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

Ten previously untreated patients with gastric cancer were treated with etoposide, 120 mg/m2 intravenously (i.v.) on days 4, 5, and 6, Adriamycin, 20 mg/m2 i.v. on days 1 and 7, and cisplatin, 40 mg/m2 i.v. on days 2 and 8 (EAP). Etoposide, 240 mg/m2 on days 4, 5, and 6, was administered orally instead of intravenously in alternating cycles, and pharmacokinetic studies were performed in those who had previously undergone gastrectomy or who had tumor infiltrating the stomach to determine oral bioavailability. Nine patients had advanced measurable gastric cancer, and one patient had an elevated carcinoembryonic antigen after surgery for synchronous gastric and colon cancer. The median age was 54 years (range 38-69), and the median Eastern Cooperative Oncology Group (ECOG) performance status was 2 (range 0-3). Nine of 10 patients had poorly differentiated adenocarcinoma. Twenty-four cycles were administered to 10 patients, and hematologic data were available for 23 courses. ECOG grade 4 neutropenia and thrombocytopenia developed in 19 (83%) and 8 (53%) courses, respectively. Thirteen courses (54%) were complicated by fever requiring parenteral antibiotics. Two patients (20%) died due to neutropenic sepsis. The profound myelotoxicity observed in our study prompted us to terminate the investigation prior to completing accrual. The oral bioavailability of etoposide was 21% and 36% in the two patients who had had prior gastrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of etoposide, doxorubicin (Adriamycin), and cisplatin (EAP regimen) in advanced gastric cancer. 222 Jun 57

rTNF was administered to 28 patients with advanced metastatic cancers by continuous intravenous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 micrograms/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 micrograms/M2/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I trial of recombinant tumor necrosis factor (rTNF) administered by continuous intravenous infusion in patients with disseminated malignancy. 264 24

Twenty-five patients with disseminated cancer (nine with renal cell carcinoma, five with melanoma, three with Hodgkin's lymphoma and chronic myelocytic leukemia [CML], two with soft tissue sarcoma, one each with large-cell lymphoma, breast cancer, and colon cancer), 13 males and 12 females, aged 25 to 68, were treated with recombinant human interleukin-2 (rIL2) by continuous infusion and adoptive transfer of autologous lymphocytes activated in vitro with IL2. Patients underwent leukapheresis on days 1, 8, 15, and 22 of the treatment. Cells, bulk activated for 20 hours in serum-free culture medium with 1,000 U IL2/mL in transfusion transfer packs as culture vessels, were transfused the following day. The infusion of IL2 by continuous infusion for six days started immediately after each adoptive transfer for 4 weekly courses. The dose of IL2 was escalated weekly in each patient; starting doses of IL2 were also escalated in subsequent cohorts of patients until maximally tolerated doses were reached. Nine patients had objective tumor regressions (three with renal cell cancer, two with Hodgkin's lymphoma, and one each with melanoma, sarcoma, breast, and colon cancer). Six responses were partial, two were minor, and one was mixed. Responding patients were maintained with IL2 by continuous infusion for six days every 6 to 8 weeks, without adoptive cell transfer. The median duration of responses was 16 weeks (3 to 60 + weeks). Tumor regression was related to the dose of IL2 (greater than or equal to 3.4 x 10(6) U/m2/d for six days) and to the in vivo lymphoproliferative effects of the lymphokine, but not to the total number of cells adoptively transferred. Side effects of treatment were transient and quickly reversible. Renal, hepatic dysfunction, and dyspnea were directly related to the dose of IL2 and to lymphocytosis. Other toxicities were mild hypotension with mild fluid retention, oral mucositis, anemia, thrombocytopenia, fever, and fatigue.
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PMID:Recombinant interleukin-2 by continuous infusion and adoptive transfer of recombinant interleukin-2-activated cells in patients with advanced cancer. 266 33

The effect of leucovorin (LV) given in various doses and schedules on the in vivo antitumor activity and toxicity of 5-fluorouracil (5FU) was studied in two murine colon cancer lines, i.e., Colon 26 (relatively resistant to 5FU) and Colon 38 (5FU sensitive), maintained in Balb-c and C57B1/6 mice, respectively. Mice were treated weekly with 5FU at the maximum tolerated dose, alone and in combination with LV. In Colon 26, neither simultaneous administration of 5FU and LV nor 5FU combined with delayed administration of LV potentiated the antitumor activity of 5FU. LV given twice - 1 hr before (50 mg/kg) and then together (50 mg/kg) with 5FU (100 mg/kg) - gave significantly better delay of tumor growth of both tumor lines than 5FU did alone (100 mg/kg). No differences were found after a total LV dose of 100 or 200 mg/kg. Delayed administration of uridine (3500 mg/kg) allowed the use of higher 5FU doses, which improved the antitumor effect on Colon 26. Systemic toxicity led to moderate weight loss in treated mice, but was comparable for mice treated with 5FU alone or combined with LV. Hematological toxicity consisted of moderate leukopenia (nadir 40%), which was observed with the most active schedule and was less severe than with 5FU alone. This schedule did not cause thrombocytopenia, but after discontinuation the thrombocyte count showed an overshoot. Addition of uridine to this schedule reduced hematological toxicity only slightly. It is concluded that LV potentiated the antitumor activity of 5FU against two solid tumor lines, i.e., a relatively resistant and a sensitive murine colon carcinoma, and that toxicity was moderate.
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PMID:Schedule-dependency of in vivo modulation of 5-fluorouracil by leucovorin and uridine in murine colon carcinoma. 279 68

Escalating doses of recombinant human interleukin-2 (rIL-2) were combined with long-term cultured rIL-2 activated killer cells to treat patients with disseminated melanoma, renal cell cancer, and colon cancer. Twenty-four patients were entered, 12 with renal cell cancer, 8 with colon cancer, and 4 with melanoma; 23 were evaluable for efficacy and toxicity. The (dose-related) toxicities were moderate to severe and consisted of fever, chills, rigors, weight gain, hypotension, mild confusion, elevation of liver enzymes and serum creatinine, thrombocytopenia, and eosinophilia. No cardiac events (arrhythmias or myocardial infarction) were recorded. None of the patients were admitted to the intensive care unit, and no deaths occurred. Two partial responses were observed, one at relatively low doses of rIL-2 in a patient with renal cell carcinoma and one at the highest dose level in a patient with malignant melanoma. The maximally tolerated dose level of rIL-2 for this study was 6 X 10(6) U/m2 i.v./day. The recommended dose for further studies is 3 X 10(6) U/m2 i.v./day in three divided doses.
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PMID:Treatment of patients with advanced cancer using multiple long-term cultured lymphokine-activated killer (LAK) cell infusions and recombinant human interleukin-2. 279 92

Disease-oriented phase II trials of doxifluridine were performed in advanced colorectal, breast, renal, endometrial, stomach, and ovarian carcinomas. The dose schedule recommended by the phase I trial (12.5 g/m2 by continuous iv infusion over 6 hours once a week for 3 weeks followed by a 1-week rest) was chosen first: the initial dose was later decreased to 10 g/m2 due to the fact that several neurotoxic effects were reported. A total of 207 patients were entered: 137 patients who received at least two courses of treatment were evaluable for response. Therapeutic activity was demonstrated in breast cancer [two complete responses (CR) and 13 partial responses (PR) among 42 patients], colon cancer (seven PRs among 35 patients), and rectal cancer (six PRs among 23 patients). Some therapeutic activity was detected in ovarian cancer (one CR among nine patients), endometrial cancer (one PR among five patients), and stomach cancer (one PR among five patients). No significant activity was noticed in renal cancer (one PR among 18 patients). Nonhematological toxicity was evaluated according to World Health Organization criteria. Nausea and vomiting were recorded in 50% of the patients (Grade 3-4 in 5%), diarrhea was recorded in 20% (Grade 3-4 in 5%), and cutaneous and allergic reactions were recorded in 10% (Grade 3-4 in 2%). Myelotoxicity during the first treatment course was mild; median wbc and platelet count nadirs (x 10(9) cells/L) were 4.1 (range, 0.1-11) and 194 (range, 20-482), respectively. Nevertheless, some cases of acute leukopenia and thrombopenia were reported. Consciousness alterations and neurologic symptoms were the major side effects (72 of 173 evaluable patients), since treatment had to be interrupted in 34 patients and four lethal neurotoxic effects occurred. At the same total dose of doxifluridine, the risk of neurotoxicity significantly increases with age and with the weekly dose and to the contrary it decreases with increasing bilirubin level. Although activity was demonstrated, this treatment cannot be recommended because of major neurotoxicity. Further pharmacological studies seem warranted to define the optimal dosage schedule and to obtain a better therapeutic index.
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PMID:Phase II clinical evaluation of doxifluridine. 294 45

Mice bearing the murine colon carcinomas Colon 38 or Colon 26 were treated with 5-fluorouracil (5 FU) (60 or 100 mg/kg, respectively) weekly for 4 weeks at 08.30 hr or at 18.30 hr. The antitumor effect of treatment at 08.30 hr was significantly better for both types of tumors, but most pronounced for Colon 38. Toxicity was evaluated after administration of 60 mg 5 FU/kg. No thrombocytopenia was observed. Leucopenia was observed after treatment at 18.30 hr. It is concluded that the therapeutic efficacy of 5 FU against murine colon cancer is higher when 5 FU is administered at 08.30 hr.
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PMID:Diurnal variation in the therapeutic efficacy of 5-fluorouracil against murine colon cancer. 297 71

alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, blocks polyamine synthesis and has demonstrated antitumor activity against small cell lung cancer and colon cancer in cell culture and animal tumor models. To evaluate clinical efficacy and further define toxic effects of this new agent, phase II trials of DFMO were performed in previously treated patients with advanced small cell lung cancer and previously untreated patients with metastatic colon cancer. Oral DFMO was administered at a dose of 2.25 g/m2/day every 6 hours continuously to patients with small cell lung cancer. The same dose was given to patients with colon cancer but on a schedule of "3 weeks on, 1 week off" to avoid hearing loss. Evaluation of toxicity indicated that thrombocytopenia was seen only in patients receiving continuous DFMO who had received prior chemotherapy, while reversible hearing loss and gastrointestinal side effects occurred on both intermittent and continuous schedules in previously treated and untreated patients.
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PMID:Phase II trials of alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, in advanced small cell lung cancer and colon cancer. 301

Seventeen patients with advanced gastrointestinal cancer were treated with a combined chemotherapy of UFT with Adriamycin (UFT-A). The UFT-A regimen consisted of UFT, 600 mg/body daily. As for the Adriamycin, 10 mg/body was give intravenously from day 1-4 and was repeated every two weeks. Partial responses were seen in 7 cases (41%) (5 cases of gastric cancer, 1 case of colon cancer, and 1 case of bile-duct cancer) out of 17 evaluable patients (7 cases of gastric cancer, 3 cases of colon cancer, 4 cases of biliary tract cancer, and 3 cases of pancreatic cancer). Two patients had minor responses, and in eight patients their disease had stabilized. As for side effects, nausea and vomiting occurred in seven patients (41%), and anorexia was observed in eight patients (47%). Two patients (12%) showed a leukopenia count of less than 2,000/mm3 and none of these seventeen patients had thrombocytopenia, of less than 5 x 10(4)/mm3. Considering these results, UFT-A therapy appears to be useful in cases of advanced gastrointestinal cancer, especially gastric cancer.
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PMID:[Combination chemotherapy of UFT with adriamycin in advanced gastrointestinal cancer]. 311 75

Iproplatin was administered intravenously over 30 min daily for 5 consecutive days every 3 weeks to 80 evaluable patients with a variety of refractory solid tumor malignancies. Thrombocytopenia was the dose-limiting toxicity. Reversible drug-induced renal dysfunction was observed in 3 patients. One patient sustained mild ototoxicity but neurotoxicity was not encountered. Transient neutropenia, anemia, nausea, vomiting, diarrhea, elevations of liver enzymes, alopecia, and skin rash also occurred. The spectrum and severity of toxicity of iproplatin were found to differ from those of cisplatin. The maximally tolerated dose (MTD) was 45 mg/m2/day in patients who received prior chemotherapy and 65 mg/m2/day in those who did not. No complete responses occurred. Partial responses were obtained in 2/15 patients with colon cancer, 3/18 with breast cancer, 2/4 with carcinoma of unknown primary site and 1/2 with pancreatic cancer. Thirteen patients with lung (5), breast (4), colon (2), head and neck (1) and cervical (1) cancers had stable disease. Based on the different toxicity profiles between iproplatin and cisplatin and the possible antitumor efficacy of the former, phase II investigation of iproplatin has been initiated.
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PMID:Phase I--preliminary phase II trial of iproplatin, a cisplatin analogue. 319 85


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