, with 5-fluorouracil plus folinic acid without IFN-alpha. A larger Phase III study would be required to determine the value of IFN-alpha in this combination.
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PMID:Double 5-fluorouracil modulation with folinic acid and recombinant alpha-2B-interferon. A phase I-II study in metastatic colorectal cancer patients. 819 3

We treated 14 patients with progressive metastatic colorectal cancer, using a combination of subcutaneous recombinant human interleukin-2 (4.8 x 10(6) IU/m2 three times daily on days 1 and 22, and twice daily on days 2 and 23, followed by 2.4 x 10(6) IU/m2 twice daily on days 3-5, 8-12, 24-26, and on 5 consecutive days per week, starting day 29), recombinant human interferon-alpha 2a (5.0 x 10(6) U/m2 thrice weekly), and 5-fluorouracil (750 mg/m2 i.v. bolus on days 15-19, and at weekly intervals thereafter, with a 1-week off-therapy interval every 4 weeks). Therapy was continued until disease progression occurred. Four (29%) and 8 (57%) evaluable patients achieved partial remission and stable disease, respectively; median response duration was 5.9 months. Toxicity of this regimen was moderate; the most common side effects were thrombocytopenia, leukopenia, nausea/vomiting, anorexia, malaise and fevers in all patients, along with diarrhea (63%) and mucositis (54%). Less than 10% of patients developed WHO grade IV toxicity; no toxic deaths occurred. Efficacy of this combination was not substantially different from alternative 5-fluorouracil-based regimens.
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PMID:Treatment of metastatic colorectal cancer patients with 5-fluorouracil in combination with recombinant subcutaneous human interleukin-2 and alpha-interferon. 819 11

In the present multi-center cooperative phase II study, in which 16 institutions participated, PJ-203 and mitomycin C were concomitantly infused into the hepatic artery of patients with metastatic liver cancer and the tumor response and safety of the combined therapy were examined. Of 81 patients treated with PJ-203, 52 patients were complete cases in which bidimensionally measurable lesions could be assessed for anticancer effect in accordance with the Direct Evaluation Criteria of Chemotherapy. The number of treatments given to the complete cases until the assessment of therapeutic effect ranged from 1 to 11 times, with the mean of 3.1 times. The overall response rate was 48.1% (25/52). The response rate for each primary lesion was 68.8% (11/16) for stomach cancer, 40.7% (11/27) for colorectal cancer and 33.3% (3/9) for other types of cancer including the gallbladder. The 25 patients with CR or PR, a 50% decrease in tumor size was confirmed after the treatment ranged from 1 to 5 times, with the treatment periods of 2 to 3 weeks. Adverse reactions were found in 56 (69.1%) out of 81 patients assessed for safety. Relatively frequent symptoms were pain in 49.4% (40/81), nausea and vomiting in 33.3% (27/81), fever in 30.9% (25/81) and anorexia in 6.2% (5/81). Principal abnormal laboratory values included a transient elevation of GOT (26.3%), GPT (22.5%), LDH (12.7%) and Al-p (8.8%). Blockade of blood flow could be observed by angiography when the amount of PJ-203 infused was in the range from 180 to 900 mg as degradable starch microspheres. The blood flow blockade could be observed most frequently at the amount of 600 mg (37.7%). The period attaining over 50% of tumor response in 25 complete cases was 42 days as a median. After the treatment was initiated in 81 patients, 50% survival duration and one-year survival rate averaged 277 days and 35.7%, respectively. The corresponding figures for each primary cancer were 419 days and 51.0% for patients with liver cancer metastasized from colorectal cancer, against 239 days and 11.8% for those with liver cancer metastasized from stomach cancer.
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PMID:[Multi-center cooperative phase II study of combined infusion of PJ-203 (degradable starch microspheres) into hepatic artery in metastatic liver cancer]. 821 76

A clinical study of the combination of cis-diamminedichloroplatinum [II] (CDDP) and 5-fluorouracil derivatives was conducted in advanced cancer of the alimentary tract. The regimen consisted of CDDP 50 mg/body/day (day 1-2, continuous infusion), 5-fluorouracil 500-750 mg/body/day (day 2-7, continuous infusion) and UFT 400 mg/day (day 8-28) on 1-3 courses. Thirty patients could be evaluated. The response rate was 25% (2/8) in cases of esophageal cancer, 31% (4/13) in gastric cancer and 33% (3/9) in colorectal cancer, with an overall response rate of 30% (9/30). A comparatively higher response rate was obtained in lymph node metastases (46%) and liver metastases (50%). Anorexia, nausea/vomiting and leukocytopenia were frequently observed, but almost all were well tolerated and recovered except two cases with severe leukocytopenia and nephrotoxicity. Based on these results, this combination chemotherapy seems to be useful for advanced cancer of the alimentary tract.
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PMID:[Clinical efficacy of cis-diamminedichloroplatinum [II] and 5-fluorouracil (UFT) in advanced cancer of the alimentary tract]. 834 32

Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV.
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PMID:[Phase I study of 5-fluorouracil and l-leucovorin]. 845 86

Medical records have often been found to be less reliable than interviews to patients when data on the initial signs and symptoms of cancer, and the out-of-hospital diagnostic process are sought; in spite of this, a large body of research on "diagnostic delay" in cancer is based on clinical records. As part of a study on delay in neoplasms of the digestive tract we analyzed the agreement on the type and date of the initial symptom between hospital records and a structured personal interview. Records were abstracted for a random sample (N = 60) of 183 patients interviewed. Concordance on the date of the first symptom was deemed to exist if the difference was +/- 30 days. The Kappa index (kappa) and the overall proportion of agreement (with its corresponding 95% confidence interval) were used. Medical records and structured personal interviews were concordant on the type of the first neoplastic symptom in only 61% of cases (kappa = 0.50): 67% in esophagus cancer (kappa = 0.49), 60% in stomach cancer (kappa = 0.52), and 61% in colorectal cancer (kappa = 0.50). Records underestimated the occurrence of anorexia as first symptom and overestimated weight loss and dysphagia. Only 56% of cases were date-concordant, the agreement being lower in colorectal cancer (46%) than in esophageal (67%) and stomach cancer (75%). Records indicated the first symptom to have occurred at a later date than interviews in 33% of cases; overall, a study based on hospital records would have underestimated the symptom to diagnosis interval by 2.2 months per patient. Only 40% of cases were totally (symptom and date) concordant. Marked discrepancies may exist between the information contained in medical records and what patients report during a structured interview. The quality of medical records data on the duration and nature of cancer symptoms should be assessed before its use in etiologic and evaluative research.
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PMID:Disagreement between hospital medical records and a structured patient interview on the type and date of the first symptom in cancers of the digestive tract. 855 51


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