Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.
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PMID:A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. 16 75

5-Flourouracil (5-FU) and methyl-CCNU have demonstrated separate sensitivities in carcinoma of the large bowel. This study was an attempt to see if methyl-CCNU versus methyl-CCNU plus 5-FU would demonstrate different responses in advanced colorectal carcinoma. Forty-nine patients have been evaluated, 14 receiving methyl-CCNU and 35 receiving 5-FU plus methyl-CCNU. One partial response has been seen with methyl-CCNU alone in a patient with liver metastasis. Thirteen partial responses have been noted in patients treated with the two-drug combination. There was a significant difference in the median survival of the responders versus the nonresponders for the two-drug group. Side effects were expected: nausea and vomiting, leukopenia, and thrombocytopenia. Plasma carcinoembryonic antigen and urine arylsulfatase were measured in all patients and correlated well with response.
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PMID:Methyl-CCNU versus methyl-CCNU and 5-fluorouracil in carcinoma of the large bowel. 92 50

28 patients (26 with breast cancer and 2 with colon cancer) received mitomycin, mitoxantrone and methotrexate (MMM). Half the patients had grade III-IV leukopenia and 29% had grade III-IV thrombocytopenia. The median time of recovery to WHO grade 0 was 62 and 128 days, respectively. Thrombocytopenia and leukopenia were more frequent and longer lasting after the three-drug part of the therapy, which suggests a critical role for mitomycin in this toxicity.
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PMID:Unexpected prolonged myelosuppression after mitomycin, mitoxantrone and methotrexate. 141 93

Nine platinum analogs are currently in clinical development, including three that contain the diaminocyclohexane substituent and five that contain the cyclobutanedicarboxylato leaving group. Many of them have shown activity in at least one cisplatin (CDDP)-resistant cell line, most commonly L1210 murine leukemia. In addition, most were less nephrotoxic than CDDP in preclinical evaluations. While these agents share certain key structural similarities, there are important differences in their toxicity profiles that may be exploitable in future combination therapies. Though neuropathy has been a troubling toxicity with two of the three diaminocyclohexane (DACH) compounds, it differs in that it appears to be less chronic and cumulative with oxaliplatin (I-OHP), which is also associated with much less myelosuppression. Of the cyclobutanedicarboxylato compounds that are structurally related to carboplatin (CBDCA), there are several notable differences. For several compounds, isolated neutropenia has been dose-limiting and thrombocytopenia, which is common with CBDCA, has been uncommon. Like CBDCA, neurotoxicity has not been an issue with this group. Therefore, the potential for dose escalation with a colony stimulating factor (CSF) appears enhanced. Furthermore, promising early clinical leads, such as the substantial response rates in cervix and head and neck cancers with 254-S and in patients with colon cancer using circadian modulation of I-OHP, require careful evaluation. Preclinical synergy data are also cited that suggest other potential clinical leads. The development of a number of these agents has been complicated by unanticipated issues, including unexpected chronic dose-limiting neurotoxicity with ormaplatin (OP), formulation and stability problems with liposomal-neodecanoato-diaminocyclohexane platinum (II) (L-NDDP), and problematic nephrotoxicity with zeniplatin (ZP). However, several of these new compounds are likely to enter broader phase II and III development and should provide important information not only about the utility of the agents themselves but also about the predictive value of some of these preclinical models of CDDP resistance.
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PMID:The current status of new platinum analogs. 146 69

Based on recent preclinical data suggesting synergism between 5-fluorouracil (5-FU) and interferon alpha (IFN-alpha) and clinical activity of the combination therapy in colon cancer, 14 patients with advanced gastric cancer were treated with combination therapy of 5-FU and recombinant interferon alpha-2b (rIFN alpha-2b) (Intron A, Schering, Kenilworth, NJ, U.S.A.). The maximum tolerated dose was 5-FU 750 mg/m2/day given as a continuous infusion daily for 5 days followed by weekly bolus injection of the same initial daily dose, plus rIFN alpha-2b 5 X 10(6) U given subcutaneously 3 times weekly starting day 1 of 5-FU infusion. The dose-limiting toxicities were fatigue/weakness, diarrhea, and neurologic toxicities such as somnolence and confusion. The other common side effects were nausea, fever, leukocytopenia, thrombocytopenia, and the darkening of the skin. Of 13 evaluable patients, 4 had a partial response (duration 6, 14, 24, and 28 weeks). These data suggest that combination therapy of 5-FU plus rIFN alpha-2b is tolerable and has manageable side effects in patients with advanced gastric cancer. Further Phase II study will be needed to define the antitumor activity of this combination.
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PMID:Combination of 5-fluorouracil and recombinant interferon alpha-2B in advanced gastric cancer. A phase I study. 155 2

A phase II clinical study of 254-S, a new anticancer platinum complex for gastrointestinal cancers, was conducted by the 254-S Gastrointestinal Cancer Study Group consisting of 16 institutions. 254-S was administered at 100 mg/m2 by intravenous drip infusion. This administration was repeated at 4-week intervals. The cases in which 254-S could be administered at least two times were regarded as complete cases evaluable for tumor response; of 75 cases registered, 53 were complete cases (29 cases with esophageal cancer, 12 with stomach cancer and 12 with colon cancer). As a result, 15 partial responses (PR) were obtained in the 29 patients with esophageal cancer and 1 PR from the 12 patients with stomach cancer, for a 51.7% and 8.3% response rate, respectively. 5 PR (55.6%) were obtained in 9 esophageal cancer patients with prior chemotherapy, including 2 PR in 4 patients previously treated with cisplatin. Major toxic effects observed were hematotoxicity including thrombocytopenia (59.0%), leukopenia (68.9%) and anemia (57.4%) and gastrointestinal toxicity such as nausea and vomiting (63.9%) and anorexia (41.0%); since grade 3 or 4 thrombocytopenia was observed with an incidence of 27.9%, careful monitoring seems to be required during the treatment with this product. Abnormal parameter changes on renal function included elevations of BUN (18.0%) and serum creatinine (9.8%). Based on these results, it was concluded that 254-S is a useful anticancer agent for the treatment of esophageal cancer.
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PMID:[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for gastrointestinal cancers. 254-S Gastrointestinal Cancer Study Group]. 155 98

A Phase I clinical trial of 1-beta-D-arabinofuranosyl-5-azacytosine (ara-AC or fazarabine) given as a 72-h continuous infusion on a 21-day cycle was conducted in 27 adult patients with refractory cancer. The major toxicity was reversible granulocytopenia and thrombocytopenia. Dose-limiting toxicity was observed at a dose rate of 1.96 mg/m2/h in which Grade IV leukopenia (WBC less than 1,000/mm3) occurred in 4 of 11 patients and Grade IV thrombocytopenia (platelets less than 25,000/mm3) occurred in 3 of 11 patients. Plasma steady-state levels ranged from 0.13 to 0.6 microM for doses of 1.25 to 5.94 mg/m2/h. Mean total body clearance was 647 ml/min/m2. Minor clinical responses were seen in one patient with testicular cancer, one patient with colon cancer, one patient with breast cancer, and one patient with acute nonlymphocytic leukemia. Another patient with adenocarcinoma of unknown primary had stable disease during 13 cycles of therapy. Based on the results of this study, the recommended dose for Phase II studies of 1-beta-D-arabinofuranosyl-5-azacytosine administered as a 72-h continuous infusion is 2.0 mg/m2/h (48 mg/m2/day).
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PMID:Phase I and pharmacokinetic study of arabinofuranosyl-5-azacytosine (fazarabine, NSC 281272). 168 36

Nine patients with progressive, metastatic disease from primary carcinoma of the colon were entered into a phase I/II study using continuous intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and high dose melphalan (120 mg m-2). GM-CSF was given alone to six patients during the first part of the study to determine a dose that would produce a peripheral leucocyte count (WCC) greater than or equal to 50 X 10(9) 1(-1) and was initially given at 3 micrograms kg-1 day-1 and escalated to 10 micrograms kg-1 day-1 after 10 days. The infusion was discontinued when the WCC exceeded 50 X 10(9) 1(-1) and after a gap of one week, melphalan was given over 30 min. GM-CSF was recommenced 8 h later and was continued until the neutrophil count had exceeded 0.5 X 10(9) 1(-1) for greater than 1 week. One patient achieved a WCC greater than 50 X 10(9) 1(-1) with GM-CSF 3 micrograms kg-1 day-1, but the other five who entered this phase of the study required dose escalation to 10 micrograms kg-1. No toxicity attributed to GM-CSF was seen. After melphalan, the median times to severe neutropenia (less than 0.5 X 10(9) 1(-1] and thrombocytopenia (greater than 20 X 10(9) 1(-1] were 6 and 9 days respectively. The median durations of neutropenia and thrombocytopenia were 14 and 10 days respectively. All patients required intensive support with a median duration of inpatient stay of 24 days. There was one treatment related death due to renal failure. One complete and two partial remissions (33% response rate) were seen but these were of short duration (median of 10 weeks). This study demonstrates that GM-CSF given by continuous intravenous infusion produces significant increments of peripheral granulocyte counts at 3 and 10 micrograms kg-1 day-1 and is not associated with any toxicity. The duration of neutropenia and thrombocytopenia induced by high-dose melphalan appears to be reduced by the subsequent administration of GM-CSF to times which are at least as short as have been reported in historical series which have used autologous bone marrow rescue.
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PMID:Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer. 169 72

An early phase II multicentered study of YM 881 (zinostatin stimalamer) was conducted in 36 patients to investigate response and the safety of the drug in malignant tumors. The response could be evaluated in 18 patients, one with brain tumor, 2 with lung cancer, one with breast cancer, one with liver cancer, one with pancreatic cancer, 6 with gastric cancer, and 6 with colon cancer. PR was found in the patient with brain tumor. Major subjective unwanted effects were gastrointestinal symptoms. Objective evidence of hematological changes (thrombocytopenia, decreased hematocrit, and lymphocytopenia) was also obtained.
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PMID:[Early phase II study of YM 881 (zinostatin stimalamer) by intravenous injection. Research group for intravenous YM 881]. 182 83

Sixteen patients with metastatic carcinoma of the colon were treated with a regimen of leucovorin 200 mg/m2, given as a 10-min infusion followed by a median dose of 833 mg/m2 (range 500-1000 mg/m2) 5-fluorouracil every two weeks. For the 16 patients with proven metastatic disease, two-year survival exceeds 50%. Responses were: 2 complete; 4 partial; 4 minor; 3 progression; and 3 not evaluable but without progression to date. Toxicities include: 8 (50%) leukopenia; 9 (56%), 1 severe thrombocytopenia; 9 (56%), 2 severe, diarrhea; 9 (56%), 3 severe, nausea/vomiting; 8 (50%), 1 severe, stomatitis; 7 (44%) conjunctivitis; 6 (38%) alopecia; and 13 (81%), 3 severe, neurotoxicity. Leucovorin appears to exert a dose-dependent beneficial effect on both the response and survival produced by the intermittent high-dose 5-fluorouracil schedule. This benefit first appears to increase substantially when the leucovorin dose is increased from 120 to 200 mg/m2. Findings identify a testable candidate regimen for selected good risk patients. Full selection criteria remain to be identified.
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PMID:Dose-dependent leucovorin efficacy with an intermittent high-dose 5-fluorouracil schedule. 220 56


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