Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this ongoing study is to determine the response and safety of a combination of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus doxorubicin as neoadjuvant therapy for stage IIIB breast cancer. Thirty-nine chemotherapy-naive patients were enrolled in the study. The median age was 54 years (range, 32 to 74 years), and the median Karnofsky performance status was 100. Gemcitabine 1,200 mg/m(2) was given on days 1 and 8, and doxorubicin 60 mg/m(2) on day 1, followed by surgery or radiotherapy. Ninety-seven of 117 cycles (83%) were administered at full dose. An overall response rate of 95% was obtained, with a complete response in 18% (seven patients) and a partial response in 77% (30 patients). Twenty-eight patients (72%) underwent breast surgery after a maximum of three cycles of neoadjuvant therapy. World Health Organization grade 3/4 toxicities included leukopenia in nine cycles (8%), neutropenia in 16 cycles (14%), febrile neutropenia in 11 cycles (9%), and anemia in two cycles (2%). The most important nonhematologic toxicity was grade 2/4 mucositis in 16 cycles (14%), and/or grade 2/3 diarrhea in 10 cycles (9%). Neoadjuvant therapy with gemcitabine plus doxorubicin results in a high tumor response rate with moderate oral and hematologic toxicity. Semin Oncol 28 (suppl 10):57-61.
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PMID:A phase II study of neoadjuvant gemcitabine plus doxorubicin in stage IIIB breast cancer: a preliminary report. 1151 35

The human teratocarcinoma-derived growth factor (TDGF)-1 gene encodes a 188-amino acid protein, cripto-1. The TDGF-1 gene is overexpressed in the majority of human primary colorectal carcinomas and hepatic metastases, in breast carcinomas and in testicular nonseminoma germ cell embryonal carcinomas. In the human embryonal carcinoma cell line NTERA-2 clone D1, a 2-kb TDGF-1 mRNA transcript is expressed. The present study shows that a 1.7-kb mRNA transcript lacking the first two exons of the TDGF-1 gene is expressed in the human colon carcinoma cell line GEO. This shorter mRNA is the only TDGF-1 transcript that is present in the majority of primary human colorectal carcinomas and hepatic metastases and in adult human tissues such as the pancreas, heart, stomach, mammary gland, skeletal muscle, liver and placenta. In contrast, in the kidney, brain, testis, ovary and spleen, the longer 2-kb TDGF-1 mRNA transcript is expressed. The putative shorter protein starts at a CUG codon 129 nucleotides downstream of the starting AUG codon of the longer protein. These data indicate the potential for differential transcriptional regulation of the TDGF-1 gene in different normal and tumor tissues.
Tumour Biol
PMID:A truncated form of teratocarcinoma-derived growth factor-1 (cripto-1) mRNA expressed in human colon carcinoma cell lines and tumors. 1155 58

Pancreatic cancer has extremely poor prognosis. However no satisfactory effective chemotherapy for this cancer has been established. Gemcitabine hydrochloride, a novel anti-tumor agent, had shown the remarkable clinical efficacy for pancreatic cancer. In April 2001, the indication for pancreatic cancer of this agent has been approved in Japan and it is expected to be widely and increasingly introduced for clinical use. This review summarizes the study results of gemcitabine mono-therapy for pancreatic cancer and discusses other possibility of the treatment by Gemcitabine with the reported data about its combination therapy with other anti-cancer drug or radiation.
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PMID:[Results of gemcitabine hydrochloride in the treatment for pancreatic cancer]. 1168 Dec 59

Since the introduction of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), pancreatic cancer may no longer be regarded as a completely chemotherapy-resistant tumor. Good treatment tolerability and a low incidence of side effects are clear advantages of single-agent gemcitabine and enable its integration into combination regimens. Currently, the most widely used regimens involve combination partners such as 5-fluorouracil (5-FU), cisplatin, and docetaxel. Combinations of gemcitabine with cisplatin or 5-FU appear comparably active and tolerable. Comparative analysis of multiple phase II studies performed with gemcitabine/cisplatin showed response rates in the range of 11.4% to 58% and median survival times of 7.4 to 10 months, whereas various gemcitabine/5-FU-based regimens achieved response rates of 3.7% to 25% and median survival times of 4.4 to 10.3 months. In view of the great variety of schedules and inconclusive treatment results, an optimal regimen for the combination of 5-FU and gemcitabine still needs to be defined. Although the combination of gemcitabine with docetaxel has demonstrated activity, data showing a clear survival benefit are not yet available. It is also premature to evaluate the activity of combinations with irinotecan or oxaliplatin. Four-drug regimens indicate a possible improvement in treatment outcome. However, their application may be limited to selected patients with good performance status.
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PMID:Gemcitabine-based combination treatment of pancreatic cancer. 1189 5

XK-469 is advancing to Phase I clinical trials. Preclinical studies were carried out to assist in clinical applications. DOSE-SCHEDULE ROUTE TESTING: Single dose i.v. treatment with XK-469 produced lethality (LD20 to LD100) above 142 mg/kg. Optimum treatment required total dosages of 350 to 600 mg/kg. Furthermore, high individual i.v. dosages (100 to 142 mg/kg) were poorly tolerated, producing substantial weight loss (8 to 18% of body weight), poor appearance, and slow recovery (8 to 12 days). A 1-hour infusion of dosages more than 140 mg/kg, or BID injections 6 hrs apart, did not reduce lethality. However, lower individual dosages of 40 to 50 mg/kg/injection i.v. were well tolerated and could be given daily to reach an optimum total dose with minimal toxicities. Likewise, 75 mg/kg/injection i.v. could be used every other day to reach optimal treatment. The necropsy profiles of deaths from toxic dosages were essentially identical regardless of schedule (deaths 4 to 7 days post treatment). The profiles were: paralytic ileus or gastroparesis; GI epithelial damage; and marrow toxicity. Interestingly, the key lethal events were rapidly reversible and simple to overcome with lower dosages given daily or every other day. Based on these results, the high dose, Q21 day schedule should be avoided in clinical applications. Instead, a split dose regimen is recommended (e.g., daily, every other day, or twice weekly). XK-469 was also well tolerated by the oral route, requiring 35% higher dosages p.o. to reach the same efficacy and toxicity as produced i.v.. CROSS-RESISTANCE STUDIES: XK-469 resistance was produced by optimum treatments of i.v. implanted L1210 leukemia over seven passage generations. This leukemia subline (L1210/XK469) had reduced sensitivity to VP-16 (with a 4.0 log kill in i.v. implanted L1210/XK469 compared to an 8.0 log kill against i.v. implanted L1210/0). It also had a reduction in the sensitivity to 5-FU (with a 2.0 log kill in the implanted L1210/XK469 compared to a 4.0 log kill against i.v. implanted L1210/0). Other agents were approximately as active against the resistant tumor, including: Ara-C, Gemzar, Cytoxan, BCNU, DTIC, and CisDDPT. No case of collateral sensitivity was observed; i.e., no agent was markedly more active against the resistant subline L1210/XK-469 than against the parent tumor in mice.
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PMID:Preclinical efficacy evaluations of XK-469: dose schedule, route and cross-resistance behavior in tumor bearing mice. 1200 90

Neoplasms of the biliary tract tree are uncommon and have a poor overall prognosis. Although numerous risk factors have been identified, little is known about the pathogenesis of these tumors, and no effective screening technique is available for early detection. Surgery remains the principal treatment modality and the only potential cure, with laparoscopy playing an increasingly important role in determining the resectability of these tumors. The role of postoperative adjuvant chemotherapy and radiation remains controversial. The efficacy of chemotherapy for advanced disease is relatively limited, with response rates of less than 10% for single-agent fluorouracil. Of the newer agents, gemcitabine (Gemzar) holds the most promise in the treatment of these difficult malignancies.
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PMID:Cancers of the gallbladder and biliary ducts. 1216 60

Although treatment of advanced non-small-cell lung cancer has been improved with the availability of such new agents as the taxanes, topoisomerase inhibitors, vinorelbine (Navelbine), and gemcitabine (Gemzar), platinum-based combination therapy has appeared to reach a threshold of therapeutic effectiveness. A paradigm shift in approach to non-small-cell lung cancer and other tumors may be heralded by the development of agents targeting specific biologic pathways in tumor development. Such new agents include antibody epithelial growth factor receptor (EGFR) inhibitors (eg, the monoclonal antibodies trastuzumab [Herceptin] and cetuximab [IMC-C225, Erbitux]) and EGFR tyrosine kinase inhibitors (eg, ZD1839 [Iressa] and OSI-774), angiogenesis inhibitors (eg, matrix metalloproteinase inhibitors), vascular endothelial growth factor (VEGF) inhibitors (eg, monoclonal antibody to VEGF ligand and small-molecule tyrosine kinase), and signal transduction inhibitors (eg, ISIS-3521, an antisense oligonucleotide to protein kinase C-alpha). A number of these agents have entered advanced-phase clinical investigation. It is likely that targeted therapy will have applications in combination with cytotoxic chemotherapy or radiation therapy at all stages of treatment, including maintenance therapy. It is even possible that these new biologic therapies will be used together as rational combinations (based on pathologic diagnosis) for advanced non-small-cell lung cancer.
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PMID:Targeted therapy in non-small-cell lung cancer. 1237 97

This phase II study evaluated the activity of gemcitabine (Gemzar) plus cisplatin (Platinol) as first-line treatment of advanced epithelial ovarian cancer. Forty-two chemonaive patients with advanced (stage III and IV) epithelial ovarian cancer received gemcitabine 1,250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, up to eight cycles. The median number of cycles completed was 5 (range 2-8). Of the 41 patients evaluable for tumor response, 20 had a partial response and nine had a complete response, for an overall clinical and pathologic response rate of 70.7% (95% CI 56.8-84.6%). Median overall survival for all 42 patients was 23.4 months (95% CI 15.9-29.9 months) and the median progression-free survival time was 10.4 months (95% CI 9.4-13.5 months). The combination was generally manageable. Hematologic toxicity (grade 3/4 neutropenia: 31.0/21.4%; grade 3/4 thrombocytopenia: 9.5/4.8%; grade 3/4 anemia: 11.9/0%) and nausea and vomiting (grade 3/4: 35.7/31.0%) were the most common toxicities. There was one toxic death (septic shock due to hematologic toxicity-induced infection). We conclude that gemcitabine plus cisplatin is active and feasible as first-line treatment of advanced epithelial ovarian cancer. Further clinical trials with the addition of gemcitabine to first-line treatment appear warranted.
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PMID:Phase II study of gemcitabine and cisplatin in chemonaive patients with advanced epithelial ovarian cancer. 1239 69

This paper reports a case of pancreatic tail cancer with peritoneal carcinosis that showed a good response to gemcitabine hydrochloride. A 52-year-old man, who had undergone a gastrojejunostomy for pancreatic tail cancer with peritoneal carcinosis, was referred to our hospital for anticancer therapy. Laboratory data on admission disclosed hypoalbuminemia and a high level of serum CA19-9 (156 IU/ml). These findings indicated that the patient was in a cancer cachexic condition. Gemcitabine hydrochloride treatment (1,000 mg/m2/week x 3/4 weeks) was started. Ascites disappeared after 2 courses of treatment, and the tumor was reduced (62% of the reduction rate) after 5 courses of treatment. Furthermore, the serum CA19-9 level and serum albumin value returned to normal, and performance status was improved to grade 1. The patient has been well for 15 months after the diagnosis of pancreatic tail cancer with peritoneal carcinosis. Gemcitabine hydrochloride may have not only reduced the tumor volume and improved cancer cachexic condition, but also prolonged the survival time in this case.
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PMID:[A case of pancreatic tail cancer with peritoneal carcinosis treated with gemcitabine hydrochloride]. 1246 99

Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and cisplatin are commonly used in the treatment of many solid tumors, although the impact of chemotherapy is limited in metastatic non-small cell lung cancer. However, in clinical practice, there is a minority of patients who can attain long-term survival. Upregulation of mRNA transcripts has been linked to chemoresistance, and in some instances, mRNA expression has been correlated with polymorphisms. Cisplatin resistance is directly linked to the nucleotide excision repair system, specifically to the transcription-coupled nucleotide excision repair pathway that involves genes that are deficient in rare inborn disorders such as Cockayne syndrome and xeroderma pigmentosum. Overexpression of ERCC1 correlates with poor survival in gemcitabine/cisplatin-treated non-small cell lung cancer patients. At the preclinical level, ERCC1 and XPD mRNA expression correlate with each other, and overexpression of XPD causes selective cisplatin resistance in human tumor cell lines. XPD polymorphisms have been associated with lower DNA repair capacity. In our experience, time to progression is significantly higher in gemcitabine/cisplatin-treated patients with the Lys751Gln genotype (9.6 months) than in those with the Lys751Lys genotype (4.2 months; P =.03). Other polymorphisms involved in parallel DNA repair systems may well provide the same information, indicating a high degree of biologic redundancy. The overexpression of the subunit M1 of ribonucleotide reductase (RRM1) has been linked to gemcitabine resistance in our retrospective assessment. Preliminary findings that a subset of gemcitabine/cisplatin-treated patients with low ERCC1 and RRM1 mRNA levels show a significantly longer survival and highlight the possibilities of individually tailored chemotherapy.
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PMID:Targeted therapy in combination with gemcitabine in non-small cell lung cancer. 1291 17


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