Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irinotecan hydrochloride (CPT-11), a semisynthetic derivative of camptothecin, has been demonstrated to be active against solid tumors such as non-small cell lung cancer and colorectal cancer. Two combination phase I trials were undertaken to determine the maximum tolerated dose of CPT-11 in combination with cisplatin and vindesine in patients with advanced non-small cell lung cancer. All 46 patients (age 32-73 years) entered into these trials had a good performance status (Eastern Cooperative Oncology Group score, 0-1) and had received no prior chemotherapy or radiotherapy. In the first trial, 14 stage IV and 2 stage IIIb patients were studied; in the second trial 30 patients with stage IV disease were accrued. In the first trial, CPT-11 was given as a 90-min i.v. infusion on days 1 and 8 in combination with a fixed dose of cisplatin (100 mg/m2, i.v., on day 1) and vindesine (3 mg/m2, i.v., on days 1 and 8), every 4 weeks. The starting dose of CPT-11 was 25 mg/m2, and the dose was increased in increments of 25 mg/m2. In the second trial, the doses of either CPT-11 (days 1 and 8) or cisplatin (day 1) were escalated with a fixed dose of vindesine (same dose as the first study) given in a 4-week cycle. The starting doses of CPT-11 and cisplatin were 20 and 60 mg/m2, respectively, and the dose of either CPT-11 or cisplatin was increased in increments of 20 mg/m2. At least 3 patients were entered at each dose level in both trials. Use of granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor was not permitted in this trial. In the first trial, grade 4 granulocytopenia and grade > or = 3 diarrhea were dose limiting at 50 mg/m2 CPT-11, which represented the maximum tolerated dose. At the subsequent dose of CPT-11, 7 new patients were requited at the 50% reduced dose level of 37.5 mg/m2 on days 1 and 8. Nine patients were evaluated for response, and 4 of them achieved a partial response. In spite of a low dose of CPT-11 (25-37.5 mg/m2), the maximum concentration in plasma of CPT-11 (> 0.4 micrograms/ml) reached > 10-fold the in vitro concentration of CPT-11 required for 50% inhibition of growth. In the second trial, the dose-limiting toxicities were grade 4 granulocytopenia lasting for > or = 7 days and grade > or = 3 diarrhea.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Phase I clinical trial of irinotecan (CPT-11), 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin, and cisplatin in combination with fixed dose of vindesine in advanced non-small cell lung cancer. 816 91

MoAbs against tumour-associated antigens (TAA) may be useful for the treatment of colorectal cancer. Since an increased expression of TAA may lead to enhanced antibody-dependent cellular cytotoxicity we examined whether the cytokines IL-2, IL-4, IL-6, IL-10, IL-12, interferon-alpha (IFN-alpha), IFN-gamma, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor and tumour necrosis factor-alpha can influence EpCAM and LewisY expression on the surface of the colorectal carcinoma cell lines HT29, LoVo and SW480. We found that only IFN-alpha increased significantly whereas IL-4 decreased both EpCAM and LewisY expression. IFN-gamma significantly increased LewisY expression only. When tumour cells were treated with MoAb, the LewisY-specific MoAb BR55-2 down-regulated LewisY antigen expression, whereas MoAb 17-1A, which binds to EpCAM, up-regulated this TAA after 3 days of culture. The cytokines IFN-alpha or IFN-gamma combined with MoAb 17-1A enhanced further slightly the expression of EpCAM. In additional experiments with chemotherapeutic drugs commonly used for the treatment of colorectal cancer, we found that 5-fluorouracil, mitomycin-C and oxaliplatin up-regulated EpCAM and LewisY antigen expression. Raltitrexed enhanced LewisY and down-regulated EpCAM expression, whereas CPT-11 had no influence at all. The highest expression for EpCAM on HT29 cells was achieved by the combination of IFN-alpha, 5-fluorouracil and MoAb 17-1A. Our results may be useful for defining combinations of biological and chemotherapeutic drugs for the treatment of colorectal cancer. Further trials should evaluate to what extent these combinations enhance antibody-dependent cellular cytotoxicity.
 ...
PMID:Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression. 1116 91