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)

Based on promising results with 5-FU/FA or 5-FU/IFN-alpha in colorectal cancer, a pilot study was initiated to evaluate the effects of the combination 5-FU/FA/interferon alfa (IFN-alpha) in patients with advanced pancreatic cancer. Patients received 9 million units (MU) IFN-alpha subcutaneously three times a week or 6 MU IFN-alpha once a week; 500 mg/m2 5-FU via an intravenous bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of FA, once a week. Fourteen patients, all previously untreated with chemotherapy, were enrolled; 13 (two females/11 males) were evaluable for response and toxicity (one too early). The median performance status was 80% (range, 60 to 100) and the median age 62 years. Besides the inoperable primary tumor, metastatic sites were liver, lung, and peritoneum. Three of 13 patients had a partial remission, three of 13 patients a minor response, and four of 13 patients no change. Three patients had progressive disease. Until now, no complete remission was seen. Median duration of response was 4+ months; median survival has not been reached yet. Of all patients there were three instances of World Health Organization grade 3 toxicity: fatigue (one of 13), nausea (one of 13), and diarrhea (one of 13); grade 4 toxicity did not occur. Although overall toxicity was moderate, most patients experienced a reduction of well-being. Therefore in all patients the dose of IFN was reduced (from 3 x 9 MU/week to 1 x 6 MU/week). Our preliminary data suggest that biochemical modulation of 5-FU with FA and IFN-alpha (reduced dosage) is effective in pancreatic cancer with moderate toxicity, warranting further study.
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PMID:Combination fluorouracil, folinic acid, and interferon alfa-2a: an active regimen in advanced pancreatic carcinoma. 155 50

The combination of folinic acid (FA) and 5-fluorouracil (5FU) is the most active systemic chemotherapy against advanced colorectal cancer. Experimental and clinical studies have suggested that the activity of 5FU can be improved by the addition of alpha-interferon (IFN). To evaluate the possibility of a double modulation of 5FU, a pilot study was conducted in the period July 1989-December 1989 with the following regimen: FA (200 mg/m2 i.v. bolus x 5 days) + 5FU (400 mg/m2 i.v. in 15 min x 5 days) + alpha-2b IFN (10 x 10(6) IU subcutaneously on alternate days). FA and 5FU administrations were repeated every 28 days; IFN was administered every week. In the 16 treated patients, 4 partial responses, 4 no changes, and 8 with progression of disease were observed, with an objective response rate of 25% (95% CI, 7.8%-55.1%). Median duration of response was 9.5 months, as was overall survival. Toxicity (fever, fatigue, neurotoxicity, stomatitis and diarrhea) was considerable and led to a reduction in IFN doses in 10/16 patients. Due to the unfavorable cost/benefit ratio, the study was closed and a new trial, with different doses and schedule of IFN, was started within the GISCAD (Italian Group for the Study of Digestive Tract Cancer).
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PMID:High dose alpha-2b interferon + folinic acid in the modulation of 5-fluorouracil. A phase II study in advanced colorectal cancer with evidence of an unfavourable cost/benefit ratio. 160 56

We tried a infusion of interleukin-2 (IL-2) of a relatively low dose via an intrasplenic arterial catheter connected to a chronometric infusion (IS-IL-2). Eighteen patients of colorectal cancer with metastases to the liver or lung or of unresectable hepatoma received a 24 hour continuous infusion with low dose recombinant of IL-2 (mainly 8 x 10(5) JRU/day) for 25-40 days. All patients tolerated this protocol of the therapy and the main toxic effects were fever and general fatigue. Such serious toxicity as previously reported by high dose IL-2 therapy was not observed. Data of hepatic and renal functions were normal. IS-IL-2 therapy induced a high incidence of eosinophilia (12/18) and thrombocythemia (12/18). Peripheral natural killer (NK) and LAK activities were augmented in all patients and total white blood cell counts were increased during IS-IL-2 therapy. An increase in IL-2 receptor expression of peripheral blood mononuclear cells and significant rises in numbers of Leu11 (CD16)+, OKM1(CD11)+ and OKIa1(HLA-DR)+ were observed. Of 18 patients 12 were evaluable for their response to therapy. Partial response (PR) was observed in one unresectable hepatoma and 11 demonstrated no change (NC) or progressive disease (PD). Six patients were not evaluable because of additional therapy (3 cases) or decreasing tumor cell markers having no measurable lesions (3 cases). Three patients of colorectal cancer from an unresectable group were presumed to have micrometastases to the liver as suggested by an elevated serum CEA level. After receiving IS-IL-2 therapy they demonstrated a decrease in the serum CEA level for more than 3 years after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical trials of intrasplenic arterial infusion of interleukin-2 (IS-IL-2) to patients with advanced cancer. 162 39

Cyclosporin A (CSA) is an immunosuppressive agent that in experimental models has antiproliferative activity against colon cancer and other human neoplasms. A phase II trial was conducted to evaluate CSA in refractory colorectal malignancies. CSA was administered at a starting dose of 7.0 mg/kg twice daily (total dose, 14 mg/kg/day) and escalated to tolerance. Of 18 patients with measurable disease, 17 were evaluable. All had been treated with one fluorouracil-containing regimen. The European Cooperative Oncology Group (ECOG) performance status was 0 or 1 in 17 of the 18 patients. No objective responses were seen. Four patients maintained stable disease lasting from 10 to 75+ weeks. Significant toxicity occurred in 9 of 17 (53%) patients. Dose reduction was necessary in 10 of 17 (59%). Sustained escalation beyond the initial dose was possible in only two cases. Toxicities included nausea and vomiting (71%), nephrotoxicity (41%), fatigue (35%), flu-like symptoms (29%), and neurotoxicity (18%). In the dose and schedule employed in this trial, CSA is ineffective in refractory colorectal cancer and produces significant toxicity.
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PMID:A phase II trial of cyclosporin A in the treatment of refractory metastatic colorectal cancer. 203 7

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

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.
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PMID:A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma. 238 96

High-dose interleukin-2 (IL-2) with or without lymphokine-activated killer (LAK) cells has been reported to have activity in certain solid tumors, but toxicity has usually required hospitalization for administration. The purpose of this trial was to determine the antineoplastic effect and toxicity of IL-2 administered at a lower dose in an outpatient setting. Eligibility criteria included measurable disease, Karnofsky performance greater than or equal to 70%, age greater than 18 years, and adequate bone marrow, renal, and hepatic function. The median age of 35 patients was 56 years (range, 20 to 75). Diagnoses included malignant lymphoma (ML), (nine patients), chronic lymphocytic leukemia (CLL) (eight), melanoma (eight), colorectal cancer (six), renal cancer (two), and breast cancer (two). The initial 18 patients were treated with 1 mg/m2 (3 x 10(6) U/m2 intravenous [IV] bolus) for five days every other week for a total of 4 treatment weeks (8 weeks total). The subsequent 17 patients were treated with 0.5 mg/m2 (1.5 x 10(6) U/m2). All patients were evaluable for toxicity, and 26 for tumor response. Toxicities included fatigue (71%), nausea (69%), hypotension (54%), fever (51%), chills (40%), weight gain (37%), pruritus or rash (31%), dyspnea (14%), azotemia (6%), confusion (6%), thrombocytopenia (6%), and myocardial infarction (3%). Four patients died from apparently unrelated causes within the first 2 weeks of treatment. Treatment was discontinued before the completion of 8 weeks of treatment because of progressive disease (12 patients), severe hypotension (three), azotemia (one), myocardial infarction (one), early death (four), and miscellaneous causes (two). IL-2 at 1 mg/m2 IV for five days is associated with moderate toxicity, but a dose of 0.5 mg/m2 is tolerable for outpatient administration. Three partial responses (PR) and one minor response (MR) lasting 1 to 17+ months have been observed in 12 patients with ML and CLL evaluable for response. One additional MR was observed in a patient with melanoma. IL-2 deserves further study in patients with ML and CLL.
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PMID:Phase II trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. 278 39

A total of 20 patients with advanced colorectal cancer received recombinant leukocyte interferon-alpha A (rIFN alpha A) either chronically (group I: twice a week up to 20 X 10(6) IU/m2 i.m.) or cyclically (group II: 1-4 periods of 8 consecutive days up to 20 X 10(6) IU/m2 i.m. daily at 20-days intervals) over a period of 12 weeks. There was 1 partial response, 1 mixed response and 1 patient with stable disease, whilst 17 patients had progressive disease. Median survival was 15.5 months. Survival was significantly shorter when the extent of hepatic disease was greater than 25% (P = 0.05), extrahepatic disease was extensive (P less than 0.005), alkaline phosphatase level was greater than 2 X normal (P less than 0.02), or performance status was less than 100% (P less than 0.001). Toxicity consisting mainly of fever, fatigue, anorexia and weight loss was serious in group I and minimal in group II. Administration of rIFN alpha A led to a "short lived" augmentation of natural killer (NK) cell activity. In the cyclically treated group this was a recurrent phenomenon whereas a marked lasting depression of NK cell activity was seen in chronically treated patients. Interferon-gamma production capacity was significantly stimulated during rIFN alpha A therapy. The differences in toxicity and immunostimulatory effects between the two schedules may be of importance in the design of further studies.
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PMID:Clinical and immunological evaluation of 20 patients with advanced colorectal cancer treated with high dose recombinant leukocyte interferon-alpha A (rIFN alpha A). 363 19

Ten patients with metastatic colorectal cancer after resection of the primary tumor were treated with high-dose recombinant leukocyte alpha-2 interferon. For a period of 12 weeks the patients received up to 20 X 10(6) IU/m2 im twice weekly. Follow-up varied from 6 to 11 months after stopping treatment. All ten patients were evaluable for tumor response and toxicity. There was one partial response. Nine patients showed growth of metastatic marker lesions. Only three of these patients qualified as having progressive disease (greater than 25% increase in tumor mass). The response rate was 10%, with a 95% confidence interval of 0.3%-44.5%. Toxicity proved considerable and consisted of flu-like symptoms, fatigue, anorexia, and weight loss. Fatigue was the single most important dose-limiting factor. There were no drug-related deaths. Three patients died 3, 5, and 7 months after stopping treatment. Median survival was 18 months.
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PMID:Phase II trial of high-dose recombinant leukocyte alpha-2 interferon for metastatic colorectal cancer without previous systemic treatment. 388 27

Twenty-one patients with metastatic colorectal cancer were treated with high-dose intravenous interferon alpha-2 (30-50 X 10(6) units/m2) administered daily for 5 consecutive days. Courses of therapy were repeated every 2 to 3 weeks. No tumor responses were seen among 15 evaluable patients. In two subjects, disease remained stable for 3 and 7 months, respectively. Toxicity was substantial and a de-escalation of dose was frequently required. Fevers, gastrointestinal symptoms, fatigue, leukopenia, and elevated serum transaminases were common. High-dose interferon was found to be ineffective in the treatment of metastatic colorectal cancer. A daily dose of 50 X 10(6) units/m2 was greater than the maximum tolerated dose in this group of patients.
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PMID:A Phase II trial of high-dose intravenous interferon alpha-2 in advanced colorectal cancer. 648 45


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