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)

Piritrexim is a new antifolate that has shown activity in methotrexate-resistant tumors. Gemcitabine is an antimetabolite similar in structure to cytosine arabinoside with early studies demonstrating activity in a variety of cancers. It also has apparent synergistic activity with antifolates from initial work in tumor models. Paclitaxel is an antimicrotubule agent that has a wide spectrum of activity against a variety of solid tumors. The combination of gemcitabine, paclitaxel, and piritrexim was assessed in this phase I trial. Thirty patients were enrolled. The starting doses were piritrexim 25 mg orally twice daily (days 1-4, 15-18), paclitaxel 75 mg/m2 (days 1, 15), and gemcitabine 750 mg/m2 (days 1, 15), which then was escalated in a stepwise fashion. Four patients achieved stable disease while on study, whereas one patient with a poorly differentiated neuroendocrine tumor achieved a partial response. The main toxicity was myelosuppression. The maximum tolerated dose was thought to be piritrexim 25 mg orally three times daily (days 1-4), paclitaxel 150 to 175 mg/m2 (days 1, 15), and gemcitabine 1,000 mg/m2 (days 1, 15). The combination of these new antifolates with paclitaxel and gemcitabine appears safe and should be considered for phase II trials in known responsive tumors such as transitional cell carcinomas.
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PMID:Gemcitabine, Paclitaxel, and piritrexim: a phase I study. 1279 1

We report on 4 cancer patients with transient unspecific elevations of the serum tumor markers CA 19-9, CEA, CA 125 and CA 72-4, respectively. In one patient cholangitis due to biliary obstruction induced a significant transient increase of CA 19-9, in another patient HUS, probably as a severe complication after Mitomycin-C + Gemcitabine therapy resulted in a significant increase of serum CA 125. One patient demonstrated an extensively elevated and inexplicable serum CA 19-9 concentration (9450 u/ml) during a period of abdominal pain with continuous decrease and finally normalization within the following 5 years. Also inexplicable is an unexpected remittent increase of serum CA 72-4 in the course of chemotherapy after gastrectomy for gastric carcinoma. The presented data underline the necessity of interpreting serum courses of tumor markers only in the light of all available clinical data, imaging data and other laboratory tests in order to avoid misinterpretations.
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PMID:Atypical courses of serum tumor markers--4 case reports. 1282 Mar 11

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

We report the case of 75-year-old man with advanced pancreatic cancer who was successfully treated with gemcitabine. The patient was admitted to our hospital suffering from anorexia and body weight loss. CT and ERCP showed pancreatic tail cancer with Schnitzler metastasis. We judged that a curative operation was impossible. Gemcitabine was infused over 30 minutes on an outpatient basis (1,000 mg/m2/week x 3/4 weeks). After 4 courses, the tumor was reduced and the tumor markers decreased. Furthermore, the patient can take sufficient meals without any adverse effects. The patient continues to undergoing the therapy with gemcitabine, and his quality of life has been preserved.
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PMID:[A case of advanced pancreatic cancer treated with gemcitabine hydrochloride]. 1293 71

Serum carbohydrate antigen 19-9 (CA 19-9) has been identified as a useful tumour marker for diagnosis of exocrine pancreatic carcinoma, but its value for evaluating the response to chemotherapy with gemcitabine is not clear. Tumour regression in pancreatic carcinoma is hard to determine due to massive desmoplastic tissue. Furthermore, objective tumour response does not automatically transcribe into better survival. Therefore, clinical benefit response, a composed parameter consisting of factors like performance status, pain, and body weight was integrated in evaluating tumour response. The aim of this prospective study was to evaluate the usefulness of serial CA 19-9 measurements as a biochemical response marker and an outcome prognostic parameter in patients with advanced pancreatic cancer receiving gemcitabine treatment. A total of 46 consecutive patients (median age 66 years) suffering from histologically proven locally advanced or metastatic adenocarcinoma of the exocrine pancreas were analysed. Gemcitabine was applied for a median of 23 courses (range 6-76). Two patients achieved an objective complete remission, five an objective partial remission (overall response, OR=15.2%), while objective stable disease was documented in 19 and objective progressive disease in 20 patients. Patients with a decrease of >20% of the baseline CA 19-9 level after 8 weeks of chemotherapy had a significantly better median survival than patients with a rise or a decline <20%. The response of CA 19-9 >20% during chemotherapy was the only independent predictor of survival in a multivariate analyses. In contrast, neither objective tumour response nor clinical benefit response showed this level of significance. In conclusion, kinetics of CA19-9 serum concentration serves as an early indicator of response to gemcitabine chemotherapy in advanced pancreatic cancer.
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PMID:Prognostic value of CA 19-9 levels in patients with inoperable adenocarcinoma of the pancreas treated with gemcitabine. 1456 9

The treatment of patients with metastatic soft tissue sarcomas (STS) is complex. There are limited agents available and many are associated with significant toxicity. When evaluating a patient with metastatic disease, physicians should ask themselves whether there is a role for surgery to render the patient free of disease. Combination chemotherapy in patients who have not received chemotherapy in the adjuvant setting is one option, particularly in a young patient with a good performance status. Sequential single-agent therapy for patients who are more elderly or debilitated by their disease may be more appropriate. Gemcitabine appears to be an agent with activity, particularly in patients with leiomyosarcomas. The data regarding prolonged gemcitabine infusions suggest improved activity that was predicted based on prolonged intracellular gemcitabine levels. Because of these data, the prolonged infusion schedule should be used. In addition, because of the paucity of effective agents, consideration of clinical trial participation for patients with newly diagnosed metastatic disease is appropriate, particularly in chemotherapy-insensitive histologies. The role of the newer agents (eg, ecteinascidin-743, epothilones, and mammalian target of rapamycin) is undefined. Ecteinascidin-743 has been the most extensively tested agent, and its ability to slow growth kinetics of a tumor and stabilize it clinically is intriguing. Data regarding the response to BMS-247550 will be published shortly and will help define the further role of epothilones in this disease. There is a preclinical rationale that makes the mammalian target of rapamycin inhibitors attractive for the treatment of muscle-derived neoplasms. In addition, there are cell-line data suggesting activity in rhabdomyosarcoma. These agents are being tested in adult STS and will likely be tested in pediatric histologies when there are more safety data available in that population. SU11248 will continue to be tested in patients refractory to imatinib mesylate and may well prove to be another active agent for patients with gastrointestinal stromal tumors. As depicted by the analysis of gemcitabine efficacy, agents with activity in a subgroup of STS may be overlooked by the "come one come all" approach to clinical trials in STS. Identifying key targets in specific STS will be helpful in the testing of newer molecularly targeted agents. Biologic differences will support histology-specific trials to better understand the activity of an agent in a specific disease site or specifically target a biologic pathway with relevance to the malignant potential of the disease. For future clinical trials in STS to achieve the goal of histology-specific trials, cooperative group and multi-institutional trials will be required to obtain the appropriate patients with these rare histologies. It will also be increasingly important to be committed to obtaining tumor tissue in these patients to validate hypotheses regarding tumor biology and the effectiveness of therapeutic agents.
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PMID:New therapeutic strategies for soft tissue sarcomas. 1458 25

A 65-year-old male patient was admitted to our hospital with continuous left hypochondralgia. CT scanning revealed an avascular tumor at the tail of the pancreas measuring 53 x 52 x 50 mm. Preoperative serum CEA was 198 ng/ml. During laparotomy, the tumor was deemed unresectable and insertion of a catheter in the splenic artery was carried out for postoperative arterial chemotherapy. Gemcitabine (GEM) was administered 1,000 mg 3 times in 2 months via the subcutaneous port connected to the catheter. Slight nausea was the only adverse effect. Decrease in tumor size was observed and serum CEA level dropped to 16.7 ng/ml. In the outpatient setting, 500 mg of GEM was administered several times. One year has passed since the initial treatment, and while the tumor is slowly enlarging, no liver metastasis has been observed. Oral NSAID has controlled the persisting back pain. In conclusion, arterial chemotherapy using GEM for advanced pancreatic cancer may be beneficial for patients.
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PMID:[Gemcitabine infusion via splenic artery for advanced pancreatic cancer]. 1461 95

Pancreatic cancer has one of the worst prognosis of any malignant disease. The National Registry of Japan Pancreas Society has reported that only 13% of patients achieve 5 years survival after surgical resection. The vast majority of patients present with metastatic or unresectable disease. Gemcitabine (GEM) has replaced 5-fluorouracil (5-FU)-based chemotherapy as the standard of care. GEM first generated improvements in symptom control and survival in advanced disease, spurring further research. For locally advanced disease, most recent studies have incorporated GEM into combined-modality therapy. However, subsequent trials have not demonstrated that combinations of other agents with GEM extend clinical benefits yet. Similarly, in surgically resectable disease, current trials are incorporating GEM into adjuvant therapy. According to several clinical trials it has been demonstrated that improvements in locoregional control and survival may be achieved when chemotherapy using 5-FU is added to radiation for locally advanced pancreatic cancer. The new regimen for locally advanced disease has demonstrated that the better outcome is expected by chemoradiation therapy with 5-FU followed by GEM treatment. Furthermore, one of the patients showed the significant regression of pancreas tumor, resulting in the successful surgical resection. In order to develop chemotherapy for pancreatic cancer, we are analyzing mRNA expression of pancreas cancer cell lines and examined their resistant against to GEM. One of the genes is demonstrated to be a responsible for drug sensitivity by clustering analysis.
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PMID:[Chemotherapy for pancreatic cancer]. 1465 Sep 57

Taxotere as a 'stabilizing antitubuline' and a second-generation Taxan has anti-tumor activity in a variety of solid neoplasms. In NSCLC Taxotere has shown encouraging response rates across a range of phase-II studies, and phase-III trials have confirmed its effectiveness in pretreated and chemotherapy-naive patients. Single agent Taxotere has shown that it can significantly improve both survival and quality of life when compared to either best supportive care or standard chemotherapy in previously treated patients. Therefore, it is considered standard for NSCLC second-line chemotherapy. Taxotere has also been evaluated in combination with platinum-compounds and non-platinum-based drugs for first-line treatment of NSCLC. The results recently published from a phase-III registration trial (TAX 326) have shown that the overall survival among patients randomized to receive Taxotere/Cisplatin was better than that among patients treated with Vinorelbin/Cisplatin and similar compared to Vinorelbin/Cisplatin for those patients who received Taxotere/Carboplatin. Given concomitantly or sequentially with non-platinum-based compounds (i.e. Gemcitabine, Vinorelbine) Taxotere has also shown promising activity in randomized studies and may offer advantages for patients not eligible to receive platinum-based compounds.
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PMID:[Docetaxel (Taxotere) as first-line therapy of advanced non-small cell lung cancer (NSCLC)]. 1471 39

Small-cell lung cancer (SCLC) accounts for 20%-25% of all new cases of lung cancer and represents the sixth most commonly diagnosed cancer in the United States. Given the tumor's systemic nature and chemoresponsiveness, chemotherapy has become the cornerstone of its management. Chemotherapy significantly prolongs survival; however, most of the patients still die within 2 years of diagnosis. Combination chemotherapy represents the treatment of choice for this disease. In the United States, cisplatin/etoposide is the regimen most frequently used for the first-line therapy of SCLC patients because of its better therapeutic index. Upon recurrence, topotecan is the Food and Drug Administration-approved treatment based on a phase III trial that showed no statistically significant differences in survival or response for topotecan compared with CAV (cyclophosphamide/doxorubicin/vincristine) but a better disease-related symptom improvement compared to baseline favoring the topoisomerase I inhibitor. Newer agents, with novel mechanisms of action, have shown activity against SCLC and are being tested in many different combinations. Among these agents, gemcitabine has attractive mechanisms of action and toxicity profile. Gemcitabine is a pyrimidine nucleoside antimetabolite, analogue to cytosine arabinoside, which through incorporation into the DNA leads to inhibition of DNA synthesis and cytotoxicity. As a single agent, gemcitabine has modest activity against SCLC. However, like with many other drugs, response rates improve when gemcitabine is used in combination regimens. Phase II and III studies of combinations with classic drugs for the management of SCLC patients such as cisplatin and/or etoposide and gemcitabine demonstrate comparable results to those of standard therapies. The gemcitabine/paclitaxel and gemcitabine/topoisomerase I inhibitor combinations are also of great interest, and preliminary results in previously treated patients are promising. The proper role of gemcitabine in the treatment of patients with SCLC awaits future testing in randomized phase III trials.
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PMID:New agents in the treatment of small-cell lung cancer: focus on gemcitabine. 1472 Mar 38


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