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)

MAb-PAM4 is an anti-MUC1 antibody that has been shown to be reactive with 85% of pancreatic adenocarcinomas with no reactivity with normal pancreas or other tissues. Initial clinical studies have shown excellent targeting with high tumor/nontumor ratios. Gemcitabine, an analog of deoxycytidine, is currently a frontline treatment for pancreatic cancer. Acting via a number of metabolic pathways, gemcitabine is also a powerful radiosensitizer. Combined-modality, chemo/radiosensitization with gemcitabine and low dose (131)I-PAM4 radioimmunotherapy was performed to determine if a more effective treatment procedure could be developed. Athymic nude mice bearing large (1 cm(3)) CaPan1 human pancreatic tumors were given a single treatment cycle consisting of gemcitabine, 333 mg/m(2) administered on Days 0, 3, 6, 9 and 12 by intraperitoneal injection, along with either 100 or 200 microCi, (131)I-PAM4 administered on Day 0 by intravenous injection. Gemcitabine did not interfere with the biodistribution of radiolabeled antibody. Specific tumor targeting was observed for (131)I-PAM4, with a tumor/blood radiation dose ratio of 2.6 over the first 14 days. Gemcitabine alone and low dose radioimmunotherapy alone, each had no affect upon tumor growth; no statistical differences were noted in comparison to the untreated group. When combined, however, a statistically significant (p = 0.0324), synergistic anti-tumor effect was observed. Median survival time doubled for the combined treatment regimen compared to single modality treatment groups. The combined treatment modality was well tolerated by the mice. Our data show that combined gemcitabine with radioimmunotherapy may provide an improved alternative for the treatment of pancreatic cancer, achieving successful anti-tumor effects with low toxicity.
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PMID:Combined gemcitabine and radioimmunotherapy for the treatment of pancreatic cancer. 1177 94

We sought to determine whether gemcitabine, a new pyrimidine antimetabolite, could inhibit the growth of human osteosarcoma cells (OS) in vitro and in vivo. Four human OS cell lines (MG-63, TE-85, SAOS-2 and SAOS-LM7) were used to assess the activity of the drug in vitro. Gemcitabine caused growth inhibition and cell death in all four cell lines as measured using the MTT and colony-forming assays (IC(50) = 6.5 nM-9 microM and 7-14 nM, respectively). Using our newly developed human SAOS-LM7 OS lung metastasis mouse model, we assessed the in vivo activity of gemcitabine given i.p. and intranasally (i.n.). Mice were treated twice weekly for 3 weeks and then once weekly for 3 weeks using either i.p. or i.n. gemcitabine starting 4 weeks after tumor cell injection. The i.p. injection, at 120 mg/kg, resulted in a decrease in lung weights and the size of the nodules. However, no significant reduction in the number of metastatic nodules was seen (control median: >200 versus gemcitabine median: 150, p = 0.084). In contrast, the number of lung metastases was significantly decreased in mice that received i.n. gemcitabine at 15 (median: 1; range: 0-115, p<0.005) and 12 mg/kg (median: 41; range: 7-163, p = 0.005) when compared with control mice (median: >200). Intranasal therapy is a non-invasive method of drug delivery and has the advantage of targeting the lung, resulting in a higher drug concentration in the tumor area. In our study, i.n. instillation of gemcitabine inhibited the growth of lung metastases at an 8- to 10-fold lower dose than that used i.p. and appeared to be more effective in eradicating OS lung nodules. Because the lung is the most common site of OS metastasis, our data suggest that i.n. gemcitabine may be a novel therapeutic approach in the treatment of OS lung metastases.
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PMID:Eradication of osteosarcoma lung metastasis using intranasal gemcitabine. 1190 8

Most cytotoxic drugs have gross effects on the immune system, such as neutropenia and lymphopenia. However, their effects on tumor-specific immune responses are unknown. Gemcitabine is a nucleoside analogue that is frequently used to treat non-small cell lung cancer. It is also active in other malignancies, either alone or in combination with cisplatin. Here, we investigate its effects on antigen-specific antitumor immunity using a murine tumor cell line transfected to express influenza virus hemagglutinin (HA). CD4(+), CD8(+), and B220(+) lymphocyte numbers all decreased during chemotherapy (120 microg/g, i.p., every third day for five doses), but B cells were selectively depleted. Gemcitabine induced a profound suppression of the IgG antibody response to HA, and this was unrelated to tumor size. In contrast, in vitro T-lymphocyte recall responses to the class I- and class II-restricted dominant peptide epitopes of HA were enhanced in tumor-bearing, gemcitabine-treated mice. We found that gemcitabine was >2-fold more potent in its ability to inhibit B-lymphocyte proliferation compared with T-lymphocyte proliferation. Thus, gemcitabine does not appear to be detrimental to specific antitumor cellular immunity and may be useful in combination chemo-immunotherapy protocols. In contrast, vaccination protocols requiring a humoral immune response for maximal efficacy may be compromised in patients treated with gemcitabine.
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PMID:Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy. 1195 96

Gemcitabine is a new deoxycytidine derivative that shows a distinguishing, potent antitumor activity against various human tumor lines transplanted to nude mice. We have investigated the antitumor activity of gemcitabine combined with cisplatin (CDDP) or vindesine (VDS) using a lung cancer line, H-74, that was insensitive to almost all antitumor drugs and relatively insensitive to gemcitabine. We found that the antitumor effects of gemcitabine combined with CDDP or VDS were more potent and lasted longer than that of each drug alone, without an increase in side effects such as body weight loss. In this study, the antitumor activity of combined gemcitabine with topotecin (CPT-11) was evaluated using a similar method for 8 weeks, including a 4-week treatment period and a subsequent 4-week drug-free period, with reference to tumor growth inhibition rate, histological changes, and side effects. The treatment combining gemcitabine with CPT-11 administered at each 1/2 MTD showed an additive effect at 4 and 8 weeks after start of administration. Furthermore, no remarkable side effects were observed. Since these study results demonstrated that gemcitabine combined with CPT-11 increased and prolonged the antitumor activity without increasing side effects such as body weight loss, it is expected that CPT-11 could be one of the useful drugs used in combination with gemcitabine for lung cancer therapy.
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PMID:[Antitumor activity of combination treatment combining gemcitabine with topotecin against human lung cancer xenografted in nude mice]. 1197 42

Gemcitabine is a cytosine arabinoside (Ara-C) analog with activity in many human tumor systems. We evaluated the drug's activity in resistant or relapsing multiple myeloma. Gemcitabine 1000 mg/m2 was administered as a 30 minute infusion on days 1, 8, and 15 of a 28-day cycle. No dose escalations were permitted and dose reductions were scheduled for hematologic toxicity. Twenty-nine eligible patients were entered into Southwest Oncology Group (SWOG)-9803. One patient received no treatment and 5 patients had inadequate response assessments. The major toxicity was hematologic with grade 3/4 neutropenia in 9 and grade 3/4 thrombocytopenia in 15 patients. No responses were seen. Stable disease was confirmed in sixteen patients (57%). Median survival was eight months. Gemcitabine as utilized in this trial has shown little activity and is not to be strongly considered for future multiple myeloma trials.
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PMID:The evaluation of gemcitabine in resistant or relapsing multiple myeloma, phase II: a Southwest Oncology Group study. 1200 87

Gemcitabine is a pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors including bladder, non-small cell lung and pancreatic cancers. Gemcitabine is a potent radiosensitizer of human tumor cells. This review summarizes preclinical studies designed to elucidate the mechanism of action of gemcitabine with ionizing radiation. Phase I-II ongoing trials of combination of radiation therapy and gemcitabine are trying to determine the optimal dose and schedule which could be used in daily clinical activity. The mechanism of radiosensitization is thought to be simultaneously gemcitabine-induced dATP (deoxyadenosine triphosphate) depletion and cell cycle redistribution into the S phase. Although there are no real study which has proven supra-additive combination, the recent acute side effects in several clinical studies oblige physicists to determine with precision the maximum tolerated dose of gemcitabine in association with ionizing radiation. Radiosensitization conditions can be obtained either with a long exposition to a low concentration or a short exposition to a high concentration. Radiation sensitivity begin to be detected four hours after treatment for 48 hours. A dose about 100 mg/m2/week of gemcitabine could be used with radiation therapy according to recent phase I results. This limiting dose is approaching to a radiosensitization context where the effect of one agent is increased by another agent which is inactive or poorly active for the effect under consideration. In this type of regimen, the two modalities do interact with a frequent inhibition of recovery from potentially lethal damage and a probably increase of late side effects of radiation therapy. In contrast, radio-chemotherapy combination is used for a therapeutic advantage when the drug by itself is active against the tumor but does not enhance late side effects of radiation on the critical normal tissues within the irradiated volume. Gemcitabine surely is a strong radiosensitizer even at low doses with future extended combined modality therapeutic indications. The ultimate goal of combined treatments should be an increased therapeutic ratio.
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PMID:[Gemcitabine and ionizing radiations: radiosensitization or radio-chemotherapy combination]. 1201 38

The treatment of advanced non-small cell lung cancer requires histologic proof of diagnosis, careful staging, and assessment of each patient's performance status and comorbidities. For patients with stage IIIB (pleural effusion) and stage IV disease who have a Cancer and Leukemia Group B performance status (PS) of 0 to 1, appropriate management consists of combination chemotherapy with a platinum (either cisplatin or carboplatin) combined with paclitaxel, gemcitabine, vinorelbine, docetaxel, or CPT-11. Dosages and schedules previously established by large phase II or phase III studies should be followed. Variations in the toxicity patterns, schedules of administration, and economic considerations should guide the selection of the specific regimen. For patients who maintain a good performance status after first-line chemotherapy, second-line treatment may be considered. Current evidence supports the use of docetaxel as second-line treatment if the patient has not previously received this drug. Gemcitabine and paclitaxel may also have activity in this setting. Vinorelbine, ifosfamide, and CPT-11 appear to be inactive as second-line therapy for patients who have previously received platinum-based chemotherapy. For patients with a PS of 2, single-agent chemotherapy with vinorelbine, gemcitabine, or a combination of the two should be considered. Patients with poor performance status should be treated with supportive measures designed to relieve pain and acute complications because any tumor-directed therapy has limited benefit. Special situations exist in which curative therapy for metastatic disease is a possibility. Patients who present with solitary sites of metastatic disease, particularly after a long disease-free interval and in the CNS may undergo definitive surgery or radiotherapy with curative intent. Some have also reported favorable outcomes for patients with solitary adrenal or bone metastases as well. Surgical treatment or definitive radiotherapy should not be employed unless a thorough restaging evaluation is performed that includes computed tomography scan of the chest and abdomen through adrenals, brain magnetic resonance imaging, and positron emission tomography scan. A plethora of new agents targeting angiogenesis, tumor invasiveness, the hypoxic environment of tumors, and the cell cycle are currently in development.
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PMID:Advanced non-small cell lung cancer. 1205 40

Optimal therapy for pancreatic adenocarcinoma requires surgical removal with tumor-free margins. Superior outcomes have been reported for high-volume centers incorporating a multidisciplinary approach. Postoperative ("adjuvant") chemotherapy and radiation should be considered in patients with successfully resected primary tumors. Combined modality treatment with chemotherapy and radiation should be considered for locally advanced, unresectable tumors. Gemcitabine can provide symptom relief and a modest improvement in survival for patients with metastatic disease. Strict attention to relief of symptoms such as pain, depression, anorexia/cachexia, and jaundice is essential in all patients with pancreatic cancer. All patients with pancreatic cancer should be encouraged to enter clinical trials of new therapies, given that long-term survival for all stages remains poor.
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PMID:Pancreatic cancer. 1205 45

Gemcitabine has been reported to be an active agent in pancreatic cancer. Recent applications have included the use of a fixed-dose rate regimen in patients with advanced pancreatic cancer based on the observation that deoxycytidine kinase is saturated at the plasma gemcitabine concentrations achieved with standard infusion, thereby limiting the accumulation of intracellular gemcitabine triphosphate. In a Phase II study, this regimen was associated with survival rates better than those typically observed in patients with advanced disease. Gemcitabine also has been assessed as a radiosensitizer in locally advanced cancer and although toxicity was significant, objective responses were observed and included tumor response, which permitted curative resection. Future directions in therapy for pancreatic cancer include the development of agents targeting signal transduction pathways and nuclear transcription factors based on the continually improving understanding of the role of molecular events in carcinogenesis.
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PMID:New applications of gemcitabine and future directions in the management of pancreatic cancer. 1220 75

A phase II study was undertaken to determine the safety of combining flutamide with gemcitabine, with response rate being the primary end point. Twenty-seven patients with histologically proven, previously untreated, unresectable pancreatic adenocarcinoma received gemcitabine, 1 g m(-2) intravenously on days 1, 8 and 15 of a 28 day cycle, and flutamide 250 mg given orally three times daily. Treatment was halted if there was unacceptable toxicity, or evidence of disease progression. Toxicity was documented every cycle. Tumour assessment was undertaken after cycles 2 and 4, and thereafter at least every additional four cycles. One hundred and seventeen cycles of treatment were administered, median four cycles per patient (range 1-18). Gemcitabine combined with flutamide was well tolerated, with most toxicities being recorded as grade 1 or 2 and only nine treatment cycles associated with grade 3 toxicity. The most frequent toxicity was myelosuppression. One case of transient jaundice was recorded. The commonest symptomatic toxicity was nausea and vomiting. The response rate was 15% (four partial responses), median survival 6 months and 22% of patients were alive at 1 year. These results suggest antitumour activity of the combination therapy to be equivalent to single agent gemcitabine.
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PMID:Phase II study to evaluate combining gemcitabine with flutamide in advanced pancreatic cancer patients. 1223 52


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